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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

Aim : To compare the clinico-pathological features of hepatitis B virus-related hepatocellular carcinoma in young and old patients.

Methods : The clinico-pathological characteristics of hepatitis B virus-related hepatocellular carcinoma were compared in 1863 consecutive patients (121 patients, ≤40 years; 1742 patients, > 40 years) seen at a single institution over the last 13 years.

Results : Young patients presented more often with pain (P < 0.0001), hepatomegaly (P = 0.01) and ruptured hepatocellular carcinoma (P = 0.02), whereas old patients presented with ankle oedema (P = 0.001), ascites (P = 0.002) and by routine screening (P = 0.035). Liver function, Child–Pugh grading and indocyanine green test were better preserved in young patients. They also had a higher α-foetoprotein concentration (P = 0.001), larger tumour size (P = 0.001) and more frequent metastasis (P = 0.008), but a similar surgical resection rate (33.6% vs. 28%), to old patients. There was no difference between the two groups in the overall post-resection survival rate, but there was a shorter survival in young patients with unresectable disease (3.6 months vs. 4.6 months, P = 0.004).

Conclusion : Young patients with hepatocellular carcinoma often show a later presentation, but a higher resectability rate and similar survival rates, than old patients. The screening programme should include young hepatitis B virus carriers, even in the absence of cirrhosis.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

Hepatocellular carcinoma is the fourth most common cancer in the world.1 Despite a lower incidence of hepatocellular carcinoma in Western society, a clear increase has been documented in the USA,2 Japan and Western Europe.3 Hepatocellular carcinoma is the second most common cancer in males and the fourth most common cancer in females in Hong Kong.4

Chronic hepatitis B and C infections are recognized as the major risk factors for hepatocellular carcinoma.5–12 In Hong Kong, the prevalence of hepatitis B virus carriers has been estimated to be 10%. The incidence of hepatocellular carcinoma in individuals with chronic hepatitis B infection is as high as 0.46% per year.13–16 Cirrhosis, irrespective of aetiology, is another risk factor for hepatocellular carcinoma. The annual risk of developing hepatocellular carcinoma in cirrhotic patients is between 1% and 6%.17–23 About 80% of patients with hepatocellular carcinoma have cirrhosis.24 Other risk factors, including chemical, nutritional, hormonal and genetic factors, have also been implicated as causes of hepato-carcinogenesis.25

Although the issue of cost-effectiveness for screening in hepatocellular carcinoma has yet to be proven, it is usually recommended that mass screening should be performed in hepatitis B endemic areas, such as South-East Asia. Beasley et al. have reported that the risk of hepatocellular carcinoma in hepatitis B virus carriers is negligible before the age of 30 years.5 Hence, the target population for screening is usually limited to the elderly, and those who have concomitant cirrhosis or a family history of hepatocellular carcinoma. The younger age group is therefore neglected in the screening programme.

Recent reports from Japan and Hong Kong have indicated that younger patients with hepatocellular carcinoma are more likely to be hepatitis B virus carriers, have higher serum concentration of α-foetoprotein and have better liver function when compared with older patients.26–28 It has been postulated that there may be different mechanisms of hepato-carcinogenesis according to the age distribution of patients.26 However, we postulated that the difference could be due to the different presentation in young and old patients with hepatitis B virus-associated hepatocellular carcinoma. In this study, we examined the characteristics of hepatocellular carcinoma in young adults and in an older age group in a single institution over the last 13 years, with emphasis on clinical presentation, liver function and prognosis in the two groups. Our findings support the hypothesis that differences in the clinical features in young and old patients with hepatocellular carcinoma may be due to their different presentation. This may have an impact on the current screening strategy.

Patients and methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

From January 1, 1989 to December 31, 2001, 1863 consecutive patients with hepatitis B viral infection and hepatocellular carcinoma were managed at the Centre for Liver Disease, Department of Surgery, Queen Mary Hospital, Hong Kong. All clinico-pathological data were collected prospectively, encoded according to a standardized coding system and entered into the Tumor Registry by the same researcher during the studied period in order to reduce inter-observer error. We arbitrarily defined young patients as those aged less than or equal to 40 years at diagnosis. The cut-off of 40 years was taken because this was the cut-off used for young hepatocellular carcinoma in another study in the Chinese population.29 Of these 1863 patients, 121 (6.5%) were 40 years of age or younger. We obtained a 99% follow-up rate for our patients, and the survival data and statistics were based on 119 (98%) young and 1725 (99%) old patients. We lost the remaining 19 patients to follow-up.

The family history of hepatocellular carcinoma, gender, symptoms, histological features, pre-operative studies, clinical and pathological staging, type of surgical procedure, resection rate, surgical morbidity and mortality, post-operative management and survival were analysed in all patients.

