| Background:Colorectal cancer, which generally referred to the colon and rectal cancer, which includes the lesions of ascending colon, transverse colon descending colon and sigmoid colon and rectal epithelial malignant tumours. According to the previous reports, the incidence of colorectal cancer is rectum, sigmoid colon, cecum, ascending colon, descending colon and transverse colon from high to low. In the resent years, we found that, the occurrence of right-side colon proximally has become more and more common. The etiology of colorectal cancer is unknown. At present, the eating habits, genetic, environmental factors, etc. can all be the risk factor of colorectal cancer. Generally speaking, the clinical classification and staging of colorectal cancer always refers to the UICC guideline. In the latest UICC guideline, the pathology classification of colorectal cancer is mainly based on infiltration depth (T stage), lymph node metastasis (N staging) and whether or not combined with a distal metastasis (M).The final goal of tumor staging is to determine the range of the tumor and the possibility of prognosis and provide a direction of treatment. The staging of colorectal cancer is based on the pathological tissue specimens and pathological examination. At present, the criteria of colorectal cancer is generally recognized as the TNM staging criteria and the modified DUKES staging established by AJCC and UICC. In the TNM staging, ???:primary tumor (T) staging:Tx:the primary tumors cannot be estimated;T0:no evidence of primary tumor; Tis:carcinoma in situ:intraepithelial carcinoma or mucous membrane who doesn't penetrate through the mucosal muscularis and submucosa; T1:the tumor invades to the submucosa;T2:tumor invades the inherent intestinal wall and get to the muscle layer;T3: tumor invade through and invades to the muscularis propria subserosal, or serosal layer from the primary lesion of the colon, rectum and tissue adjacents to the tumor; T4:the tumor has penetrated through the peritoneal or directly into other viscera*.(note:* if tumor adhere to other organs (including other segment of colon and rectum) is seemed as T4; if no tumor cell was found under microscopy, it was seemed as pT3; vascular and lymphatic invasion can be made use of V and L. Stage ?:lymph node metastasis (N) stage:Nx:The regional lymph node cannot be estimated;NO:No regional lymphatic metastasis was found;N1:1?3 lymph node metastasis was found;N2:four or more lymph node metastasis. Distant metastases (M) stage.M0:without distant metastases; M1: distant metastasis.In China, the colorectal cancer was divided into early, middle, and late stage, according to the degree of phase ?, ?, ?, ?. In the later of above phases, among them, it also seemed as the advanced colorectal cancer. In mid-late stage, the patients always has a distant metastasis, and thus become metastatic colorectal cancer (mCRC).But this installment method does not guide the clinical diagnosis, surgery and it is just a popular method to colorectal cancer staging. It is generally believed that the prognosis of patients with metastatic colorectal cancer is poor. The 5 years of survival rate is only 5%, and the prognosis has relationship with the position, organs.From the clinical characteristics of metastatic colorectal cancer, the clinical significance is that it can provide an option for doctors to choose the individual chemotherapy regimens according to the degree of pathological types and metastasis. Established on the basis of previous research, in this study, we combined with some of the problems that were encountered in clinical practice, such as the main parts, pathological type and organs of metastasic colorectal cancer in Chinese. By colorectal endoscopic examination, abdominal ultrasound examination, tumor markers and other clinical and laboratory examination, pathological results and so on, a comprehensive diagnosis of metastatic colorectal cancer patients can be made and a statistical analysis and comprehensive judgement based on all of the variety of clinical data.Methods:We prospectively collected 142 mCRC patients diagnosed by clinical examination, imaging examination, laboratory examination, pathologic diagnosis. Based on the collection of clinical data, including age, gender, height, weight, BMI, pathology classification stage, metastasis, as well as the RBC, hemoglobin, etc., a preliminary understanding of clinical features of patients with metastatic colorectal cancer in China was expected. On this basis, through the multiple linear relationship analysis, we expect to find