| BackgroundColorectal cancer is the third most common malignancy worldwide, nearly 1.4 million new cases every year, for about 694,000 deaths. Because the Chinese people on the low awareness of colorectal cancer and early colorectal cancer may be asymptomatic or because of the lack of specific symptoms, so it is difficult to pay attention. When patients with lower abdominal pain or accompanied by bleeding, melena, obstruction and other complications and can be palpable abdominal unusual package piece, inguinal lymph node enlargement, rectum pouch tumor, umbilical mass even merge ascites, jaundice, ovarian enlargement, difficulty in breathing etc. tumor metastasis symptoms and treatment, the majority has entered the development period. Surgical resection of tumor is the treatment of colorectal cancer the main and effective method, but simple surgical excision to improve the prognosis of patients with more limited, combined with other therapies, including radiotherapy, chemotherapy, molecular biology therapy and traditional Chinese medicine treatment. Wan-qing Chen analysis of national central cancer registries and high quality data, 2015 new cases of colorectal cancer in China is expected to 376.3×103, ranked third, second only to lung cancer and stomach cancer,191×103 death cases. About 50% new cases every year in the advanced stage, postoperative 5 years survival rate hovers around 40%～30%. Among them, colorectal cancer and peritoneal metastasis of colorectal cancer has become the most common cause of death and lead to recurrence after radical resection, median survival was only 7 months, has been a serious threat to people’s life and health. Intraperitoneal free cancer cells (FCC) and microscopic cancer (MC) are the main risk factors of peritoneal metastasis. Therefore, how to effectively remove the free cancer cells in peritoneal cavity and small foci become key to the prevention of peritoneal recurrence and metastasis of postoperative colorectal cancer. Because the radiotherapy is easy to cause radioactive enteritis, resulting in adhesive intestinal obstruction, clinically used only for low rectal cancer. Due to the existence of " peritoneal-plasma barrier" and systemic venous chemotherapy makes into the abdominal cavity chemotherapy drug concentration is not sufficient to completely kill the remaining free cancer cells and microscopic cancer, curative effect is poor and because of the side effects of chemotherapy with the course of increasing gradually increase, resulting in many patients cannot tolerate and unable to complete a given course and reduce efficacy. After 30 years of development, hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to effectively improve the postoperative patients with colorectal cancer and 5 year survival rate. The principle based on high temperature on tumor cells directly killing effect, local chemotherapy and thermotherapy and chemotherapy synergistic effect and large capacity of chemotherapy liquid for abdominal mechanical lavage role, effectively remove node rectal carcinoma postoperative intra-abdominal residual free cancer cells and microscopic cancer that has become the prevention and cure of the node after resection of rectal cancer intraperitoneal recurrence and metastasis of a very important for the treatment.ObjectiveIntraperitoneal free cancer cells and the existence of microscopic cancer is the main risk of colorectal cancer after radical resection of peritoneal metastasis factors. The study found that falling into the number and serous peritoneal free cancer cells within the invasion range (that is closely related to the tumor T stage) and the biological behavior of tumor cells is proportional to the. Therefore, how to prevent the recurrence and metastasis of abdominal cavity in order to improve the prognosis of patients has important clinical significance. Hyperthermic intraperitoneal chemotherapy has been confirmed by clinical research can effectively prevent and reduce peritoneal free cancer cells of patients with colorectal cancer after planting, improve survival rate and life quality. However, most clinically studies for patients are advanced colorectal cancer patients after operation, including T2, T3, and T4 patients, the proportions of the 3 patients in the study, confusing HIPEC for treatment of patients with advanced colorectal cancer, especially when the T4 patients accounted for less, its efficacy tend to be magnified. In view of the T4 stage colorectal cancer is in the presence of intraperitoneal free cancer cells the main risk factors, this study aims to investigate T4 stage after operation in patients with colorectal cancer of early HIPEC clinical efficacy, ruling out the effects of different T stages on curative effect, for this treatment can have to provide the clinical basis for improving the prognosis of patients with advanced colorectal cancer.Materials and Methods1.the object of study1.1 material. A retrospective analysis of our hospital department of general surgery from January 2011 to June 2013 were T4 stage colorectal cancer patients. T4 stage total of 96 patients were enrolled, in radical surgery were divided into two groups, each group of 48 cases. (1) The HIPEC group:31 cases of male,17 female patients, median age 51 years; pathological types:37 cases of high and moderately differentiated adenocarcinoma; low differentiated adenocarcinoma in 6 cases; 4 cases of mucinous adenocarcinoma, signet ring cell carcinoma in 1 case; operation mode: colon regional resection in 37 cases, and Miles operation was performed in 1 cases, Dixon operation in 10 cases. (2) The control group:33 cases were male,15 female patients, average age (51+10.7 years); pathological types:high, a moderately differentiated adenocarcinoma in 29 cases;low, undifferentiated adenocarcinoma in 11 cases; mucinous adenocarcinoma, mucinous cell carcinoma in 5 cases,3 cases of signet ring cell carcinoma; surgery:colon regional resection in 37 cases, and Miles operation was performed in 3 cases, Dixon operation in 8 cases. Two groups of gender, age, pathological type, surgical methods were comparable (P> 0.05). Two groups of patients signed informed consent.1.2 The inclusion and exclusion criteria. Inclusion criteria:(1) underwent preoperative endoscopic and pathologic study confirmed and abdominal CT examination and preoperative evaluation of parallel to exclude existing liver, lung and other distant metastasis; (2) of bone marrow function is normal, without contraindication to chemotherapy; (3) without preoperative radiotherapy and chemotherapy history; (4) after operation according to paraffin pathology, tumor diagnosis has violated intestinal serosa layer (T4); (5), Karnofsky score> 60 points, the expected survival time more than three months. Exclusion criteria:(1) preoperative assessment of tumor related examination has been unable to complete resection; (2) did not reach the standard radical operation. 