Abstract
OBJECTIVE The present study was designed to develop the "Three - Grade Criteria" for radical resection of primary liver cancer (PLC) and to evaluate its clinical significance.
METHODS Criteria for radical resection of PLC were summed up to 3 grades based on criterion development. Grade I: complete removal of all gross tumors with no residual tumor at the excision margin. Grade II: on the basis of Grade I, additional 4 requirements were added: (1) the tumor was not more than two in number; (2) no tumor thrombi in the main trunks or the primary branches of the portal vein, the common hepatic duct or its primary branches, the hepatic veins or the inferior vena cava; (3)no hilar lymph nodes metastases; (4)no extrahepatic metastases. Grade III : in addition to the above criteria, negative postoperative follow-up result including AFP dropping to a normal level (with positive AFP before surgery) within 2 months after operation, and no residual tumor upon diagnostic imaging.The clinical data from 354 patients with PLC who underwent hepatectomy were reviewed retrospectively. Based on the "Three-Grade Criteria” these patients were divided into 6 groups: Grade I radical group, Grade I palliative group, Grade II radical group, Grade II palliative group, Grade III radical group, Grade III palliative group. The survival rate of each group was calculated by the life-table method and the rates compared among the groups.
RESULTS The survival rate of patients receiving radical treatment was better than those receiving palliative treatment (P<0.01). Survival improved as more criteria were applied. The 5-year survival rate of the patients in Grade I, II and III who underwent radical resection was 43.2%, 51.2% and 64.4%, respectively (P<0.01).
CONCLUSION The "Three-Grade Criteria" may be applied for judging the curability of resection therapy for PLC. The stricter the criterion used, the better the survival would be. Adopting high-grade criteria to select cases and guide operations and strengthening postoperative follow-up would improve the results of hepatectomy for PLC.
keywords
At the present time the criteria of radical resection for primary liver cancer (PLC) have not been unanimous. The concept of radical resection for PLC was established simply before the 1980’s, as a complete resection of the gross tumor by most scholars.[1] Over time, the concept of an ideal radical resection for PLC developed further. In the 1990’s, many scholars had recognized the influence of tumor biological characteristics for the effectiveness of PLC resection and the importance of postoperative follow-up for appraising a radical resection.[2-4] All kinds of criteria for radical resections of PLC could be summed up to 3 types: the criterion making the surgical factors as a major concern, the criterion combining the tumor factors, and the criterion combining the results of postoperative followup.[2-7] It was easy to find that there were not only differences but also a connection among the 3 criteria for radical resection mentioned above. The second and third criterion not only preserved all the content of the former but also added some new features to be applied gradually. If the 3 kinds of criteria for radical resection of PLC were named as "Three-Grade Criteria" this would define the development of the lesions and reflect the internal connection among the criteria more, and be helpful for managing and deciding on the criteria for radical resection. Accordingly, we attempted to introduce a definition for the "Three-Grade Criteria" (that is Grade I, Grade II and Grade III) in this report.
MATERIALS AND METHODS
Case selection
From January 1995 to December 1999, 373 patients with PLC underwent hepatectomy in our hospital. In order to determine the postoperative survival accurately for these patients, 12 cases who received treatment before January 1995 and 7 cases who died during hospitalization were excluded from our study, so only 354 out of the 373 patients were used for analysis. These 354 patients were consistently followed-up to December 2001, and 346 of them provided complete follow-up data for a rate of 97.7%. There were 293 males and 61 females, with a mean age of 49.3 years. α-Feto- protein (AFP) was positive in 65.8% of the patients. The pathological diagnosis for these patients were all PLC, of which 97.8% were hepatocellular carcinoma. Small hepatic cancer (diameter less than 5 cm) was found in 49.4% of the patients. The number of tumors was less than two in 96.3% of the patients and 85.6% patients had complication of hepatic cirrhosis. Intraop- eratively we found 36 cases with tumor thrombi in the inferior vena cava and main trunks of the hepatic vein, and 7 cases were complicated with extrahepatic metastases. The distribution of tumors revealed 27.7% in the left lobe, 57.6% in the right lobe, 4.85% in the middle lobe, 8.5% in both left and right lobes and 1.4% in the caudate lobe.
The "Three-Grade Criteria" for evaluating radical resection
Based on the completeness of the radical resection criteria, the cases were divided into 3 grades, that is Grade I, Grade II and Grade III. Grade I: complete resection of all gross tumor mass with no residual tumors at the incision margin. Grade II: on the basis of Grade I, 4 requirements were added: (1) the tumor was not more than two in number; (2) no tumor thrombi in the main trunks or the primary branches of the portal vein, the common hepatic duct and its primary branches, the hepatic vein or the inferior vena cava; (3) no hilar lymph nodes metastases; (4)no extrahepatic metastases. Grade III: in addition to the grade II criteria, negative postoperative follow-up result including AFP dropping to a normal level (with positive AFP before surgery) within 2 months after operation and no residual tumor upon diagnostic imaging. The above criteria were formed on the basis of blending the opinions of the authors of this report and other coworkers in this field (Table 1).[3]
Content of the "Three-Grade Criteria" of radical resection for PLC.