the influencing factors and the correlation between them.Results:in 142 Chinese patients with metastatic colorectal cancer, we found that there are 47 cases with liver metastases,8 cases with lymph node metastases,15 patients with liver metastasis and lymph node metastasis, and metastasis in other organs were found in the remaining 72 cases. According to the pathological results of the 142 patients, 98 (98/142) cases of them is adenocarcinoma, and in histological types,15 cases were mucinous carcinoma and the undifferentiated carcinoma was found in 29 cases. In 142 patients with metastatic colorectal cancer, the colorectal cancer was found in 33 (33/142) cases, and 87 (87/142) cases of them was left colon cancer, and 22 cases of them was right colon cancer (22/142);In the left-colon cancer,51 (51/87) of them is diagnosed as adenocarcinoma,20 (20/51) of them is mucinous carcinoma, and 16 cases of undifferentiated carcinoma (16/51) cases; in patients with right-colon cancer,16 cases (16/51) were adenocarcinoma, and 4 (4/22) of them is mucinous carcinoma,2 (2/22) of them were undifferentiated carcinoma; In patients with colorectal cancer, adenocarcinoma was found in 28 cases of them, and 2 cases of squamous cell carcinoma, 3 cases of mucous cell carcinoma, the Fisher test was used to statistical analysis, but no significant difference was found between them (P> 0.05)Furthermore, a questionnaire survey was conducted among the patients. In all of the 142 patients, postoperative recurrence was found in 53 cases of them, left colon cancer was found in 41 cases of them, and rectal cancer was found in 12 cases of them. All the cases of metastatic right colon cancer were diagnosed primarily. A COX regression model was used to analyze the various factors that the BMI, TNM staging are probably to be the independent factors affecting the OS (P< 0.01).Conclusion:1. The main pathological type is adenocarcinoma in metastatic colorectal cancer patients in China, and the liver metastasis is the most common.2. In patients with metastatic colorectal cancer, left colon cancer is predominal, but the pathological classification is given priority to adenocarcinoma in Chinese.3. BMI and TNM staging is probably to be the independent factors affecting the CEA(P<0.01) according to the COX regression models.A multi-center randomized phase II clinical study of bevacizumab plus irinotecan,5-fluorouracil, and leucovorin (FOLFIRI) compared with FOLFIRI alone as second-line treatment for Chinese patients with metastatic colorectal cancerBackground:In the mCRC patients with a clear pathological staging.the methods of treatment has been transfered from a basic treatment to an individual one.However,before the chemotherapy,an general evaluation of mCRC patients should be done to conform the necessity of chemotherapy,the tolerance of surgery and aneathesia,whether combined with other disease like heart disease or others,and all the possibilities that may happen during the operation.In the treatment of colorectal cancer,an operation is an option in treating the I and II stage of colorectal cancer.The classical treatment of colorectal cancer is surgery whose name is "Total mesorectum excision" or TME,which includes(1)excision of rectum and the surounding mesentary.(2)excision of the surounding lymphonodes.The goal of the operation is to reduce the possibility of a metastatic disease.At present,it has been reported in many reports that the distance between the edge of excision and the tumor should not be less than 1mm.If it is less than lmm,the risk of replase and metastatis will increase.What's more,if the tumor penetrate the mesentary,the surounding lymphonodes should be excised widely.If the tumor penetrates the mesorectum, the corresponding lymph node cleaning range should also be conditionally increase.Chemotherapy can achieve a relatively good efficiency in mCRC patients.At present, most of the mCRC patients can be treated with chemotherapy clinically.But a comprehensive evaluation should be further made in mCRC patients.If the general condition of metastatic colorectal cancer patients was optimal, the metastatisis was limited in pelvic cavity and the distal gastrointestinal tract.Generally, a combination of surgical and postoperative adjuvant chemotherapy was used.But in most of the patients with distant metastases, due to a long history, the cachexia gastrointestinal bleeding, defecate occult blood, lower hemoglobin, always be observed.As a big trauma to these patients, it is believed that the treatment for metastatic colorectal cancer should be given priority to the adjuvant therapy.Pilar suggested that, a necessary evaluation should be done for patients without metastasis.At present,6 kinds of chemotherapy drugs were mainly used in clinical practice:Alkylating agent:cyclophosphamide(CTX) and isophosphamide (IFO), were used in the chemotherapy of breast cancer;(2) antibiotic agents:doxorubicin(DOX),Epirubicin (EPI), pirarubicin(THP), pingyangmycin(PYM), etc.By blocking DNA synthesis and transcription,antibiotic medicines are widely applied to a variety of tissues and organs in tumor treatment.