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New kidney cancer treatment guidelines, 2009
I. Epidemiology and Etiology
Second, the pathological
Third, the clinical manifestations
Sixth, surgical complications
Seven prognostic factors
VIII, diagnosis and treatment of hereditary renal cell carcinoma First Hospital of Shanxi Medical University, Department of Urology Liu Shangying
Nine, followed up
Asymptomatic renal cell carcinoma (incidental renal cell carcinomas): no clinical symptoms or signs, from B-or CT examination revealed a renal cell carcinoma, previous known as "incidental renal cancer."
Vice-tumor syndrome (paraneoplastic syndromes): occurs in primary tumors and metastatic lesions than lesions caused by tumor syndrome, previous known as the "kidney renal manifestations."
Limitations of renal cell carcinoma (localized renal cell carcinoma): 2002 edition of AJCC's TNM staging of T1-T2N0M0 renal cell carcinoma, clinical stage â… , â…¡, habit known as "early kidney cancer."
Locally advanced renal cell carcinoma (locally advanced renal cell carcinoma): associated with regional lymph node metastasis and (or) renal vein tumor thrombus, or (and) the inferior vena cava tumor thrombus (or) adrenal metastasis or tumor invasion or perirenal fat tissue (and) the renal sinus fat (but not more than perirenal fascia) or distant metastasis of renal cell carcinoma, 2002 AJCC clinical stage â…¢, previous known as the "locally advanced renal cell carcinoma."
Metastatic renal cell carcinoma (metastatic renal cell carcinoma): 2002 edition AJCC clinical stage â…£, renal cell carcinoma, including T4N0M0 renal cell.
Nephron sparing surgery (nephron-sparing surgery, NSS): general term retention kidney surgery, including partial nephrectomy, wedge resection of kidney, kidney tumor enucleation and so on.
Minimally invasive (minimally invasive treatment): the literature on minimally invasive treatment is not strictly defined, this guide will radiofrequency ablation, high intensity focused ultrasound, cryoablation areas classified as minimally invasive treatment. The laparoscopic radical nephrectomy or NSS, and the scope of the removal of tissue with open surgery, this guide is not to classify it as a minimally invasive treatment areas.
Renal cell carcinoma (renal cell carcinoma, RCC) is originated in the renal tubular epithelium of urinary system cancer, also called renal adenocarcinoma, referred to as kidney cancer, kidney cancer accounts for 80% to 90%. Including the origin of the urinary tubules in the different parts of the various subtypes of renal cell carcinoma, but not from the kidney and renal pelvis epithelial mesenchymal systems of various tumors.
I. Epidemiology and Etiology
Adult malignant renal cell carcinoma accounts for about 2% to 3%, countries or regions the incidence of different countries with a high incidence in developing countries . Various regions of the incidence of re
Cause of kidney cancer is unknown. The incidence and genetics, smoking , obesity , hypertension and antihypertensive treatment  and other relevant (level of evidence â…¡ a), hereditary kidney cancer or familial kidney cancer accounts for 2 to the total number of renal cell carcinoma 4% [1-3, 10]. Not smoking and avoiding obesity is an important method to prevent occurrence of renal cell carcinoma (recommended grade B). Non-genetic factors in sporadic kidney cancer called renal cell carcinoma.
Second, the pathological
Most renal cell carcinoma in the side of the kidney, often for a single tumor, 10% to 20% for multiple lesions, multiple lesions common in cases of hereditary papillary renal cancer and renal patients . Kidney tumors in the upper and lower poles, large differences in tumor size, the average diameter of 7cm, pseudocapsule often separated and the surrounding renal tissue. Those with bilateral disease (successively or simultaneously) of sporadic renal cell carcinoma accounts for only 2% to 4% .
Over the past 20 years, WHO launched a total of 3 version of the standard classification of renal tumors, previously the most widely used WHO classification in 1981 (1st edition), this classification of renal cell carcinoma will be divided into clear cell carcinoma, granular cell carcinoma , papillary adenocarcinoma, sarcomatoid carcinoma, undifferentiated carcinoma 5 pathological type. WHO in 1997, and according to the tumor cell origin and other characteristics of genetically modified skin developed renal tumor classification is essentially  (2), this category will be divided into clear cell renal cell carcinoma (60% ~ 85%), renal papillary like cancer or as addicted to color cell carcinoma (7% ~ 14%), chromophobe cell carcinoma (4% ~ 10%), collecting duct carcinoma (1% -2%) and unclassified renal cell carcinoma (Level of Evidence â…¡ a .) Abolition of the traditional classification of granular cell carcinoma and sarcomatoid carcinoma of type 2. Based on morphological changes of renal papillary adenocarcinoma were divided into type â… and â…¡ type 2 [12,13].
WHO in 1997, 2004 of renal cell carcinoma histological classification has been modified (3rd edition), to retain the original renal cell carcinoma, renal papillary adenocarcinoma (â… and â…¡), chromophobe renal cell carcinoma and unclassified renal cell carcinoma in 4 sub-type, will be further divided into the Bellini collecting duct carcinoma of collecting duct carcinoma and medullary carcinoma, in addition to an increase of multilocular cystic renal cell carcinoma, Xp11 translocation renal cell carcinoma, neuroblastoma with Development of the cancer, mucinous tubular and spindle cell carcinoma type. And the traditional classification of granular cell carcinoma classified as poorly differentiated (high grade) of clear cell carcinoma subtype of the components in sarcomatoid carcinoma of the proportion in the tumor tissue is described. WHO in 2004 recommended the pathological classification of renal cell carcinoma  (recommended grade B).
Iii histological grade
The most commonly used past 1982 Fuhrman four categories . Fuhrman 1997, WHO recommended classification of grade â… , â…¡ merged into one that is well differentiated, â…¢ grade as moderately differentiated, â…£ grade poorly differentiated or undifferentiated. Recommend the use of the RCC into well-differentiated, moderately differentiated, poorly differentiated (undifferentiated) classification criteria  (recommended grade B).
Recommended in 2002 the TNM staging and AJCC staging portfolio (Table -2, -3)  (recommended grade B). In the 2002 AJCC staging evaluation of N stage, the request should include at least the number of detected lymph nodes were removed 8 lymph nodes, lymph node biopsy if the results were negative or only one positive, the number of detected lymph nodes <8, can not be evaluated as N0 or N1. However, if the number of pathological lymph node metastasis identified â‰¥ 2 , N stage is not detecting the impact of number of lymph nodes, identified as N2.
