He Wanbin appeared in the "Journal of gastrointestinal surgery in 2016 6 colorectal cancer incidence rate in China is third of the malignant
He Wanbin appeared in the "Journal of gastrointestinal surgery in 2016 6 colorectal cancer incidence rate in China is third of the malignant tumors, 20%~25% of patients with metastatic cancer that is at the same time, of which about 85% of patients with unresectable metastatic carcinoma [1,2]. The primary stage should not be removed from the metastatic stage IV colorectal cancer (colorectal with Irresectable metastasis, CRIM) whether the primary tumor should be removed, should be based on whether the primary lesions with symptoms of. Patients can be divided into obvious local symptoms (incomplete intestinal obstruction, intestinal perforation and hemorrhage wrapped with severe anemia), mild symptoms (a small amount of blood in the stool, defecation habits change but without significantly reduced exhaust defecation, etc.) and asymptomatic group 3. For patients with obvious symptoms, removal of the primary focus or early obstruction of the proximal end of the fistula can significantly prevent the occurrence of surgical complications. But for mild symptoms or asymptomatic patients should advance resection of the primary tumor was controversial, that observe the party believes that the core problem of such patients has been transformed into systemic tumor load, pre resection of the primary tumor by reducing the time delay of systemic therapy, neoadjuvant treatment period and will not fall into resectable lesions resection of the opportunity and risk of such patients with acute complications of surgery is not high [3,4]; advocate the operation party believes that the CRIM patients after the removal of the primary tumor can be avoided during the treatment and observation of intestinal obstruction, bleeding and perforation of acute symptoms, reduce the emergency operation due to the high mortality rate of [5,6]. This article mainly discusses the principle of primary treatment of patients with mild and asymptomatic CRIM.
Removal of the primary tumor may prevent or reduce surgical complications
The traditional opinion of CRIM for the removal of the primary tumor can effectively avoid complications such as bleeding and perforation, obstruction surgery, chemotherapy and follow-up observation, the SEER database also showed that 55%~77% treatment, CRIM patients received primary resection [7,8]. In the era of 5-FU chemotherapy alone, more than 20% of patients with CRIM need to undergo emergency surgery (). However, in the past 10 years, the combined chemotherapy regimen has a good control effect on primary symptoms (70%~80%) . With the wide application of intestinal stent and decompression device and the application of rectal cancer radiotherapy technology, the proportion of emergency surgery to relieve acute symptoms decreased significantly to 7%~10%. In view of this, the national comprehensive cancer network (NCCN) in 2009 began to recommend the treatment of asymptomatic CRIM patients with systemic therapy as the preferred treatment, the primary focus of the program to take close follow-up. Therefore, in recent years, the proportion of primary resection in patients with colorectal cancer showed a downward trend. SEER database showed that in 2009 CRIM patients with primary resection rate was only 50.7%.
Although the prevention of surgical complications of " " is not a sufficient reason to choose for primary tumor resection, taking into account the differences between advanced colon safety emergency surgery of rectal cancer, surgeons should still be on the pros and cons of emergency operation risk and preventive surgery were carefully weighing. Stillwell  of the meta-analysis included 14 studies including 2703 patients received prophylactic primary tumor resection, postoperative mortality within 30 d rate was 4.7% (127/2 694), the postoperative complication rate was 18% (413/2 296). A British study has also reported that 1046 cases of colorectal cancer with acute obstruction in patients with primary prevention of postoperative mortality as high as 15.7%. Domestic small equal  reports, 189 cases of patients with rectal cancer with palliative resection of primary tumor, 17 cases (9%) patients died, and the elderly, emergency medical complications and peritoneal metastasis are risk factors of perioperative death, the mortality rate was 5.7% for elective surgery, and emergency surgery is as high as 18.4%, similar to the overseas results. Thus, a single operation safety to consider, for the latter part of emergency operation risk is higher, and the good general condition of patients undergoing surgery should try to avoid complications, high mortality and high emergency operation brought.
Two, primary resection may bring survival benefit
A large number of retrospective studies and Meta analysis showed that the patients with CRIM after primary resection of primary tumor were more likely to have a significant survival benefit than those who received chemotherapy alone. The median survival time was 6.4 months or so [5,8,11]. Despite objections that: (1) review of this inevitably biased, good physical condition, tumor load is small and the younger and lower CEA levels were more surgery; (2) the different stages of the definition of unresectable metastatic carcinoma is not the same, some of the successful patients benefit impact to survive; (3) is not consistent in different periods of chemotherapy. However, overwhelming retrospective data suggest that removal of the primary site may be beneficial in patients with relatively early or better physical conditions in CRIM. The latest SEER database of 37793 patients with stage IV colorectal cancer data analysis, using propensity score matching method to remove the primary tumor resection group and chemotherapy group differences in CEA level, age and tumor site, still found primary tumor resection group patients had survival benefit, low HR value to 0.40 (95%CI:0.39~0.42, P< 0.001) . Although this significant difference could not be ruled out by the interference between the two groups of different chemotherapy regimens and the burden of different metastatic tumors, it was difficult to fully explain the difference between the two groups.