(3) (3) vegetable alkaloid:vincristine (VCR), vinorelbine(VNR),etoposide(EP),teniposide(TP).The main function of vegetable alkaloid is inhibition of mitosis,which can be applied to the tumor in eproductive system, blood system tumor.(4)Hormone:mainly includes tamoxifen, letrozole, etc., which was mainly used in chemotherapy of reproductive system tumor.The main mechanism of hormone is to treat the tumor growth which is regulated by hormone.Others:carboplatin (CP), cisplatin (cis-platinum), oxaliplatin, etc.Platinum chemotherapy drugs was used to treat a variety of tumors, including gastric cancer, liver cancer, ovarian cancer and breast cancer and it is common in the treatment of metastatic colorectal cancer.In addition, a new study of the evaluation of efficiency and security of bevacizumab combined chemotherapy based on 5-Fu,the scientists found that the patients who received 5-Fu/LV+bevacizumab 5 mg/kg has a longer disease-free surial which is significantly better than patients who were not.And the difference was statistical significant (P<0.05).In addition, in patients with stage IIB and III,other chemotherapy regimens include mFOLFOX6 and so on.Currently,5-Fu +folinic acid (5-Fu+(leucovorin, CF) is internationally recognized as a standard in the treatment of metastatic colorectal cancer,which is considered as the most efficient drug compatibility.And it has been recognised as a worldwide standard in the treatment of colorectal cancer chemotherapy.The administration of 5-Fu is special.Generally, a PVI therapy was used.PVI refers to the way of administration that in a longer period of time, by the administration with small doses, long time, continuous infusion to acheive a relatively continuous effect to avoid the poisoning of the drugs for tissues and organs.On the other hand, PVI therapy can keep a relatively stable blood concentration of drugs.In addition to, on the using of chemotherapy drugs, especially the use of 5-Fu, chronotherapy was often recommended.The chronotherapy refers to an administration way,according to the efficacy, tolerability and efficacy between day and night in treating colorectal cancer.This treatment can increase the susceptibility of the body to a certain drug and the dose of chemotherapy drugs, but minimize the side effects of drugs.The alternation of day and night to medicine, not only used in the chemotherapy of colorectal cancer, but also in breast cancer, stomach cancer, esophageal cancer.In colorectal cancer chemotherapy, no matter what kinds of chemotherapy regimens were used, we need to achieve the purpose of killing small lesions to reduce recurrence and improve survival rate.So it has been considered that in the patients with a high possibility of recurrence.chemotherapy was recommanded.The traditional idea is:for colon cancer, III period chemotherapy can prolong survival period,which is an indication of chemotherapy.For colorectal cancer, in stage I, chemotherapy is not recommanded,in stage II, ?,a combination of radiotherapy and chemotherapy after surgery was recommanded at the same time.Michael has reported that a chemotherapy was reasonable for all the colorectal cancer patients in stage II, ?.On the basis of 5-Fu, the duration of chemotherapy should generally combine the situation of patients, to acheive an improved efficiency.The prices, drug efficiency and the quality of life is closely linked.So,a great individual differences can be found on the time line of general chemotherapy.It has been generally believed that in the world,5-Fu based chemotherapy, the most effective treatments for colorectal cancer is one single year.At present,5-Fu+CF application for six months in treating metastatic colorectal cancer as a postoperative chemotherapy is one of the international standard.For the chemotherapy strategy of metastatic colorectal cancer, on the current,the 5-Fu+folinic acid was recommended internationally.,which has an great advantage that the price of 5-Fu is lower, so it has a higher compliance on chemotherapy.The effect of 5-Fu has an