Table -2 2002 AJCC TNM staging renal cell carcinoma
Primary tumor (T)
Unable to assess the primary tumor
Primary tumor was not found
Tumor limited to kidney, the maximum diameter of â‰¤ 7cm
T1a Tumor limited to kidney, maximum tumor diameter â‰¤ 4cm
T1b tumor limited to kidney, 4cm
Tumor limited to kidney, the maximum diameter of> 7cm
Tumor invasion and major veins, adrenal, kidney surrounding tissue, but not more than perirenal fascia
T3a tumors and adrenal invasion or perirenal adipose tissue and (or) renal sinus fat tissue, but not more than perirenal fascia
T3b the naked eye, the tumor invaded the renal vein or renal vein segment branch (including muscle) or the inferior vena cava below the diaphragm
T3c the naked eye, the tumor invaded the diaphragm and inferior vena cava or vena cava wall violations
More than perirenal fascia invasion
Regional lymph nodes (N)
Unable to assess regional lymph node metastasis
No regional lymph node metastasis
A single regional lymph node metastasis
More than one regional lymph node metastasis
Distant metastasis (M)
Distant metastasis can not be assessed
No distant metastasis
Regional lymph nodes, including the kidney: renal hilum lymph nodes, lymph nodes around the superior vena cava, aortic lymph nodes and perirenal retroperitoneal lymph nodes.
Table -3 portfolio in 2002 AJCC staging renal cell carcinoma
Third, the clinical manifestations
Present, past classics hematuria, flank pain, abdominal mass "triad of renal cancer" clinical occurrence rate has been less than 15% of patients with these symptoms is often the time of diagnosis with advanced disease [1,10]. The detection rate of asymptomatic renal cell carcinoma increased year by year, 1995 to 2005 reported in China in the ratio of 13.8% ~ 48.9% [17,18], an average of 33%, 50% reported abroad . 10% to 40% of patients Vice tumor syndrome , manifested as high blood pressure, anemia, weight loss, cachexia, fever, polycythemia, abnormal liver function, hypercalcemia, hyperglycemia, elevated ESR, neuromuscular disease, amyloidosis, galactorrhea syndrome, and abnormal blood coagulation changes. 30% of metastatic renal cell carcinoma can be caused by the metastasis bone pain, fractures, cough, hemoptysis and other symptoms treatment.
Mainly rely on clinical diagnosis of renal imaging. Laboratory as a general condition of patients before, and the prognosis of liver and kidney function evaluation, pathological diagnosis is required.
â’ˆ must include a laboratory project of urea nitrogen, creatinine, liver function, complete blood count, hemoglobin, serum calcium, blood glucose, ESR, alkaline phosphatase and lactate dehydrogenase (recommendation grade C).
â’‰ imaging examination must be included in the project or the B-abdominal Doppler ultrasound, chest X-ray film (positive, lateral), abdominal plain and enhanced CT scan (iodine allergy test was negative, no contraindications related to those.) Abdominal plain and enhanced CT scans and chest X-ray film is the preoperative clinical stage of mainly based on (recommended grade A).
â’Š alternative imaging project KUB: open surgical options for the incision to help; radionuclide renography or IVU examination to testify: No line of enhanced CT scan, who can not evaluate the contralateral kidney; radionuclide bone was Check to testify as: â‘ a corresponding bone symptoms; â‘¡ high alkaline phosphatase; â‘¢ â‰¥ â…¢ clinical stage of patients (level of evidence â… b); chest CT scan evidence: â‘ chest X-ray suspicious nodules; â‘¡ clinical stage â‰¥ â…¢ of the patients (level of evidence â… b); head MRI, CT scan evidence: a headache or a corresponding neurologic symptoms in patients (Level of Evidence â… b); abdominal MRI scan evidence: renal insufficiency, ultrasound or CT Check the tips of the inferior vena cava tumor thrombus in patients (Level of Evidence â… b).
â’‹ conditional region and imaging in patients with selected items have the following inspection equipment with good economic conditions in hospitals and patients can choose the checks. Renal ultrasonography, spiral CT and MRI scans mainly used for the diagnosis and differential diagnosis of renal cell carcinoma; positron emission tomography (positron emission tomography, PET) or PET-CT examination is costly, mainly used for detecting distant metastases and the chemotherapy, cytokine therapy, molecular targeted therapy or radiation therapy assessment.
The checks are not recommended â’Œ renal biopsy and renal angiography in the diagnosis of renal cell carcinoma is limited (level of evidence â…¢ a), is not recommended as a routine examination of patients with renal cell carcinoma. The image is difficult to determine the nature of diagnosis in patients with small tumors, you can choose the line nephron sparing surgery or regular (1 to 3 months) were followed up for inspection. Surgical treatment that can not be advanced renal cancer patients treated with chemotherapy or other treatment before diagnosis, may choose to obtain the pathological diagnosis of renal biopsy. On the need palliative treatment of renal artery embolization or nephron sparing surgery required before the renal blood vessels and tumor vessels of renal conditions may choose to angiography.
Integrated imaging findings were clinical stage (clinical stage grouping, cTNM), according to the preliminary development stages cTNM principle of treatment. Determined based on postoperative histological staging the invasion of range (pathological stage grouping, pTNM) evaluation, such as pTNM staging and cTNM deviation of the results of revision surgery by pTNM staging treatment.
The limitations of the treatment of renal cell i
Surgery is the preferred treatment for renal cell carcinoma limitations. Radical nephrectomy is not recommended adding or expanding regional lymph node dissection  (evidence level Ib, recommendation grade A).
