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  1. Journal Meeting 時間: AM 07:30 日期: 06/29/2007 地點: 胸腔外科辦公室 報告人: R2 許博順

  2. Pulmonary resection for metastases from hepatocellular carcinoma: Factors influencing prognosis • The Journal of Thoracic and Cardiovascular Surgery, June 2006 • Takahito Nakagawa, MD, Toshiya Kamiyama, MD, Kazuaki Nakanishi, MD, Hideki Yokoo, MD, Hirofumi Kamachi, MD, Michiaki Matsushita, MD, Satoru Todo, MD • Department of General Surgery, Hokkaido University, Graduate School of Medicine, Sapporo, Japan.

  3. Introduction • highly fatal cancer • common in Taiwan and Japan, increasing incidence in the world • reduced the operative morbidity and mortality • long-term outcome: poor because high incidence of recurrence • Recurrence: most common in the liver, extra-hepatic in the lung

  4. Surgical resection of pulmonary metastases from HCC • Indications?? • Prognostic factors?? • This paper analyzes the clinical factors and outcome.

  5. Abbreviations and Acronyms • AFP: alpha-fetoprotein • DFI: disease-free interval • HCC: hepatocellular carcinoma • TACE: trans-arterial chemoembolization • RFA: radiofrequency ablation • PEIT: percutaneous ethanol injection therapy

  6. Methods • From January 1987 to December 2003 • 544 underwent partial hepatectomy: 12 died, 532 were followed with a interval of 3 months by CxR, serum AFP and abd CT • Chest CT was performed if AFP level increase or significant finding on CxR

  7. Criteria for pulmonary resection • Uncontrollable intrahepatic disease • No metastatic disease at another site • CT demonstrating that complete resection could be performed regardless of the number of lesions • Bilateral pulmonary metastasis: no contraindication • Additional lung metastases after metastectomy: no contraindication • Uncontrolled liver disease or unresectable multiple lung metastases were offered chemotherapy • Uncontrolled liver disease: criteria ??

  8. wedge resection was the procedure of choice • LN dissection was not undertaken • disease-free interval (DFI): last curative treatment for intrahepatic disease and the detection of pulmonary deposits

  9. Statistics • chi-square test was used to compare categoric variables between the 2 groups • unpaired t test was used to compare continuous variables • Survival was estimated by the Kaplan-Meier method • differences between survival curves were tested by the log-rank test • 1 patient died in the early postoperative period

  10. Results

  11. after C/T

  12. Pulmonary metastasectomy • Twenty-five patients • Wedge resection: 21 • Lobectomy: 2 • Lobectomy and wedge: 1 • Bilateral lobectomy: 1 • Second wedge: 6 • Thrid wedge: 1

  13. Mortality • One died of pyothorax 19 days after lobectomy (mortality rate: 3.1%) • Ten died of HCC recurrence • One died sepsis 59 months after metastasectomy

  14. median follow-up: 37.3 months (range, 0.6-177.4 months) • median survival: 51.8 months • 1-year survival rate: 80% +/- 8%, • 3-year survival rate: 61% +/- 10%, • 5-year survival rate: 36% +/- 13%

  15. Three survived more than 5 years • Case 1: bilateral residual tumors after chemotherapy, underwent RUL and LLL lobectomy Alive with no recurrence at 177 months • Case 3: wedge resection after a DFI of 22 months, and 32 months. Alive at 142 months without evidence of recurrence • Case 11: wedge resection 3 times at 27,33, and 45 months after right hepatectomy hepatic recurrence managed with TACE 2 years later and disease-free at 25 months after TACE

  16. tumor number (solitary or multiple) or tumor distribution (unilateral or bilateral lung): no significant effect

  17. Mean DFI: 16.3 months (range, 1-37 months). • 10 patients had a DFI of 1 to 11 months mean survival was 30.6 months • 14 patients had a DFI > 12 months mean survival was 35.4 months • P=.117

  18. 19 patients: AFP levels < 500 ng/mL • Mean survival:39.2 months. • 5 patients: AFP levels > 500 ng/mL • Mean survival: 15.9 months • P=.225

  19. Group 1: low-risk (DFI>12 months and AFP<500ng/ml) 3-year survival: 89% +/- 11% 5-year survival: 74% +/- 16% • Group 2: high-risk (DFI<12 months or AFP>500ng/ml) 3-year survival: 42% +/- 14% 5-year survival: 21% +/- 16%

  20. Incidences of intrahepatic recurrence and pulmonary re-recurrence did not differ between the low- and high-risk groups • Incidence of metastases to other organs was significantly higher in the high-risk group than in the low-risk group (P .003,chi-square test)

  21. Discussion

  22. Prognosis Predictor • DFI was an important prognostic factor • Long-term follow-up of operative treatment for pulmonary metastases. Eur J Cardiothorac Surg. 1989;3:292-6. • Analysis of prognostic factors in patients undergoing resection of pulmonary metastases from soft tissue sarcomas. J Thorac Cardiovasc Surg. 1984;87:260-8. • DFI > 36 months is a good prognostic factor in colorectal cancer or breast cancer. • Pulmonary resection for metastases from colorectal cancer: factors influencing prognosis. Twenty-year experience. Eur J Cardiothorac Surg. 2002;21:906-12. • Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the international registry of lung metastases. Eur J Cardiothorac Surg. 2002;22:335-44.

  23. Prognosis Predictor • CEA level is a significant predictor factor in pulmonary metastases from colorectal cancer. • Pulmonary resection for metastases from colorectal cancer: factors influencing prognosis. Twenty-year experience. Eur J Cardiothorac Surg. 2002;21:906-12 • AFP level is significant prognostic factor • Cutoff points: 400 ng/dl • A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: The Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28:751-5 • Cutoff points: 1000 ng/dl • Prognostic factors after hepatic resection for hepatocellular carcinoma with hepatitis C viral infection: univariate and multivariate analysis. Am J Gastroenterol. 2001;96:1243-50. • AFP level showed close correlation with multiple tumor, larger size, macroscopic invasion, poor differentiation and 3-year recurrence rates • Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg. 2004;240:451-9.

  24. MELD Score=0.957 × Loge(creatinine mg/dL) + 0.378 Loge(bilirubin mg/dL) + 1.120 × Loge (INR) + 0.643

  25. Conclusion • DFI of more than 1 year and a serum AFP < 500 ng/mL together predict a better outcome after pulmonary metastasectomy of HCC • Bilateral or unilateral is no contraindication • Single or multiple is no contraindication

  26. RFA • cirrhosis and HCC (Child-Pugh class A, 50; B, 31; C, 29), 110 patients were treated. The complication rate was 13%, with local recurrence developing in only 4% at a follow-up of 19 months, although in a large number of patients, recurrent disease developed at other sites within the liver • Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg2000;232:381-391