It is not clear why the primary resection of the primary tumor is associated with survival benefit when combined with systemic metastases. There is no prospective randomized controlled study to answer this question directly, and the two targeted RCT studies were slow and terminated due to illness. However, the results of a prospective randomized controlled trial of two patients with metastatic renal cancer showed that renal resection combined with immunotherapy may have a significant survival benefit [15,16]. Van der Wal  suggests that in primary colorectal lesions exist at the same time of hepatic metastasis around the micro expression of angiogenesis related molecules VEGFA and VEGFR-1 with metachronous liver metastasis was significantly enhanced, prompt primary tumor angiogenesis may play a role in maintaining liver metastases. Another study showed that primary tumor resection, preoperative elevated systemic inflammatory response index of neutrophil to lymphocyte ratio (NLR) decreased significantly in the postoperative prognosis is good, a significant reduction of NLR mainly occurred in the large primary tumor cases, prompt removal of the primary tumor may transfer bring the systemic immune status, inflammatory response and liver micro environment changes, which affects the development of  metastatic lesions.
In consideration of the primary benefit of survival of patients with CRIM, patients should be aware that CRIM is a highly mixed compound group, systemic tumor load, age, level of CEA, tumor differentiation, lesion and healthy body immune status significantly affect the prognosis of patients, prospective study design must give full consideration to the stratification the study of this group.
Three, the choice of surgical indications
Operation refers to the comprehensive consideration of syndrome from the following: (1) the relatively good prognosis in patients with CRIM : such as metastatic lesions were relatively limited (less than 25% of liver volume), less than 2, is expected to transfer organs in patients with postoperative chemotherapy is well tolerated, ECOG score of 2 or less; Li  pointed out that using the AAAP score (age > ALP >, 70 years old, ascites IU/L, platelet / lymphocyte; 160 > 162 and postoperative chemotherapy can not, if more than two poor prognostic) to determine prognosis; (2) colon or rectal cancer: phase of local excision of rectal cancer care primary, need to consider the existence of rectal cancer ampullary obstruction probability is relatively low, radiotherapy can achieve good local control and rectal resection and postoperative quality of life and low comprehensive factors. (3) if there is obstruction and bleeding risk factors: the lack of a reliable prediction of the obstruction factors, relatively speaking, lesion segment length, not by reducing exhaust defecation, colonoscopy, CT showed proximal bowel dilatation and thickening of the intestinal wall, constipation and other factors indicate high risk of intestinal obstruction. The severe anemia or ulcer patients should also be actively considered.
Four, the impact of surgery on patients
In clinical practice, many patients with colorectal cancer often hope for surgical treatment, and chemotherapy for " " past hope measures. Worster and other studies suggest that the early diagnosis of  in patients with early diagnosis is not willing to accept, followed by feeling helpless, and then seek positive treatment measures, the establishment of confidence in the treatment of disease. Therefore, in patients with resectable liver metastases from CRIM, appropriate timing of prophylactic resection of the primary tumor may in some way increase the patient's confidence in the treatment of the disease. However, there is no direct evidence to prove that the psychological impact of the operation can make patients survive.
Five, the timing of surgery
The core problem of CRIM patients has been transformed into a systemic tumor burden, surgery may delay the best time for systemic treatment, reduce the patients on chemotherapy tolerance, and for the assessment of recent bleeding and obstruction in low risk patients, could be considered systemic chemotherapy after surgical resection of primary tumor. But for the existence of obstruction of patients at risk, if not through colonoscopy or long segment lesions of patients, should give priority to the removal of the primary tumor, for patients with advanced rectal cancer can be considered at the same time, radiotherapy or sigmoid colostomy.
In conclusion, in view of modern surgery good surgical risk control and retrospective study showed that the removal of the primary tumor can obtain better survival benefit, with relatively good prognosis, good health and high risk patients with CRIM obstruction, are advised to consider the implementation of primary tumor resection in the right time, and the risk of obstruction the smaller patients should give priority to systemic chemotherapy after surgery in order to achieve the best therapeutic effect.
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