â’ˆ radical nephrectomy is a well recognized method of kidney cancer may be cured [21-23]. The classic radical nephrectomy include: perirenal fascia, perirenal fat, suffering from kidney, ipsilateral adrenal gland, feet from the diaphragm to the bifurcation of the abdominal aorta abdominal aorta or inferior vena cava and iliac lymph nodes above the vessel bifurcation ureter. 40 years of radical nephrectomy using the classical treatment of renal cell carcinoma has undergone some changes in the concept, especially in the surgical removal of the scope of changes (such as the selection of appropriate cases to retain the same side of the implementation of the adrenal radical nephrectomy, nephron sparing surgery) have reached consensus on treatment is no longer a single, open surgery (such as laparoscopic surgery, minimally invasive treatment). Modern point of view, meet the following four conditions can choose to retain the ipsilateral adrenal radical nephrectomy [24-28] (evidence level â…¢ a): â‘ or clinical stage â… Phase â…¡; â‘¡ kidney cancer in the next part; â‘¢ tumor <8cm; â‘£ preoperative CT showed adrenal gland normal. But such cases were found during operation, such as abnormal ipsilateral adrenal gland, ipsilateral adrenal gland should be removed . Radical nephrectomy via open surgery or laparoscopic surgery. Choice of open abdominal surgery or lumbar approach, there is no evidence that the advantages which surgical approach . Radical nephrectomy mortality rate of about 2%, local recurrence rate of 1% to 2% [30-32]. Radical nephrectomy is not recommended routine preoperative renal artery embolization [33-39] (recommended grade B).
â’‰ nephron sparing surgery (nephron sparing surgery, NSS) recommended a variety of indications selected by NSS (recommendation grade B), its efficacy with radical nephrectomy [40-43] (evidence level â…¢ a). NSS renal tumor resection should be away from the edge of 0.5 ~ 1.0cm (level of evidence IIa) [44-46], EAU's "Guide for renal cell carcinoma" in that as long as complete resection of the tumor, the thickness of the edge does not affect the recurrence rate [ 2] (Level of Evidence â…¢ a), select the tumor enucleation is not recommended for treatment of sporadic renal cell carcinoma [46-48]. Gross margin on a complete view of Chaqie surrounding normal kidney tissue of cases, not routine intraoperative frozen biopsy peripheral tissues [49,50]. NSS via open surgery or laparoscopic surgery. Nephron sparing surgery after local recurrence rate from 0 to 10%, while the tumors â‰¤ 4cm rate of local recurrence after surgery 0 to 3% . NSS mortality rate of 1% to 2% .
NSS indications [1,10]: renal cell carcinoma in anatomic or functional solitary kidney, radical nephrectomy would lead to renal insufficiency or in patients with uremia, such as congenital solitary kidney, contralateral renal insufficiency or no function other persons and bilateral renal cell carcinoma.
NSS relative indications [1,10]: there are some healthy contralateral kidney renal diseases, such as kidney stones, chronic pyelonephritis or renal function deterioration may lead to other diseases (such as hypertension, diabetes, renal artery stenosis, etc.) patients.
Indications and relative indications for NSS for renal tumor size, there is no specific limit.
NSS optional indications: clinical stage of T1a (tumor â‰¤ 4cm), kidney around the tumor is located, single kidney cancer, contralateral normal renal function may choose to implement NSS  (evidence level â…¡ b).
â’Š laparoscopic surgical procedures including laparoscopic radical nephrectomy and laparoscopic partial nephrectomy. Into the surgical treatment of intraperitoneal, retroperitoneal, and hand-assisted laparoscopy. Scope and Standards resection with open surgery. Laparoscopic surgery for tumors confined within the renal capsule, without the surrounding tissue invasion and without lymph node metastasis and renal vein tumor thrombus in patients with the limitations of their efficacy and considerable open surgery [53,54] (evidence level â…¢ a). Laparoscopic surgery also has a certain mortality.
â’‹ minimally invasive radiofrequency ablation (radio-frequency ablation, RFA), cryoablation (cryoablation), high-intensity focused ultrasound (high-intensity focused ultrasound, HIFU) can be used not suitable for surgery, cancer treatment for small renal cell carcinoma , there is no evidence-based medicine evidence â… ~ â…¢ grade level findings, long-term efficacy can not be determined, should be strictly in accordance with the indications carefully chosen. 3 this is not recommended as the limitations of minimally invasive treatment of choice for treatment of kidney cancer treatment.
Minimally invasive treatment of indications: not suitable for open surgery, nephron sparing function to be as much as possible, with general anesthesia contraindications, renal insufficiency, tumor largest diameter <4cm and is located in the surrounding renal patients with renal cell [55,56].
â’Œ renal artery embolization for the treatment of patients can not tolerate surgery to relieve symptoms can be used as a palliative treatment. Preoperative renal artery embolization may reduce bleeding and increase the opportunities for radical surgery benefit, but there is no evidence-based medicine evidence â… ~ â…¢ grade. Renal artery embolization can cause puncture site hematoma, infarction after embolization syndrome, acute complications such as pulmonary infarction. Does not recommend routine use of preoperative renal limitations of renal artery embolization.
â’ limitations of adjuvant therapy after surgical treatment of kidney cancer can be recommended no adjuvant treatment program. pT1a surgical treatment of renal cell carcinoma 5-year survival as high as 90% or more, do not use postoperative adjuvant therapy recommended. pT1b ~ pT2 renal cell carcinoma after surgery of 1 to 2 years about 20% to 30% of patients with metastasis [57,58], adjuvant radiotherapy and chemotherapy can reduce the relapse rate and transfer rate, not recommended for routine use after adjuvant radiotherapy and chemotherapy. To be explored effective adjuvant treatment.
Ii the treatment of locally advanced renal cell carcinoma
Preferred treatment for locally advanced renal cell method for radical nephrectomy, whereas lymph node metastasis or vascular tumor emboli to be based on the severity of the patient's physical condition and other factors to choose whether resection. There is no standard adjuvant treatment after surgery.
â’ˆ regional or extended lymph node dissection in early studies advocated doing regional or extended lymph node dissection, and recent study results suggest that extended lymph node dissection of regional or node-negative patients on postoperative tumor stages only to determine the practical significance (level of evidence â… b ); as much associated with lymph node-positive patients with distant metastasis, the joint medical treatment after surgery required, regional or extended lymph node dissection in patients with only a small part of the benefit.