exciting antitumor efficiency in tumor, especially in adenocarcinoma, squamous carcinoma,which is widely used in breast cancer, ovarian cancer and chorionic carcinoma, cervical cancer, bladder cancer and so on.As a similar material to uracil,which is one of the component of ribonucleic acid,5-Fu has an and uracil is one of the one of the main components of RNA,5-Fu can functioning through blockage to the deoxidization nucleus, thereby inhibits the synthetase of intracellular thymidylic acid and thymidylic acid, thus inhibiting tumor cell DNA synthesis, moreover,it can also affect the synthesis of RNA through a similar mechanism and transcription.The 5-Fu based chemotherapy also has certain limitation, mainly because of the specificity of mechanism of 5-Fu is poorer on tumor killing, which also has certain damage to normal tissue.Patients with colorectal cancer who received a long-term treatment of 5-Fu, the susceptibility of tumor cells increases, i.e., when administrated with the same dose of the drug,the proliferation of tumor cells in the patients' body can't be inhibited.The main side effect of 5-FU is that it reduct the level of vitamin B12 obviously in the serum of patients.Therefore, it has been general suggested that in the use of 5-Fu,folic acid or its analogues should be administrated at the same time, in order to improve the megaloblastic anemia caused by Vitamin B12-deficiency.A combination of 5-Fu and folic acid was recommanded and the RBC and vitamin B12 levels should be follow-up.In addition to the usual chemotherapy drugs, there is a targeted therapy drugs, which has an important role in treating the metastatic colorectal cancer.Specific targeted therapy drugs is a kind of drugs that targets on the specific protein molecular on the tumor cell surface,which can effect on interaction with cell-cell or cell-drug in order to inhibit the malignant proliferation of tumor cells.As a targeting drug,the bevacizumab,as a kind of monoclonal antibodies,was used in metastatic cancer.Bevacizumab,also called Avastin (Bevacizumab, Avastin) is a restructuring of humanized monoclonal antibodies.Its main effect is confirmed by in vivo and in vitro testing system that it can combined with IgG1 antibody and vascular endothelial growth factor (VEGF) and further inhibits its biological activity.Avastin, in vitro and vivo, by combination with VEGF, it prevents the combination with surface receptors of endothelial cell Flt 1 and KDR.In angiogenesis model, avastin is confirmed that it can regulate the proliferation and angiogenesis by regulating the combination of VEGF and its specific receptor.On the basis of predecessors' research, we found that although the metastatic colorectal cancer chemotherapy and chemotherapy drugs emerge in endlessly, but, in Chinese mCRC patients, the clinical evidence of bevacizumab+irinotecan+5 fluorouracil+leucovorin,used in second-line is not sufficient.In this study,we investigated the use of bevacizumab+irinotecan+5-fluorouracil (5-FU) and leucovorin (FOLFIRI) in Chinese patients with metastatic colorectal cancer as the second-line chemotherapy.Based on this and the privious studies,we designed and applied the stratagy of this chemotherapy, which includes 5-Fu,bevacizumab,irinotecan,and leucovorin.Methods:patients with metastatic colorectal cancer, who had previously received basic chemotherapy of oxaliplatin without use of bevacizumab,were randomly assigned into two groups to receive bevacizumab plus FOLFIRI-B, or use FOLFIRI alone-B respectively.In patients treated with FOLFIRI-B, in every two weeks, the bevacizumab was used 10 mg/kg.The response rate and survival rate were observed.Results:From June 2010 to May 2014,65 patients were assigned to FOLFIRI-B group, 77 were assigned to the FOLFIRI simple treatment group.In FOLFIRI-B treatment group, the median progression-free surial (PFS) was 8.5 months (95% ci,5.8 to 10.5 months).In FOLFIRI alone treatment group,the median progression-free surial was 5.1 months (95% ci,2.7 to 9.8 months).In FOLFIRI-B group, the median overall survival (OSs) was 15.2 months (95% ci,11.8 to 19.4 months).In FOLFIRI alone group, the median overall survival was 11.3 months (95% ci,6.7 to 16.5 months).Conclusion:1. the second-line chemotherapy in patients with metastatic colorectal cancer in China, the efficiency of FOLFIRI-B is superior to FOLFIRI alone.2. FOLFIRI-B can be used as an auxiliary treatment method with a better security.It can be used in clinical application in patients with metastatic colorectal cancer. |
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