Diagnosis and staging of hepatocellular carcinoma

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

Cirrhosis was classified according to the Child–Pugh criteria. In 998 (53.6%) patients, the diagnosis of hepatocellular carcinoma was based on pathological examination of samples obtained by surgical resection, tru-cut biopsy or fine-needle aspiration cytology. For the remaining 865 patients, the diagnosis was based on the occurrence of the following criteria: (i) proven chronic liver disease caused by hepatitis B virus or hepatitis C virus; (ii) serum concentration of α-foetoprotein higher than 20 ng/mL (434/865; 50.2%); and (iii) the presence of a space-occupying hepatic lesion with characteristic features of hepatoma on imaging studies, such as computed tomography scan (368/865; 42.5%), angiography (324/865; 37.5%) or magnetic resonance imaging scan (32/865; 3.7%).

The diameter of the largest tumour was measured directly in patients with hepatic resection. In patients with unresectable disease, the diameter of the tumour was measured radiologically by computed tomography scan, angiography or ultrasonography. The American Joint Committee on Cancer tumour, node, metastasis (TNM) staging system was used for clinical and pathological staging.30

Selection criteria for surgery

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

The criteria of resectability were the same over the study period, and included liver function and indocyanine green test, the absence of distant metastasis, anatomically resectable disease and the absence of main portal vein or inferior vena cava tumour thrombus. Age was not a selection criterion for or against surgical resection.

Surgical treatment group

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

The pre-operative investigations, operative technique and post-operative management have been documented elsewhere.31,32 After surgery, all patients were followed up regularly at intervals of 1–3 months with physical examination, serum α-foetoprotein concentration assay and liver biochemistry tests. Computed tomography of the liver was performed if clinically indicated. Patients with anatomically resectable intra-hepatic recurrence and adequate liver functional reserve were managed by re-resection. Patients with unresectable intra-hepatic recurrences were managed by either transcatheter arterial chemo-embolization or percutaneous ethanol injection therapy. Isolated extra-hepatic recurrence or pulmonary recurrence was managed with surgical resection if possible.

Management of inoperable patients

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

Patients with unresectable disease were offered transcatheter arterial chemo-embolization, percutaneous ethanol injection, oral tamoxifen, cryotherapy or radiofrequency ablation therapy. In general, patients with unresectable intra-hepatic disease and adequate hepatic functional reserve with no portal vein occlusion or arterio-venous shunting were offered transcatheter arterial chemo-embolization treatment.

Statistics

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

Statistical analysis was performed using the chi-squared test and Fisher's exact test for discrete variables. The Mann–Whitney U-test and Student's t-test were used for continuous ordinal variables. Survival curves were calculated by the Kaplan–Meier method and comparison was made with the log-rank test. In all cases, survival was calculated from the date of operation to the date of the most recent follow-up examination or to the date of death. A two-tailed test with a P value of 0.05 or less was considered to be statistically significant.

Clinical parameters

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

The mean age of the young group was 29.6 years (range, 13–40 years) and that of the old group was 58.4 years (range, 41–88 years). The male to female ratios were 4.5/1 and 6.3/1 for the young and old groups, respectively. A smoking history was significantly more prevalent in the old group than in the young group (834/1724 vs. 34/120, P < 0.0001). The same was also true for a history of alcohol (503/1673 vs. 26/118, P < 0.0001). As expected, the old age group had a higher co-morbidity rate (44%, 770/1742) than the young group (23%, 28/121) (P < 0.0001), but the prevalence of associated malignancies did not differ between the two groups [2.1% (36/1741) vs. 0.8% (1/121)] (P = 0.3).

A family history of a first-degree relative with hepatocellular carcinoma was found in 24% (26/107) of the young group and in 15% (233/1560) in the old group (P = 0.01). More young patients than old patients were aware of their hepatitis B carrier state [74% (87/118) vs. 62% (1060/1713)] (P < 0.01). More old patients than young patients were known to have cirrhosis clinically [181/1435 (13%) vs. 1/98 (1%)] (P < 0.0001).

The presenting symptoms and physical signs are summarized in Table 1. In general, young patients presented more often with pain (78/114 vs. 849/1682, P < 0.0001), hepatomegaly (78/120 vs. 914/1723, P = 0.01) and ruptured hepatocellular carcinoma (8/118 vs. 46/1709, P = 0.02), whereas the old age group presented more often with symptoms and signs of cirrhosis, such as ankle oedema (240/1692 vs. 5/118, P = 0.001) and ascites (324/1720 vs. 10/120, P = 0.002). Hepatocellular carcinoma in old patients was more likely to be detected incidentally by routine screening by α-foetoprotein, ultrasound or computed tomography scan [12.1% (211/1737) vs. 5.8% (7/121)] (P = 0.035).