â’‰ renal vein and / or vena cava tumor thrombus in the surgical treatment of the majority of scholars believe that the TNM stage, tumor thrombus length of the vena cava tumor thrombus infiltration of the wall is directly related with prognosis . Recommended in patients with clinical stage T3bN0M0 renal and / or vena cava tumor thrombus removal surgery. CT or MRI is not recommended for scanning suggestive of IVC wall invasion or lymph node metastasis or distant metastasis in patients with this surgery. Renal vein or vena cava tumor thrombus removal surgery mortality rate of about 9%.
Vein tumor there is no uniform classification. Recommended by the United States at the Mayo Medical Center (Mayo Clinic) in the five-category classification method : 0: confined to the renal vein tumor thrombus within; â… grade: invasion of the inferior vena cava tumor thrombus within the renal vein tumor thrombus from the opening to the top â‰¤ 2cm; â…¡ levels: hepatic vein tumor thrombus invasion of inferior vena cava below the level within the renal vein tumor thrombus to the top from the opening> 2cm; â…¢ grade: intrahepatic tumor thrombus growing up to the level of the inferior vena cava, the diaphragm the following; â…£ grade: tumor thrombus invasion of inferior vena cava above the diaphragm.
3. Postoperative adjuvant therapy of locally advanced renal cell carcinoma after radical nephrectomy is no standard adjuvant treatment. Renal cell carcinoma is not sensitive to radiation oncology, radiotherapy alone can not achieve better results. Usually less use of preoperative radiotherapy, surgery is not recommended routinely for tumor bed radiotherapy area, but failed to complete excision of stage â…¢ renal intraoperative or postoperative radiotherapy choice or by reference to the treatment of metastatic renal cell carcinoma.
Iii metastatic renal cell carcinoma (clinical stage â…£) in the treatment of
Metastatic renal cell carcinoma (metastatic renal cell carcinoma, mRCC) to medical treatment should be based, integrated treatment. Mainly surgical adjuvant treatment for metastatic renal cell carcinoma, a very small number of patients obtained by surgery compared with long-term survival.
â‘´ renal surgical treatment of primary lesion: a good state of physical, low-risk factors (see Table -4)  should be preferred in patients with surgical resection of the primary tumor can increase renal IFN-Î± or (and) IL-2 the efficacy of the treatment of metastatic renal cell carcinoma (Evidence level â… b) [62-64]. Cause severe hematuria of renal cancer, pain and other symptoms may choose palliative nephrectomy, renal artery embolization to relieve symptoms and improve quality of life. Metastatic kidney cancer mortality was 2% to 11%.
â‘µ metastases surgical treatment: radical nephrectomy on the isolation of postoperative metastasis and renal cell carcinoma associated with solitary metastasis, patients with good behavior and state can choose surgical treatment. Associated with the transfer of patients, visual and physical condition of patients with kidney surgery at the same time or in phases .
Principle of treatment of bone metastasis renal cell carcinoma: clinical study showed that the transfer of parts caused by the RCC, the bone metastasis accounted for 20% to 25% . The autopsy found that the patients died of RCC bone metastasis was 40% . Associated with renal cell carcinoma bone metastasis and more visceral metastasis and poor prognosis, it is desirable to adopt a comprehensive medical-based treatment most effective treatment of bone metastasis is the surgical removal of metastases. The primary lesions of resectable or has been removed as the primary bone lesion with a single lesion (not associated with other metastatic disease) patients, surgical treatment should be positive. Associated with load-bearing bone metastases in patients with bone fracture risk associated with prophylactic fixation should be carried out to prevent fractures. Pathological fracture has occurred or spinal cord compression symptoms who meet the following three conditions should first select the orthopedic surgery: â‘ expected survival of patients with> 3 months; â‘¡ good physical condition; â‘¢ surgery can improve the quality of life of patients, there help received radiotherapy and chemotherapy and care.
â’‰ medical treatment over the past 20 years, randomized controlled study failed to demonstrate that LAK cells, TIL cells, IFN-Î³ treatment of metastatic renal cell carcinoma effectively. 90 years since the twentieth century, middle and high doses of IFN-Î± or (and) IL-2 has been used as standard first-line metastatic renal cell carcinoma treatment, efficiency is about 15%. A large number of clinical studies, high doses of IFN-Î± on the low, intermediate risk patients with metastatic renal cell carcinoma and effective (level of evidence â… b) [67,68], combined with China's specific conditions, recommended in high-dose IFN-Î± as a treatment for metastatic renal cell carcinoma of basic drugs (recommended grade A). 2006 NCCN, EAU to molecular targeted therapy (sorafenib, sunitinib, Temsirolimus, bevacizumab in combination with interferon-Î±) [69-72] as a metastatic renal cell carcinoma, second-line treatment medication (Level of Evidence â… b).
â‘´ cytokine therapy
July 2004-June 2006, the drug in China, the single source of recombinant human IL-2 (Proleukin) subcutaneous treatment of metastatic renal cell carcinoma Phase â…¢ study , the study is an open, multi-center , non-controlled clinical study. Into the group of 41 patients with pathologically confirmed metastatic renal cell carcinoma patients. The first week of receiving IL-2 9MIU Q12h d1-5, three weeks after 9MIU Q12h d1-2, 9MIU Qd d3-5, repeated after a week off. 5 weeks as a cycle, a total of 2-4 cycles. Toxicity of 5 cases out of group, 36 were evaluable for objective response, CR 0 , PR 7 (19.4%), SD 16 (44.4%), PD 13 cases (36.1%), disease control rate of 63.9%, The median time to progression (progression-free survival, PFS) has not yet arrived, but more than 12 months. Serious adverse reactions (â‰¥ 3 level) rare, mainly for the 1-2 multi-level system with mild to moderate adverse events were fatigue, flu (100%), fever (82.9%), subcutaneous injection site induration (68.3%) rash / desquamation (43.9%), diarrhea (24.4%), vomiting (17.1%), transaminase elevation (39%), elevated serum creatinine (39%), blood urea nitrogen increased (22%), anemia (12.2 %), dyspnea (12.2%), and, most adverse events were reversible. The results show that low-dose IL-2 in the treatment of metastatic renal cell carcinoma of the Chinese and foreign reports have the same effect, and can prolong the survival, mainly mild to moderate adverse reactions, patients can tolerate.
