| BackgroundPrimary liver cancer(PLC) is a type of common malignant tumor in the digestive system, which is the fifth-leading cause of cancer death in the world. PLC is also a tumor with high incidence rate in China. Nowadays, about 55% of the worldwide new HCC cases take place in China and most of the histological type of PLC is hepatocellular carcinoma(HCC). The early clinical manifestations of HCC is not typical and usually results in neglect of the disease. When the typical symptoms and physical signs such as hepatalgia and abdominal mass starts to appear, the HCC patients are normally diagnosed to be at the intermediate or advanced stage, implying the high difficulty to cure. This situation in evitably leads to the high mortality of HCC patients. With the improvement of the medical standards in our country, the therapeutic methods such as surgical resection, liver transplantation, radiofrequency ablation, TACE and biotherapy and so on have been widely used in the treatment of HCC, which is helpful for improving the prognosis of HCC. However, HCC is not sensitive to radiation and chemotherapy treatment, whereas liver transplantation is hardly performed because of the lack of donors and its high cost. As a result, the first option in the treatment of HCC is radical resection. Although the success rate of radical resection has increased in the last two decades as the early diagnosis rate and the level of surgical treatment has been developing, the overall survival rate and the disease-free survival rate after operation have not been significantly improved. The related statistics shows that the five-year overall survival rate is only 15%-40%, and 60%-80% of patients recur in 2 years after operation. Postoperative recurrence especially early recurrence is the most serious problem that influences the prognosis of HCC after hepatectomy. Nowadays, how to improve the prognosis of HCC has become an important subject that we are faced with.In the recent years, the analysis of the factors influencing the prognosis of HCC has been a heated issue both domestically and internationally. Related studies have found that host factors such as sex/age/smoking history/drinking history/liver function/hepatitis etc., and neoplastic factors such as tumor size/ the number of tumor/tumor capsule/histopathological differentiation /vascular cancer embolus/metastasis etc. and treatment factors such as treatment methods/excision extension etc. were independent risk factors affecting the prognosis of HCC after radical resection of liver cancer. Nevertheless, these studies have paid more attention to the factors affecting the prognosis of HCC after comprehensive treatments but not the ones after radical resection. Meanwhile, these studies have mostly looked at the host factors and neoplastic factors rather than the operation factors and follow-up factors such as hyperglycaemia. Hyperglycaemia is a type of common metabolic complication after radical resection of liver cancer. Some research shows that genetic defect of NCOA5 induces HCC and hyperglycaemia. At the same time, hyperglycaemia, together with hyperinsulinism which is caused by hyperglycaemia, could promote the occurrence and development of HCC. The dispute about the relationship between postoperative hyperglycaemia and the recurrence of HCC continues.On the other hand, there is a research finding that hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy. To study the factors affecting the early recurrence after hepatocellular carcinoma radical excision, we used retrospective analysis of the clinical data of 145 patients who underwent curative hepatectomy for HCC at the Nan Fang Hospital from October 2009 to June 2013.We have focused on the relationship between hyperglycaemia and early recurrence after hepatocellular carcinoma (HCC) radical excision in the research, hoping to shed some light on the improvement of prognosis of HCC after radical excision.Data and methodThe clinical data of 145 patients who underwent curative hepatectomy for HCC at The Nan Fang Hospital from October 2009 to June 2013 was analyzed retrospectively, of which 135 cases were male,10 cases were female. Inclusion criteria:(1)Patients who were diagnosis with HCC before surgery without transmigration and the number of tumor nodules was less than 3. (2)Patients’ physical condition satisfied the operative indication of radical resection of liver cancer, and HCC was confirmed by the postoperative pathological examination. (3) No cancer embolus was finding in the common hepatic duct and its first grade branch nor portal vein and its first grade branch nor hepatic vein trunk nor inferior vena cava. (4)Patients had not received other anti-tumor treatments before or during operations, and no histories of other tumors were recorded. (5)No postoperative complications occurred and the clinical data was integrated. Exclusion criteria:(1)Patients who were diagnosed with endocrine disease that may affect FBG(diabetes excepted). (2)Tumor rupture or invasion of adjacent organs was found during the operation. (3) Other histological type was confirmed by the postoperative pathological examination. (4)Patients passed away in perioperative period, recurred within 2 months after the operation or were not followed up after 24 months after the operations. (5) Follow-up information was not complete.Clinical data consists of the following elements:(1) general information (gender, age, FBG, HbsAg, anti-HCV, underlying hepatopathy, preoperative AFP, albumin(Alb), total bilirubin(Tbil), prothrombin time(PT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), ascites, hepatic encephalopathy, Child-Pugh stage, Barcelona Clinic Liver Cancer (BCLC) stage, history of alcohol drinking and smoking); (2) surgical data (surgical date, surgical method, operation time, number of blood transfusion, volume of intraoperative blood loss), pathological data (histological type, histopathological differentiation, number of tumor nodules, diameter of maximal tumor, liver cirrhosis); (3) follow-up data(postoperative AFP, imaging findings, recurrence time, preventive chemotherapy).Next, the diagnostic criterion of liver cancer is displayed:Based on the following conditions, the diagnosis of liver cancer could be confirmed if both (1) and (2)a are satisfied, or (1), (2)b and (3) are satisfied simultaneously. The conditions:(1)Patients with liver cirrhosis or are infected with hepatitis B or hepatitis C;(2)Imaging results have typical radiologic characteristic of HCC:(a) While the diameter of liver lesion is greater than 2cm,the diagnosis of HCC could be confirmed if one of the CT or MRI findings was positive.