Grouping
The 354 patients were divided into 6 groups based on different criteria: Grade I radical group (346 cases), Grade I palliative group (8 cases); Grade II radical group (288 cases), Grade II palliative group (58 cases); Grade III radical group (219 cases), Grade III palliative group (69 cases). In the same Grade (Grade II or Grade HI), the radical group and the palliative group were separated from the relatively low criteria radical group (Grade I radical group or Grade II radical group) (Fig. 1).
The 345 cases devided into groups based on the "Three-Grade Criteria" of radical resection for liver cancer
Statistical analysis
The survival rate was taken as the evaluation basis for the comparison between different groups. The survival rate was calculated by the life- table method and the comparison among groups was expressed by the Log rank test. The non-disease survival rate was performed only in the confinement of the Crade III radical group. All data were managed by Access 2000 and analyzed statistically by SPSS 10.0.
RESULTS
The postoperative overall 5-year survival rate of 354 PLC patients who underwent hepatectomy was 42.1%.
The survival rates of the patients in the radical groups were higher than those in the palliative groups within the same Grade. The 5-year survival rates of the radical vs. the palliative group in Grade I, II and III were 43.2% vs. 0%; 51.2% vs. 3.5%; and 64.4% vs. 11.1 %, respectively (P<0.01).
With increasing the Grade of the radical resection group, the survival rate also increased correlatively in increments. The 5-year survival rates calculated from I, II, III grade criteria for radical resection groups were 43.2%, 51.2% and 64.4% respectively (P<0.01, Table 2). The 1,3,5-year non-tumor survival rates were 89.8%, 60.0% and 44.5% respectively for 219 cases of Grade III criteria radical resection group.
Comparison of the survival rate among the groups according to the "Three-Grade Criteria" of radical resection for PLC in 354 cases.
DISCUSSION
Some considerations for determining the specific items of the "Three-Grade Criteria" for radical resection of hepatic cancer
Different opinions concerning the determination of the specific criteria for radical resection of hepatic cancer have long been under discussion. At the present time many scholars suggest that the distance between the surgical margin and the tumor should not be taken as a criterion for radical resection.[8,9] A great number of hepatic cancers adjoined to the major ducts/or vessels of the liver, less than 1 cm in distance between them and even adhering to each other. But these hepatic cancers now can be completely resected and will have better therapeutic effectiveness due to skillful im provement in the technique. Our previous study demonstrated that there was no significant effective difference between the resection of a single-tumor and that of a two-tumor, simultaneously, but it was worse with 3 or more tumors (2-year survival rate was only 33.8%, P<0.01).[3] Consequently, we made the existing number of tumors as one of the features for radical resection criteria. Tumor thrombi in the portal vein were also considered to be one of the main factors influencing the recurrence and prognosis.[8,9] Our previous studies also presented that the operative effectiveness for patients complicated with tumor thrombi in the major ducts and vessels was poor; the 1-year survival rate of patients with portal venous tumor thrombi was only 44.9%, and almost none of them survived for 3 years after hepatectomy. Okada et al.[10] pointed out that thrombi in an extraportal vein always indicated a tendency for early metastasis influencing the radical therapy. Besides, some other authors revealed that the 1-year survival rate of patients complicated with extraportal venous thrombi (in the hepatic bile duct, the common bile duct, the hepatic vein and the inferior vena cava) was only 18.6%.[3] Thus the presence/absence of thrombi in the major ducts or vessels were also included in the criteria of radical resection for hepatic cancer.
Theoretically, evaluating the effectiveness of radical resection for hepatic cancer statistically should be based on the non-tumor survival rate. The 1-, 3-, 5-year non-tumor survival rates of 219 patients in the Grade III radical group were 89.8%, 60.0% and 44.5% respectively. Practically, there would be more difficulties in registration and follow-up adopting the method based on non-tumor survival. Therefore, it is too soon to advocate this method.
The clinical significance in determination of the "Three-Grade Criteria" for radical resection of hepatic cancer and the authors personal opinion
Although the therapeutic procedures were all involved in the radical resection for PLC, the different criteria adopted would result in different degrees of efficacy. Hence, the establishment of the "Three-Grade Criteria" for radical resection presents a great practical significance for clinical doctors with respect to mastering indications for operation, the selection of the cases and the comparison of the effectiveness.
Even if the hepatic cancer is a solitary one, the determination and application of the "Three-Grade Criteria" for radical resection of hepatic cancer has had many difficulties because of its specific biological characteristics and the requirements for a more complex surgical technique. Under the circumstances exˆ>perts in the field fail to agree on using one kind criterion, but it is important to establish one criterion quickly in order to improve the surgical curative level of hepatic cancer. Therefore the suggestion of the "Three- Grade Criteria" possesses a definite practical significance. We tend to apply the criteria in 2 steps at present: first, in a hospital with sufficient conditions, the higher and stricter Grade II or III criteria should be adopted; second, in a hospital with insufficient conditions, the simple Grade I criterion could be adopted for surgical treatment of hepatic cancer, and Grade III criterion could also be consistently adopted after improvement of the conditions. The basis of our adoption for the two-step policy relies on the following two considerations: on the one hand, the "Three-Grade Criteria" is not yet perfect, and its generality will be further determined in the future by clinical practice; on the other hand, it is not practicable to employ the criteria widely at the present time.
- Received November 20, 2004.
- Accepted August 29, 2005.
- Copyright © 2005 by Tianjin Medical University Cancer Institute & Hospital and Springer
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