IL-2 recommended dose: 18 MIU / d IH. 5d / W Ã— 5 ~ 8 weeks (recommendation grade B) [73,74]
Recommended therapeutic dose of IFN-Î± (recommended grade A): IFN-Î±: each 9MIU, im, or IH., 3 times / week for 12 weeks. Can be increased gradually from each 3MIU, 1 week each 3MIU, 2 weeks each 6MIU, the first 3 weeks after each 9MIU. Check the blood during treatment 1 week, 1 month check liver function, white blood cell count <3 Ã— 109 / L or abnormal liver function and other serious adverse reactions should be discontinued, to be restored before continuing treatment. If patients can not tolerate each 9MIU dose should be tapered to every 6MIU even every 3MIU.
Although IFN-Î± combined IL-2 therapy can improve the efficiency of mRCC, but can not improve PFS.
â‘µ molecular targeted therapy
April 2006 to August 2007, the conduct of sorafenib in treating Chinese patients with advanced renal cell carcinoma of the safety and efficacy of the study that is open, multi-center, non-controlled clinical study into the group of 62 cases were patients with advanced renal cell carcinoma (received at least one previous systemic therapy), 5 patients withdrew from the study because of side effects, 57 patients were evaluable. The median age was 53 years old, male, 43 cases received sorafenib 400mg bid for at least 2 months. Results CR1 patients (1.75%), PR 11 (19.3%), SD 36 patients (63.16%), disease control rate was 84.21%, median PFS time of 41 weeks, median overall survival (overall survival, OS) is not up. Grade 3-4 toxicities included hand-foot skin reaction (16.1%), diarrhea (6.45%), hypertension (12.9%), leukopenia (3.2%), hyperuricemia (9.7%). The disease control rate (CR PR SD) and foreign sorafenib III randomized double-blind controlled study of (TARGET test) consistent with those reported .
Recommended dosage of sorafenib 400mg bid / day (recommended grade B)
Nearly 2 years of clinical experience domestic: Incremental sorafenib (600mg ~ 800mg bid / day)  or sorafenib (400mg bid) combined IFN-Î± (3MIU im or IH. 5 times a week)  programs can increase the effective treatment of advanced renal cell carcinoma (Evidence level â…¢ b), but related toxicity was higher than sorafenib 400mg bid / day treatment programs.
Primary chemotherapy for the treatment of mRCC drugs gemcitabine (gemcitabine), fluorouracil (5-FU) or capecitabine (Capecitabine), cisplatin (cisplatin), gemcitabine combined with fluorouracil or capecitabine is mainly used to clear cell the main type of mRCC; gemcitabine and cisplatin is mainly used mainly in non-clear cell type of mRCC; if the tumor contains a sarcomatoid component, chemotherapy can be combined with doxorubicin. Chemotherapy efficiency of about 10% to 15%. Chemotherapy combined with IFN-Î± or (and) IL-2 also did not show superiority.
Recommended chemotherapy for metastatic non-clear cell carcinoma as first-line treatment in patients (Level of Evidence â…¢) .
Recommended adoption of a new evaluation standard solid tumors (RECIST)  evaluation of renal cell carcinoma immunotherapy or chemotherapy.
â’Š radiotherapy on local recurrence of the tumor bed, regional or distant lymph node metastasis, bone or lung metastases, palliative radiotherapy for pain relief can be achieved, the purpose of improving the quality of life. Carried out in recent years, stereotactic radiotherapy (Î³ knife, X knife, three-dimensional conformal radiotherapy, intensity modulated radiation therapy) for recurrent or metastatic lesions can play a role in better control, but effective systemic treatment should be based on .
The treatment of renal cell carcinoma principles of brain metastases: Autopsy results showed that patients died of renal cell carcinoma with brain metastasis in 15% , 60% to 75% in patients with brain metastases have clinical signs or symptoms, mainly headache (40% ~ 50%), focal neurological symptoms (30% -40%) and epilepsy (15% -20%), and other signs and symptoms . The treatment of renal cell carcinoma patients with brain metastases should be used in medical therapy combined therapy, but patients with symptoms associated with cerebral edema with corticosteroids should be added; brain metastases associated with other parts of the transfer of patients, hormones and brain radiotherapy is the treatment an important tool. Behavior in good condition, a simple choice for patients with brain metastases from brain surgery (brain metastases â‰¤ 3 unit) or stereotactic radiotherapy (maximum diameter of brain metastases â‰¤ 3 ~ 3.5 cm) or brain surgery combined with radiotherapy .
Sixth, surgical complications
Either open surgery or laparoscopic surgery for renal cell carcinoma are possible bleeding, infection, perirenal organ damage (liver, spleen, pancreas, gastrointestinal tract), pleural damage, pulmonary embolism, renal failure, liver failure , leakage and other complications, should pay attention to the prevention and appropriate treatment. Severe cases can cause death in patients, surgery patients and their families should be informed before the surgical risk and possible complications.
Seven prognostic factors
The prognosis of renal cell carcinoma is staging the most important factor, in addition, histological grade, patient performance status score, symptoms, tumor necrosis is organized, a number of biochemical abnormalities and changes in other factors also associated with the prognosis of renal cell carcinoma . Past that the prognosis of renal cell carcinoma histological type, papillary carcinoma and chromophobe renal cell carcinoma prognosis is better than clear cell carcinoma; renal papillary type â… Type â…¡ better outcome; collecting duct carcinoma prognosis than transparent cell carcinoma of the difference [80-82]. However, a related cell subtypes and prognosis of RCC patients in a multicenter study  showed that with the TNM stage, cancer grade and performance status scores compared to histological subtype was not an independent prognostic factor in tumor stage, grade the same circumstances in outcome between the subtypes there was no significant difference (level of evidence â…¡ a). However, different histological types of mRCC treatment of cytokine response rate is different in patients with clear cell carcinoma type response rate of about 10% to 20%, while papillary carcinoma and chromophobe renal cell carcinoma cell factor treatment difference [82 , 84]. Prognostic factors in metastatic renal cell carcinoma rates in Table 4 .
Table 4 of prognostic factors in metastatic renal cell carcinoma ratings
> 1.5 times the upper limit of normal
Female <11.5g / L male <13g / L
> 10 mg / dL
Primary cancer diagnosis to the start time for medical treatment
â‰¤ 70 minutes
Note: Low risk: 0; in crisis: 1 to 2 risk factors; high risk: â‰¥ 3 a dangerous factor.