Table 1.  Comparison of the presenting symptoms, physical signs and blood biochemistry in young and old patients with hepatitis B virus-related hepatocellular carcinoma (HCC)
 Young patients (%) (n = 121)Old patients (%) (n = 1742)P valueCI
Clinical presentation
 Pain78/114 (68)849/1682 (51)< 0.0001
 Ankle swelling0 (0)34/1737 (2)0.03
 Ruptured HCC8/118 (7)46/1709 (3)0.02
Physical signs
 Ankle oedema5/118 (4)240/1692 (14)0.001
 Hepatomegaly78/120 (65)914/1723 (53)0.01
 Moderate to gross ascites10/120 (8)324/1720 (19)0.002
Blood biochemistry
 Haemoglobin (g/dL)13.812.9< 0.0001− 1.3, − 0.48
 Platelets (109/L)200164< 0.0001− 60.1, − 22.1
 Urea (mmol/L)4.35.3< 0.00010.95, 2.18
 Creatinine (µmol/L)8591< 0.00013.1, 17.0
 Total bilirubin (µmol/L)14170.003− 3.3, 22.27
 Albumin (g/L)4237< 0.0001− 5.79, − 3.36
 Globulin (g/L)3236< 0.00012.59, 5.49
 Prothrombin time (s)12.613.5< 0.00010.16, 1.67
Child–Pugh grading
 A1041187< 0.0001 
 B13344  
 C1132  

Liver function study and other blood tests

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

The differences in blood tests taken before treatment are shown in Table 1. A lower haemoglobin concentration and higher serum urea and creatinine concentrations were found in the old group. Furthermore, in these patients, the findings of a lower platelet count and serum albumin concentration, higher serum bilirubin and globulin concentrations and a longer prothrombin time suggested the development of liver cirrhosis. The liver function, as reflected by Child–Pugh grading, was significantly better preserved in the young than in the old age group (P < 0.0001). The indocyanine green excretion test was performed in all patients who had undergone surgical resection. The median value of indocyanine green retention at 15 min was 7.6% (range, 2.1–16%) in young patients and 11.1% (range, 1.2–66.9%) in old patients (P < 0.0001). Hepatitis C infection was only found in 3% (14/462) of hepatitis B virus patients and there was no difference between the two groups.

Tumour status and treatment received

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

Although more young patients than old patients [83/116 (72%) vs. 1006/1742 (58%)] (P = 0.003) had fully active pre-treatment general status, pre-operative investigations showed that young patients (12/58, 20.7%) had more pulmonary metastasis on presentation than old patients (97/999, 9.7%) (P = 0.008). The mean pre-operative α-foetoprotein concentration was also significantly higher in young patients (163 868 ± 340 965 ng/mL) than in old patients (53 812 ± 238 334 ng/mL) (P = 0.001). In addition, the largest tumour was greater in young patients than in old patients (9.4 ± 5.6 cm vs. 7.6 ± 3.8 cm) (P = 0.001); the same was true for the largest tumour width (9.6 ± 4.6 cm vs. 7.6 ± 3.8 cm) (P = 0.001). Despite the more frequent pulmonary metastasis, higher α-foetoprotein concentration and larger tumour size in young patients, the resectability rate was similar in the two groups [young patients (40/119, 33.6%) vs. old patients (483/1725, 28%)] (P < 0.19).

When the reasons for unresectability were compared, it was obvious that the young age group showed more advanced tumours (78% in young vs. 63% in old patients; P = 0.006), whereas poor functional reserve of the liver was more commonly observed in the old age group (7.6% in young vs. 17.6% in old patients; P = 0.02).

On the other hand, the resectability rate was much higher in both young and old patient groups with hepatocellular carcinoma detected during routine screening [young: 25% vs. 8%, P = 0.014; old: 53% vs. 47%, P < 0.0001].

Pathology of resected specimen

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

There was no statistically significant difference between young and old age groups with regard to: (i) the presence of venous infiltration (young 50% vs. old 45.8%; P = 0.6); (ii) encapsulation of the tumour (young 29% vs. old 43.2%; P = 0.09); and (iii) TNM staging (stage I : II : III and above: young 3 : 14 : 23 vs. old 34 : 175 : 274; P = 0.99) with resectable disease. The non-tumorous part of the liver was either cirrhotic or hepatitic in 87.5% of young and 94.6% of old patients (P = 0.06). However, the presence of cirrhotic change in the non-tumorous part did not differ between the two groups (53% vs. 56%, P = 0.7). The similar rate of cirrhosis in resected specimens was probably due to the fact that patients with high-grade cirrhosis were probably inoperable. Edmondson grading was assessed in 154 hepatocellular carcinoma specimens, but no difference was observed between the two groups (P = 0.6).

