| Part One The efficacy of intraperitoneal chemotherapy with lobaplatin for colon cancer in abdominal metastasis implantation model in nude mice Object: To investigate the efficacy of lobaplatin administrating intraperitoneally for colon cancer in abdominal metastasis implantation model in nude mice, meanwhile to observe the prevention effect of intraperitoneal lobaplatin at the state of abdominal free cancer cells. Methods: 1. Preliminary experiment: 6 BALB/c-nu nude mice aging 5~6 weak weighing 18~22 g were chosed to establish the abdominal implantation model with Lo Vo human colon cancer cell line. Observation of tumor nodes was implemented on the 3rd, 5th and 7th day. On the 7th day, all mice were killed and exploratory laparotomy was perform to look for tumor nodes which would be sent to the pathology department; 2. Groups: Nude mice with the same condition as those in preliminary experiment were divided into four groups, namely, treatment group(group A), prevention group(group B), placebo group(group C) and the blank controller( group D). Each group included 6 nude mice; 3. Processing of each group: Mice in group A were treated with appropriate lobaplatin intraperitoneally at the 7th day from injecting cancer cells(Lo Vo, 5~10×106/ml, 0.2~0.3 ml); in group B, lobaplatin solution(diluted with 5% GS, 1:2000, 11 mg/kg) was infused just after the cancer cells injected into the abdomen; in group C, nude mice were performed with 5% GS with the equal volume as lobaplatin in group A, at the 7th day. In group D, nothing special was performed except for normal feeding during the whole procedure; 4. Items of observation: Weight change, ascites, survival time and tumor growth, after injection of tumor cells and lobaplatin, the observation time were two months. Results: 1. Preliminary experiment: All 6 nude mice in preliminary experiment were established the intraperitoneal transplantation model of colon cancer, as tumor nodes which were identified to be metastatic colon cancer pathologically at last were find in all mice. The success rate of establishing the model was 100%. 2. Tumors growing: Near the injection site, nodules appeared in group A, B and C in early time. One nodule was found in each mice in group A and C at the 5th to 7th day since the cells were injected. Nodules were discovered at the 10th(1/4)?11th(2/4)?12th(1/4) day in group B, the other two mice were not found nodules until opened the abdomen at the end of the trail. 3. Size of nodules: The average of the longest diameter of group A, B and C was 14.7 mm, 11.7mm, and 14 mm, respectively. Compared group C and group A or B the difference had no statistical significance(p>0.05), however there was significant statistical difference to compare group A and B(P<0.05). 4. Quantity of nodules(not including liver nodes): The average quantity of nodules in the abdomen of the mice in group A, B and C was 12.8, 10.5 and 27.5, respectively. There was significant statistical difference between each two groups(all, P<0.05), except between group A and B. 5. Sites of nodules: Tumor nodules were around the peritoneal cavity and the abdominal wall, the most common sites were the front and back right abdominal wall, the mesentery, the greater and the lesser omentum. Large nodules mainly in the right iliac fossa and on the lesser and greater omentum. Nodules in the hepar were pockety with different sizes. Liver nodes were found in group A, B and C, with the occurrence rate 50%(3/6), 16.7%(1/6), 83.3%(5/6), respectively. To compare group A and C, group B and C, the difference were both significant statistically(both, P<0.05). Group D did not have any nodes in the abdominal cavity. 6. Alteration of weight: Weight of the mice in group D improved, to the contrary weight of other mice tended to fall down. The average weight-alteration rates(final body weight/initial body weight) of the four groups were 0.76, 0.79, 0.67 and 1.14, respectively. The difference between group C and group A or B was statistical significant(P<0.05). 7. Death rate: Several nude mice died in the progress, except in group D. The total death rate of group A, B and C was 50%, 16.7%, 100% in turn. To compare group C with either A or B, the difference was significant statistically distinctly(P<0.05). Conclusion: 1. The intraperitoneal metastatic transplantation model of nude mice was successfully established by intraperitoneal injection with colon cancer Lo Vo line; 2. Intraperitoneal chemotherapy with lobaplatin can suppress the growing of abdominal free cancer cells, so that can delay the generation of peritoneal metastases;3. Intraperitoneal chemotherapy with lobaplatin can also decrease liver metastatic rate, and can reduce the death rate during a short time as prolonging the survival time and can improve the quality of life; 4. Intraperitoneal chemotherapy with lobaplatin may play an more significant role in preventing the generation of intraperitoneal reccurrence and metastasis of colon cancer after radical surgery. Part Two Security observation of intraoperative intraperitoneal chemotherapy with Lobaplatin for advanced colorectal cancers Objective: We aimed to observe the postoperative bowel function and complications of intraoperative intraperitoneal chemotherapy with Lobaplatin in patients with advanced colorectal tumor. Methods: Prospectively, between Oct. 2013 and Oct. 2014, 103 colorectal cancer patients underwent surgical operations in the gastrointestinal department of the first affiliated hospital of Southwest Medical University were included in this study. And all 103 patients were randomly divided into intraperitoneal chemotherapy group(55 cases) and control group(48 cases) according to the distribution of cases of random table. In therapy group, the patients were treated with intraperitoneal implantation of 40 mg Lobaplatin intraoperatively and followed by intravenous chemotherapy using FOLFOX regimen with Oxaliplatin, fluorouracil and leucovorin. And in control group, only FOLFOX regimen was fulfilled. Then the recovery time of bowel function, the occurrence of adverse reactions and complications, and the pre- and post-chemotherapy routine blood tests and hepatorenal functions were compared. Results: 1. The recovery time of bowel function in intraperitoneal chemotherapy group and control group were(72.1±11.8) hours and(68.7±13.4) hours, respectively, and there was no statistically significant difference(P>0.05). 2. Each group had 6 cases with incisional fat liquefaction(10.9% vs. 12.5%, P>0.05) and there were no serious infections. During intravenous chemotherapy, in intraperitoneal chemotherapy group and control group, the occurrences of nausea and vomit(42 cases, 76.4% vs. 40 cases, 83.3%), constipation(38 cases, 69.1% vs. 29 cases, 60.4%), and diarrhear(4 cases, 7.3% vs. 5 cases, 10.4%), were observed and there were no statistical significance(all P>0.05). It was noted that all these side effects vanished after chemotherapy or cured by symptomatic treatment. 3. There was no significant difference statistically between the two groups in indexes of white blood cell, blood platelet, alanine aminotransferase, aspartate transaminase, and creatinine(all P>0.05), neither after operation nor after chemotherapy. Conclusion: Intra-abdominal use of Lobaplatin as intraoperative chemotherapy for advanced colorectal cancer is safe and tolerable. |
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