Table 5 Physical Status Grading
Karnofsky score (KPS, Percentages)
Zubrod-ECOG-WHO (ZPS, 5 points method)
Normal, asymptomatic, and signs
To carry out normal activities, have mild symptoms and signs
Light-like symptoms, life itself, to engage in light physical activity
Barely normal activities, there are some signs or symptoms
Life can take care of themselves, but can not maintain a normal life and work
Can tolerate the symptoms of cancer, daily living, but during the day and not more than 50% of the time in bed
Most of life can take care of themselves, but occasionally need help
Often need someone to look
Cancer symptoms are severe, more than 5% during the day time in bed, but can get up to stand, some self-care
Life can not take care of themselves in need of special care and assistance
Serious life can not take care of themselves
Seriously ill, requiring hospitalization and active supportive care
Critically, near death
VIII, diagnosis and treatment of hereditary kidney cancer
Hereditary kidney cancer has been defined, including : â‘ VHL syndrome; â‘¡ hereditary papillary renal carcinoma; â‘¢ hereditary leiomyomatosis renal cell carcinoma; â‘£ BHD (Birt-Hogg-Dube) syndrome.
(A) of the diagnostic criteria of hereditary renal cell carcinoma
â‘ age of the sick, the young majority, with / without family history; â‘¡ often bilateral renal tumors, multiple, with radiographic features of renal cell carcinoma; â‘¢ other manifestations of the above syndrome, such as VHL syndrome can be combined into the central nervous system and retinal hemangioblastomas, pancreatic cysts or tumors, adrenal pheochromocytomas, epididymal papillary cystadenoma, renal cysts and other changes; â‘£ test confirmed that the corresponding chromosomes and genetic abnormalities.
(B) the treatment of hereditary kidney cancer
VHL syndrome reported more, other types of hereditary renal cell carcinoma only see a small sample of case reports or case reports. Most of the hereditary renal cell carcinoma with VHL syndrome is similar to the methods and principles.
VHL syndrome, renal cell carcinoma treatment principles: kidney tumor diameter <3cm by watchful waiting, when the tumor diameter â‰¥ 3cm to consider surgery to NSS is preferred, including tumor enucleation.
Nine, followed up
Followed up for the main purpose is to check whether there is recurrence, metastasis, and new tumors. The economy can not be determined, the content and followed up followed up for a reasonable time frame, the competent physician can be combined with the local medical conditions, patient, etc. refer to the following content.
Followed up in the first 4 to 6 weeks after surgery [1,2], the main assessment of kidney function, blood loss, recovery from the situation and the availability of surgical complications. NSS on the lines of 4 to 6 weeks after surgery in patients with renal CT scan, to understand renal morphological changes for future review to do comparison purposes .
General followed up include: â‘ history taking; â‘¡ physical examination; â‘¢ blood and blood biochemical examination: liver, kidney and blood of preoperative biochemical abnormalities, such as abnormal preoperative serum alkaline phosphatase, usually require further review as recurrent or persistent abnormalities of alkaline phosphatase is usually suggestive of distant metastasis or residual tumor. If there is abnormal increase of alkaline phosphatase, or (and) with bone metastasis symptoms such as pain, the need for bone scan. Elevated alkaline phosphatase may also be liver tumor syndrome or vice performance; â‘£ chest X-ray films (positive, lateral). Chest X-ray examination revealed abnormalities in patients with chest CT scan suggested; â‘¤ abdominal ultrasound. Abdominal ultrasound in patients with abnormal, NSS, and T3 ~ T4 need of kidney cancer patients after surgery abdominal CT scan can be 1 every 6 months for 2 years, since, as the case may be.
Phases of renal cell carcinoma follow-up time: â‘ T1 ~ T2: every 3 to 6 months follow-up time for 3 years, after a year follow-up time; â‘¡ T3 ~ T4: every 3 months follow-up time for 2 years, 3 years, every 6 months follow-up Once, after one year follow-up; â‘¢ VHL syndrome after treatment: should be conducted every 6 months, abdominal and head CT scan 1. Once a year the central nervous system MRI, measurement of urinary catecholamines, eye and hearing tests.
Epidemiology and Etiology
Renal cell carcinoma is derived from renal tubular epithelial urinary system malignancies.
Cause of kidney cancer is unknown. A small number of kidney cancer and genetic factors, known as hereditary kidney cancer or familial kidney cancer. Non-genetic factors in sporadic kidney cancer called renal cell carcinoma.
Pathology Department of Urology, Fuzhou General Hospital of Nanjing Military Region, Cheng Kai
First, in general: often pseudocapsule apart with the surrounding renal tissue. Hereditary kidney cancer is usually manifested bilateral, multiple tumors.
Second, classification: recommended WHO 1997 origin and genetic basis of tumor cell characteristics such as the development of renal changes in skin tumor classification is essentially
Clear cell carcinoma, papillary renal cell carcinoma or as addicted to color cell carcinoma, chromophobe cell carcinoma, collecting duct carcinoma and unclassified renal cell carcinoma.
Third, histological grade: Recommended by the kidney is divided into well differentiated, moderately differentiated, poorly differentiated (late differentiation) classification standards.
Four phases: Recommended by 2002 AJCC TNM stage and clinical stage of.
Past classic hematuria, flank pain, abdominal mass "triad of renal cell carcinoma", these patients often have advanced the time of diagnosis. Detection rate of asymptomatic renal cell carcinoma increased year by year.
Vice-tumor syndrome: the performance of high blood pressure, anemia, weight loss, cachexia, fever, polycythemia, abnormal liver function, hypercalcemia, hyperglycemia, elevated ESR, neuromuscular disease, amyloidosis, galactorrhea syndrome, abnormal changes in blood coagulation mechanism.
Metastatic renal cell carcinoma: tumor metastasis may be caused by the bone pain, fractures, cough, hemoptysis and other symptoms treatment.
Mainly rely on clinical diagnosis of kidney cancer imaging, diagnosis need to depend on pathological examination.
Abdominal plain and enhanced CT scans and chest X-ray film is the main preoperative clinical stage basis.
Biopsy and renal angiography in the diagnosis of kidney cancer are limited, is not recommended as a routine examination.