2. Therapeutic method2.1 Surgical operation. Two groups of patients were operated by the same team of doctors performed radical resection of colorectal cancer. The HIPEC group before the close of the abdominal cavity of patients on the left and right of the both sides of the pelvic and abdominal placed one root tube perfusion, perfusion on both sides of the inlet duct is located in rib arch below 3cm and midclavicular line at the intersection of, on both sides of the perfusion outlet duct in the umbilical cord and the anterior superior iliac spine line and 1/3 and suture fixation in abdominal skin, four perfusion tube are connected drainage bottle, to be post perfusion chemotherapy with. Patients in the control group in the abdominal cavity placed one rubber drainage tube connected with a drainage bottle.2.2 Chemotherapy method. (1) The HIPEC group:the use of BR-TRG-I hyperthermic perfusion machine and BR-TRG-I type disposable medical special circulation pipeline (produced by Guangzhou Baorui Medical Technology Co., Ltd.), HIPEC were implemented after 5 or 6 days after operation. Perfusion method: perfusion chemotherapy in non anesthetized, before reperfusion to remove perfusion drainage tube of fibrous tissue, blood coagulation and necrosis of tissue loss. Half an hour before the start of perfusion to give prophylactic analgesia, sedation. HIPEC equipment used in the perfusion fluid (cisplatin of 100mg plus fluorouracil of 1.0g completely dissolved in 3000ml saline solution) is heated to 43℃, was injected into the peritoneal cavity by flow velocity of 200-400ml/min, through the temperature control system of the computer the temperature stability in the abdominal cavity in (43±0.5)℃ for 60 minutes. During the perfusion of patients with ECG monitoring, to low flow oxygen (2L/min). The perfusion flow control at any time according to the patient, the intraperitoneal chemotherapy perfusion fluid volume control in 2000～2500ml. At the end of the reperfusion, indwelling about 1000 1200ml perfusion fluid in the abdominal cavity, perfusion tube drainage bottle, the intraperitoneal residual perfusion fluid flowing slowly. One times a day, a total of 3 times. All patients started mfolfox6 chemotherapy after operation in a month. Adverse reaction of chemotherapy during chemotherapy and post chemotherapy period are monitoring and recording. Check routine blood 2 times per week during chemotherapy, each cycle of chemotherapy before review of liver and kidney function, electrocardiogram, chest X-ray, etc.Colonoscopy and periodic review of abdominal ultrasound or CT evaluation of curative effect. (2) control group:postoperative January start intravenous chemotherapy, and chemotherapy treatment scheme were the same as group HIPEC.3. Observation index3.1 The adverse reactions and complications. Such as bone marrow suppression, gastrointestinal toxicity, wound infection, anastomotic fistula and obstruction. The adverse reaction according to the World Health Organization (WHO) standard chemotherapy drug toxicity is divided into 0～IV.3.2 The recurrence rate and survival rate. After first to 2 years were followed every 3 months for one times. The follow-up period periodic review colonoscopy, abdominal ultrasound, CT, liver and kidney function and tumor marker material, statistics of patients with postoperative 1 and 2 years recurrence rate and survival rate.3.3 Quality of life assessmen. Application of Karnofsky (KPS) standard respectively before treatment and at the end of the on the quality of life of the patients were assessed divided into increased, stability, reducing the level 3, namely after the end of treatment, compared with before scoring 10 points to increase increased 10 points were reduced to reduce, increase or decrease less to 10 points were stable.4. Statistical treatmentApplication of SPSS 20.0 software was used for statistical analysis, count data using chi square test, univariate survival analysis using the Kaplan Meier’s method, P < 0.05 visual for the difference has statistical significance.Results1. two groups of adverse reactions and complications:two groups of patients had no surgery related death, there were no wound infection, anastomotic fistula and adhesive intestinal obstruction and other complications. Two groups of patients with bone marrow suppression, nausea, vomiting, liver function damage incidence of adverse reactions were not statistically significant (P> 0.05); The HIPEC group abdominal pain and fever and compared with the control group, the difference is statistically significant (P<0.05).2. two groups of recurrence rate and survival rate:The HIPEC group after HIPEC and systemic chemotherapy were successfully completed, follow-up rate of 100%; The 1-year and 2-year recurrence rate of HIPEC group were lower than those of the control group significantly (2.1% vs.20.8%; 6.3%vs.31.3%, P< 0.05); There were no differences in 1-year survival rate between the two groups (P>0.05), but the 2-year survival rate was higher than that of the control group significantly (81.3% vs.58.3%,P<0.05).3. Treatment of the two groups before and after the comparison of the quality of life (KPS score). The quality of life in HIPEC group were higher than those of the control group significantly (75.0%vs.25.0%, P< 0.05).Conclusion1. Hyperthermic intraperitoneal chemotherapy can effectively control the peritoneal recurrence and metastasis of stage T4 colorectal cancer patients after surgery, improve patient survival and quality of life.2. Hyperthermic intraperitoneal chemotherapy did not significantly increase the side effects and complications of patients after operation, which is safe and feasible.3.Hyperthermic intraperitoneal chemotherapy has no special requirements on the working environment, is T4 stage colorectal cancer patients especially suspicious of abdominal FCC adjuvant therapy in patients with positive ideal, worthy of further study. |
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