(b) While the diameter of liver lesion is less than 2cm,the diagnosis of HCC could be confirmed if both the CT and MRI findings were positive.(3)AFP≧400ug/L lasts for 1 month or AFP≧200ug/L lasts for 2 months, and other reasons for an elevated AFP such as pregnancy, genital embryonic tumors, active liver disease or secondary hepatic carcinoma could be excluded.The diagnosis of recurrence of liver cancer was subject to dynamic contrast enhanced scanning such as CT,MRI,PET-CT and hepatic arteriography. Results found through ultrasono graphy or having elevated AFP could not lead to the diagnosis of recurrence of liver cancer.The operative indication and criterion of radical resection of liver cancer is based on<The norm of diagnosis and treatment for primary liver cancer(2011)>.The method of follow-up visits:Patients had reexaminations once in a month in the first 6 months after operations, and once every 3 months after 6 months. Follow-up visits ended once the first recurrence appears. Follow-up of outpatient examination was conducted up to July 1,2015.The monitoring method of FBG and the definition of postoperative hyperglycemia:Measuring FBG in the first, third, fifth and the seventh postoperative day. During the follow-up period, FBF was measured according to the follow-up method. Next, the FBG measured during hospitalization were added together and the mean was taken as the representative of the FBG of hospitalization. Summing it up with the FBG from the follow-up period, and the mean was subsequently calculated as the patient’s averaged blood glucose. So postoperative hyperglycemia is defined if a patient’s averaged blood glucose≧ 6.1mmol/L.The calculation method of volume of intraoperative blood transfusion:According to the anesthesia records and the operation records, transfusing 1 unit of red cell or 100 mL of blood plasmawas counted as 100mL volume of intraoperative blood transfusion. Summing up the volume of red cell with the volume of blood plasma and the sum was calculated as the patient’s volume of intraoperative blood transfusion.Use of statistical method:The SPSS 19.0 software was used for statistical processing. Measurement data with normal distribution were presented as x±s and analyzed by the t test. Measurement data with skewed distribution were presented as M (range) and analyzed by the nonparametric test. Count data were analyzed using the chi-square test. With the first recurrence as the end point, the tumor-free survival rate was drawn using the Kaplan Meier method, and the comparison was analyzed by the log rank test. The risk factors affecting recurrence were analyzed using the Kaplan Meier method for proportional hazards assumption test firstly, and then eligible factors were done using Log rank test in the univariate analysis. The multivariate analysis was conducted using the COX model. According to a=0.05 level of test, P< 0.05 implies that the difference is statistically significant.Results145 cases were included, of which 135 cases were male (93.1%)and 10 cases were female (6.9%). The average age was 51. Patients were followed up for between 2 to 67 months, and the median follow-up time is longer than 24months.Overall, the recurrence rate in the 1st and 2nd postoperative year is 28.3%(41/145) and 45.5%(66/ 145) respectively. Comparatively, the figures are 21.6%(24/111) and 36.9%(41/111) in the normal group, and 50.0%(17/34) and 73.5%(25/34) in the hyperglycemic group, showing a significant difference between the 2 groups (x2= 10.335,14.053, PO.05). Furthermore, the univariate analysis displays that FBG, postoperative AFP, volume of intraoperative blood transfusion and Child Pugh stage are risk factors affecting tumor-free survival rate after radical resection of liver cancer. The median disease-free survival time in the normal group and hyperglycemic group are>24months and 10 months respectively. The median disease-free survival time for normal level and postoperative level of AFP>8.1ng/mL are>24 months and 8 months respectively. The median disease-free survival time for group with<200mL volume of intraoperative blood transfusion and its comparative group are>24months and 10 months respectively. And the time for the Child-Pugh A grade group and Child-Pugh B grade group are>24months and 16 months respectively. The results proves that the difference between the 2 groups is statistically significant (x2=17.591,12.820,10.690, 6.492, P<0.05). The results of multivariate analysis shows that level of FBG≧6.1 mmol/L, postoperative level of AFP>8.1ng/mL and volume of intraoperative blood transfusion>200mL are independent risk factors affecting tumor-free survival rate after radical resection of liver cancer (RR=2.542,2.724,2.028,95% confidence interval:1.529-4.225,1.635-4.538,1.183-3.479,P<0.05).ConclusionIn conclusion, FBG, postoperative AFP and the volume of intraoperative blood transfusion are independent risk factors affecting prognosis after radical resection of liver cancer.Generally speaking, the good performance during surgery, the reduction of intraoperative hemorrhage in the surgery, the avoid chance of perioperation blood infusion, the close monitoring and controlling of blood glucose after operation could be helpful in improving the prognosis of patients with liver cancer. Monitoring AFP after operation is quite important in predicting the prognosis of patients with liver cancer. |
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