First, the limitations of the treatment of renal cell carcinoma
Surgery is the preferred treatment for renal cell carcinoma limitations.
1. Radical nephrectomy: is the only recognized method of kidney cancer may be cured. Radical nephrectomy is not recommended plus regional or extended lymph node dissection.
The classic radical nephrectomy include: perirenal fascia, perirenal fat, suffering from kidney, ipsilateral adrenal gland, renal and iliac lymph vessels decentralization door over the ureter.
Modern point of view: If I or â…¡ clinical stage of the tumor in the kidney, the lower part, tumor <8cm, preoperative CT showed normal adrenal glands, adrenal gland can choose to keep the same side of radical nephrectomy.
2. Nephron sparing surgery (Nephron sparing surgery, NSS):
NSS renal tumor resection should be away from the edge of 0.5-1.0 cm.
NSS indications: renal cell carcinoma of solitary kidney, contralateral non-functional renal insufficiency or those with bilateral renal cell carcinoma and so on.
Relative indications for NSS: there are some healthy contralateral kidney renal diseases, such as kidney stones, chronic pyelonephritis or renal function deterioration may lead to other diseases (such as hypertension, diabetes, renal arteries narrow, etc.) patients.
Indications and relative indications for NSS on the tumor size is no specific limit.
NSS optional indications: clinical stage of T1a (tumor â‰¤ 4cm), kidney around the tumor is located, asymptomatic solitary kidney, contralateral normal renal function can choose the implementation of NSS.
3. Laparoscopic surgery:
Surgical procedures include: laparoscopic radical nephrectomy and laparoscopic partial nephrectomy.
Surgical ways: divided into intraperitoneal, retroperitoneal, and hand-assisted laparoscopy.
For laparoscopic surgery: tumor confined within the renal capsule, without the surrounding tissue invasion and without lymph node metastasis and renal vein tumor thrombus limitations.
4. Minimally invasive treatment: radiofrequency ablation, high intensity focused ultrasound, cryoablation of renal cell carcinoma in the clinical research stage, surgical treatment is not recommended as the preferred treatment.
5. Renal artery embolization:
Preoperative renal artery embolization may reduce bleeding and increase the opportunities for radical surgery benefit, but there is no evidence-based medical evidence.
Renal artery embolization can cause puncture site hematoma, infarction after embolization syndrome, complications such as acute pulmonary embolism. Before surgery is not recommended for routine use.
6. Adjuvant therapy:
pTla surgical treatment of renal cell carcinoma 5-year survival as high as 90% or more, do not use postoperative adjuvant therapy recommended.
pTlb-pT2 1-2 years after surgery of renal cell carcinoma about 20% -30% of patients with metastasis. Not recommended for routine use of adjuvant postoperative radiotherapy and chemotherapy.
Second, the treatment of locally advanced renal cell carcinoma
Preferred treatment for locally advanced renal cell method for radical nephrectomy. Postoperative patients with residual tumor, suggested that the immune deoxycytidine treatment or fluoride (trade name gemcitabine, key selection) based chemotherapy or (and) radiation .
1. Lymph node dissection:
For stage â…¢, â…£ patients with renal cell carcinoma lymph nodes, the proposed removal of the lymph nodes more easily in patients with radical nephrectomy swollen lymph node dissection.
2. Inferior vena cava tumor thrombus in the surgical treatment of:
Most scholars believe that the TNM stage, tumor thrombus length, infiltration of vena cava tumor thrombus is directly related to the wall and prognosis.
Proposed clinical stage T3bN0M0, in good condition and behavior of patients with inferior vena cava tumor thrombus removal surgery. CT or MRI is not recommended for scanning suggestive of IVC wall invasion or lymph node metastasis or distant metastasis in patients with this surgery.
Vein tumor there is no uniform classification. Recommended by the United States at the Mayo Medical Center (Mayo Clinic) in the five classifications:
0: confined to the renal vein tumor thrombus within;
Class I: tumor thrombus in the inferior vena cava, renal vein tumor thrombus to the top from the opening â‰¤ 2 cm;
Grade â…¡: hepatic vein tumor thrombus in the inferior vena cava below the level within the renal vein tumor thrombus from the top opening> 2cm;
Grade â…¢: tumor thrombus in the inferior vena cava in the liver, diaphragm following;
Grade â…£: tumor thrombus in the inferior vena cava above the diaphragm.
3. Adjuvant therapy:
There is no standard adjuvant therapy, adjuvant IFN-Î± or / and IL-2 treatment-related research is under way, there is no conclusion. Autologous tumor vaccine.
Renal cell carcinoma is not sensitive to radiation of the tumor.
Third, metastatic renal cell carcinoma (clinical stage IV) in the treatment of
Based, integrated with the medical treatment.
1. Surgical treatment:
Primary tumor resection can improve renal IFN-Î± or (and) IL-2 treatment of metastatic renal cell carcinoma patients.
Radical nephrectomy for the isolation of postoperative metastasis and renal cell carcinoma associated with solitary metastasis, good performance status, low-risk patients may choose surgery.
Of renal tumors induced hematuria, pain and other symptoms may choose palliative nephrectomy, renal artery embolization to relieve symptoms and improve quality of life.
2. Medical treatment:
Randomized controlled study can not prove that LAK cells, TIL cells, IFN-Î³ treatment of metastatic renal cell carcinoma effectively.
At present IFN-Î± or (and) IL-2 as first-line treatment of metastatic renal cell carcinoma treatment, efficiency is about 15%.
Commonly used chemotherapy drugs can not be determined (either alone or in combination) in metastatic renal cell carcinoma patients.
Recommended adoption of a new evaluation standard solid tumors (RECIST) Evaluation of renal cell carcinoma immunotherapy or chemotherapy.
3. Radiotherapy: recurrence of the tumor bed on local, regional or distant lymph node metastasis, bone or lung metastases, palliative radiotherapy for pain relief can be achieved, the purpose of improving the quality of life.
The prognosis of renal cell carcinoma is staging the most important factor, followed by histological type.
Papillary renal cell carcinoma and chromophobe cell carcinoma prognosis is better than clear cell carcinoma; collecting duct carcinoma worse prognosis than clear cell carcinoma.