Survival rates

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

There was no significant difference between the two groups of patients in terms of the overall survival rate (median survival was 6.6 months in young vs. 8.3 months in old patients, P = 0.77). In patients who underwent surgical resection, the post-resection overall median survival (51.9 months in young vs. 42.5 months in old patients) and the disease-free survival (9.2 months in young vs. 16.1 months in old patients) were also similar.

However, when the groups of patients with unresectable disease were compared, the median survival for young patients (3.6 months) was significantly shorter than that for old patients (4.6 months) (P = 0.004) (Figure 1).

image

Figure 1. A statistically significant difference in survival was observed between young and old patients with unresectable hepatocellular carcinoma.

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Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References

Hepatitis B virus infection is the main cause of hepatocellular carcinoma, especially in the Chinese population. We therefore focused on hepatocellular carcinoma in young and old patients who were infected with hepatitis B virus. Our study indicates that young and old patients with hepatocellular carcinoma present differently. Young patients, despite being more aware of their hepatitis B carrier status, usually present late with pain and hepatomegaly, and at a more advanced stage with frequent pulmonary metastasis. In addition, this group of patients has a higher prevalence of a family history of hepatocellular carcinoma. On the other hand, old patients are more frequently detected during routine screening or present with features of cirrhosis. Habitual factors causing cirrhosis, such as drinking, are more common in these patients. Hence, the reported differences in clinico-pathological characteristics in these two groups of patients are probably due to the different clinical presentation and screening strategy.

In this study, the prognosis of young patients with unresectable hepatocellular carcinoma was extremely poor and was even worse than that of their older counterparts. This, together with the late presentation but high resectability rate in this group, suggests that early detection, such as by screening, could be beneficial. Two consensus development conferences held in the USA33 and Italy34 have concluded that chronic carriers of hepatitis B virus, patients with cirrhosis and patients with rare metabolic liver diseases should be recommended for periodic screening. Furthermore, it has been recommended that cirrhotic patients and those with certain congenital metabolic conditions known to be risk factors for hepatocellular carcinoma should be screened by α-foetoprotein and ultrasonography twice a year.34 The implementation of an early screening programme for this group of patients might lead to the detection of disease at an earlier stage and improve the resectability rate.35 Recently, it has been reported that young hepatitis B virus patients might benefit even more from screening,36 and that routine screening should be implemented in young patients, especially those with a positive family history.37 The current study further supports this view, and we wish to re-emphasize that young hepatitis B virus patients should not be neglected and should be screened. However, further studies are necessary to determine the cost-effectiveness, as only a small group of patients may benefit.

Our study may also help to clarify the controversy over the prognosis of young patients with hepatocellular carcinoma. The age of a patient in various malignancies is an important prognostic factor. In breast38 and colorectal39 cancer, a young age is associated with a poorer prognosis. In contrast, in transitional cell carcinoma of the bladder40 and papillary cell carcinoma of the thyroid,41 young patients have a much better prognosis than their older counterparts. For hepatocellular carcinoma, the relationship between age and prognosis is controversial. Ni et al. found a lower resectability rate and a poorer outcome for children (3–17 years) suffering from hepatocellular carcinoma.42 Ng et al. reported a higher percentage of venous permeation and liver invasion and a lower percentage of cirrhosis and encapsulation of the tumour in young patients (< 50 years) with resectable hepatocellular carcinoma, but there was no difference in survival rate after surgical resection.28 In our study, the overall survival and survival after surgical resection were no different in young and old patients. However, the survival rate of young patients with unresectable disease was significantly worse than that of old patients. These data suggest that young patients present with more advanced disease than their older counterparts. Reasons for the more advanced disease in young patients may be the late awareness of symptoms by patients or attending physicians, a different aggressiveness of the disease, or both.

Our study has demonstrated several very different clinico-pathological characteristics in young patients with hepatitis B virus-related hepatocellular carcinoma. The differences probably relate to a poor awareness of the disease in this age group by both patients and doctors. As the prognosis of young patients with unresectable hepatocellular carcinoma is significantly worse than that of their older counterparts, we suggest that young patients who are carriers of hepatitis B surface antigen should be recruited into the screening programme, especially when they have a positive family history of hepatocellular carcinoma.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and methods
  5. Diagnosis and staging of hepatocellular carcinoma
  6. Selection criteria for surgery
  7. Surgical treatment group
  8. Management of inoperable patients
  9. Statistics
  10. Results
  11. Clinical parameters
  12. Liver function study and other blood tests
  13. Tumour status and treatment received
  14. Pathology of resected specimen
  15. Survival rates
  16. Discussion
  17. Acknowledgements
  18. References
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