Diagnosis and treatment of hereditary kidney cancer
Hereditary kidney cancer has been defined, including:
â‘ VHL syndrome,
â‘¡ hereditary papillary renal cell carcinoma,
â‘¢ hereditary leiomyomatosis renal cell carcinoma,
â‘£ BHD (Birt-Hogg-Dube) syndrome.
First, the genetic diagnosis of RCC points:
â‘ age of the sick, the young majority, with / without family history;
â‘¡ often bilateral renal tumors, multiple, with radiographic features of renal cell carcinoma.
â‘¢ other manifestations of the above syndrome, such as VHL syndrome can be merged into the central nervous system and retinal hemangioblastomas, pancreatic cysts or tumors, adrenal pheochromocytomas, epididymal papillary cystadenoma, renal cysts and other changes.
â‘£ assays confirmed the corresponding chromosomes and genetic abnormalities.
Second, the treatment of hereditary kidney cancer
VHL syndrome, renal cell carcinoma treatment principles: kidney tumor diameter <3cm by watchful waiting, when the tumor diameter â‰¥ 3cm to consider surgery to NSS is preferred, including tumor enucleation.
With the diagnosis
Followed up in the first 4 to 6 weeks after surgery, the main assessment of kidney function, blood loss, recovery from the situation and the availability of surgical complications.
General followed up the contents:
â‘ history taking.
â‘¡ medical examination.
â‘¢ blood and blood biochemical examination: liver, kidney and blood of preoperative biochemical abnormalities, recurrent or persistent abnormalities of alkaline phosphatase is usually suggestive of distant metastasis or residual tumor. May also be liver tumor syndrome or vice performance.
â‘£ chest X-ray films (positive, lateral). Chest X-ray examination revealed abnormalities in patients with chest CT scan suggested.
â‘¤ abdominal ultrasound. Abdominal ultrasound in patients with abnormal, NSS, and T3-T4 patients after surgery of renal cell carcinoma abdominal CT scan must be 1 every 6 months for 2 years, since, as the case may be.
The follow-up period of renal cell carcinoma:
â‘ T1-T2: follow-up once every 3-6 months for 3 years, were followed up 1 year later.
â‘¡ T3-T4: follow-up once every 3 months for 2 years, 3 years of follow-up every 6 months, 1, later followed up once a year.
â‘¢ VHL syndrome after treatment: should be conducted every 6 months, abdominal and head CT scan 1. 1 each year the central nervous system MRI, measurement of urinary catecholamines, eye and hearing tests.
When the type of renal cell carcinoma does not belong to the type of the foregoing, it will not fall into the classification of renal cell carcinoma. In surgical cases, these tumors accounted for 4% to 5%. As the performance of this type of tumor and genetic characteristics of diversity, therefore, can not narrow the definition of underground. Sometimes non-epithelial components of the sarcoma-like structure, to produce mucus, mixed epithelial and stromal components, and does not recognize the cell types included in the unclassified renal cell carcinoma. Sarcomatoid change has been classified can be found in all types of renal cell carcinoma, and mucosa of the urinary tract occurred in the renal pelvis carcinoma. Because there is no evidence that sarcomatoid renal cell carcinoma from the start, therefore, can not be regarded as an independent type, but should be considered a sarcoma-like structure in the poorly differentiated carcinoma in which part. Occasional sarcomatoid tumor growth more than its original composition cancer, but does not recognize the original tumor type, this time, it could be classified as unclassified renal cell carcinoma. Metanephric adenoma and metanephric adenofibroma (metanephric adenoma and metanephric adenofibroma)ã€‘ ã€after the definition of renal adenoma is a wealth of epithelial tumor cells, tumor cells of small and consistent, showing embryo-like. ã€‘ ã€Epidemiology of renal adenoma occurs in children and adults, the most common in 50 to 60 years, more common in women, men and women the incidence rate of 1:2. Metanephric adenofibroma of patients aged 5 months to 36 years, mean 30 months, male and female incidence rate of 2:1. There was 1 case of metanephric adenoma (metanephric adenosarcoma) appears sarcoma components. ã€ã€‘ Approximately 50% of the clinical features of metanephric adenoma in patients with polycythemia because of abdominal pain of ribs or season, mass, or hematuria was found. Prodromal symptoms include polycythemia, or hematuria. Arroyo number of other reported cases of renal Wilms tumor and the occurrence of renal cell carcinoma after kidney adenofibroma related. More than 1 patient had local metastases, but no further. ã€‘ ã€Generally see a great difference in adenoma size, the common diameter 30 ~ 60mm, rarely multifocal. Typical tumor boundary were known, but no capsule, section can be gray, brown, yellow, soft or hard texture. Common spotty hemorrhage and necrosis, about 20% of the tumor calcification, 10% of the tumor with small cysts. Metanephric adenofibroma in solid brown, some cysts, the tumor border is not clear. Histopathologyã€‘ ã€tumor cells are very abundant, closely arranged. Small tumor cell line, rounded alveolar arrangement, like embryonic cells. The acini and acinar cavity is very small, at low magnification is often mistaken for tumor cells were arranged in solid sheets. Common and long branching tubular structure of staghorn. 70% to 80% of the tumor stromal hyalinization, and focal scar-like ossification students. About 50% of the tumors had papillary structures, showing that small capsule with thick prominent nipple, it seems immature glomeruli. Gravel common, and sometimes the number can be many. Tumor with clear boundary and no pseudocapsule. Renal adenoma cell morphology after a single, nuclear small and consistent, the nucleus slightly larger than lymphocytes, round or oval, stained Zhixi Ni, no nucleoli, or nucleoli was not obvious. Scarce cytoplasm, pale staining, mitotic no or rare. Metanephric adenofibroma sheet seen in the rich medium and after spindle cell renal adenomas in the same epithelial nodules. Spindle cells, including fibroblast-like cells, lightly stained eosinophilic cytoplasm, oval or spindle-shaped nucleus, the
ã€— ã€–Phenotype of renal adenoma after the results of immunohistochemistry and diverse. It is reported that CK and vimentin positive. Common WT1 nuclear positive. EMA and CK7 often negative, CD57 positive. Metanephric adenofibroma regular interstitial CD34 positive. Adenomatous component and after the results of immunohistochemistry of renal adenomas similar.