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JACS CME-1 Featured Article, Volume 204, May 2007
CONTINUING MEDICAL EDUCATION PROGRAM
JACS CME-1 FEATURED ARTICLE, VOLUME 204, MAY 2007 Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy Mullen JT, Ribero D, Reddy S, et al J Am Coll Surg 2007;204:854–862 Outcome of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment Vauthey J-N, Ribero D, Abdalla EK, et al J Am Coll Surg 2007;204:1016–1027 Objectives: After reading the featured articles published in this issue of the Journal of the American College of Surgeons (JACS) participants in the JACS CME program should be able to demonstrate increased understanding of the material specific to the article featured and be able to apply relevant information to clinical practice. Objectives are stated at the beginning of each featured article; the questions follow with five response choices, and a critique discussing the objective. The American College of Surgeons is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The JACS CME program fulfills the ACCME essentials. The American College of Surgeons designates this educational activity for a maximum of 2 Category 1 credits toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/ she actually spent in the educational activity.
You can earn 4 CME credits using JACS CME Online, at http://jacscme.facs.org, or you can earn 2 CME credit if you submit this page by fax (see instructions in box below). JACS CME Online provides four articles from each issue for 4 credits per month. The articles this month on JACS CME Online are: Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy. Mullen JT, Ribero D, Reddy S, et al. Outcome of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment. Vauthey J-N, Ribero D, Abdalla EK, et al. Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. Parks R, Gonen M, Kemeny N, et al. Laparoscopic heller myotomy with anterior fundoplication ameliorates Symptoms of achalasia in pediatric patients. Paidas CN, Cowgill SM, Boyle R, et al.
Questions: Wendy Cowles Husser, MA, MPA Executive Editor, JACS 633 N Saint Clair Street, Chicago, IL 60611 312-202-5306 (ph) 312-202-5027 (fax) [email protected]
© 2007 by the American College of Surgeons Published by Elsevier Inc.
1081
ISSN 1072-7515/07/$32.00 doi:10.1016/j.jamcollsurg.2007.02.058
1082
Continuing Medical Education Program
Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy
Mullen JT, Ribero D, Reddy S, et al J Am Coll Surg 2007;204:854–862
Learning Objectives: After review of this article, the surgeon will be able to describe the proposed definition of postoperative hepatic insufficiency (PHI) as well as the significant predictors of morbidity and mortality in noncirrhotic patients undergoing major hepatectomy. Question 1
Which of the following biochemical criteria is proposed in this study as a reliable definition of postoperative hepatic insufficiency (PHI) in noncirrhotic patients undergoing major hepatectomy? Peak postoperative INR (PeakINR) ⬎ 2.0. Peak postoperative bilirubin (PeakBil) ⬎ 7.0. Serum bilirubin ⬎ 50 ml/L on postoperative day 5. Prothrombin time ⬍ 50% normal on postoperative day 5. e) “50-50 criteria” on postoperative day 5.
a) b) c) d)
Critique: The PeakINR cut-off value of 2.0 is not an independent predictor of morbidity and is a less accurate predictor of liver failure-related death than the PeakBil cut-off value of 7.0 mg/dL. This is likely because the kinetics of the INR changes after major hepatectomy are variable in the first few postoperative days and the fact that the postoperative INR value is affected by the intraoperative and early postoperative administration of fresh frozen plasma. The results of this study confirm that PeakBil ⬎ 7.0 mg/dL is the most powerful predictor of any complication, a major complication, 90-day all-cause mortality, and 90-day liverrelated mortality after major hepatectomy. Though not all patients who meet this criterion after major hepatectomy will die, the vast majority of patients with a PeakBil ⬎ 7.0 mg/dL will suffer a major complication and thus a prolonged hospital stay. Accordingly, we propose to define PHI as a PeakBil ⬎ 7.0 mg/dL. Using the “50-50 criteria” or its individual components (prothrombin time [PT] ⬍ 50% and serum bilirubin [SB] ⬎ 50 ml/L) on postoperative day five after hepatic resection underestimates the true incidence of PHI by nearly two-fold. Question 2
Which of the following statements concerning the risk of death from liver failure after major hepatectomy is correct? a) Younger age is associated with an increased risk of death from liver failure after major hepatectomy. b) The performance of a concomitant major intraabdomi-
J Am Coll Surg
nal procedure at the time of hepatectomy is not associated with an increased risk of death from liver failure. c) More than 25% of deaths due to liver failure after major hepatectomy do not meet the traditional criteria of 30day postoperative mortality. d) The median time to death from liver failure after major hepatectomy is approximately 14 days. e) Contemporary reports of zero or near-zero mortality rates after liver resection probably accurately reflect the true risk of major hepatectomy.
Critique: Older age and the performance of an associated major intraabdominal procedure at the time of major hepatectomy are independent predictors of morbidity and 90day all-cause and liver-related mortality. When considering hospital discharges and deaths beyond 30 days and until 90 days after liver resection, nearly 33% (16/50) of all deaths and more than 25% (8/30) of deaths due to liver failure would not have met the traditional criteria for postoperative mortality. Indeed, in this study, the median time to death from liver failure was 36 days. Accordingly, the standard definition of postoperative mortality after liver resection should include all deaths out to a minimum of 90 days after surgery in order to accurately reflect the true risk of major hepatectomy, which is almost certainly underestimated by the many contemporary reports of zero or nearzero mortality rates after liver resection. Outcome of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment
Vauthey J-N, Ribero D, Abdalla EK, et al J Am Coll Surg 2007;204:1016–1027
Learning Objectives: After review of this article, the surgeon will be able to describe the various stagings for hepatocellular carcinoma as well as the significant predictors of survival after resection and transplantation for hepatocellular carcinoma. Question 1
Among the stagings proposed for evaluation of hepatocellular carcinoma which staging has been evaluated and validated in multicenter studies after resection and transplantation for hepatocellular carcinoma? a) Liver Cancer Study Group of Japan staging system. b) United Network for Organ Sharing modified staging system. c) Pittsburgh scoring system. d) American Joint Committee on Cancer 6th edition staging system. e) Barcelona Clinic Liver Cancer classification.
Vol. 204, No. 5, May 2007
Critique: The American Joint Committee on Cancer 6th edition staging system has been evaluated in multicenter studies in patients undergoing resection and liver transplantation for hepatocellular carcinoma. Liver transplantation enables the best possible evaluation of staging for hepatocellular carcinoma because it provides a complete evaluation of the extension of tumor in the entire liver and eliminates the confounding effect on prognosis associated with the underlying liver disease. Previous studies have compared different staging systems for hepatocellular carcinoma in heterogeneous cohort of patients treated with various modalities. The pathologic evaluation of the entire explanted liver reduces the potential risk of understaging the disease and as a consequence the risk of stage migration. Question 2
The American Joint Committee on Cancer 6th edition staging system stratifies patients based on the following factors of prognosis: a) Tumor number (single versus multiple), tumor size (cut-off 2 cm) and vascular invasion. b) Tumor number (single versus multiple), tumor grade and satellites. c) Tumor number (single versus multiple), tumor size (cut-off 5 cm) and vascular invasion. d) One nodule up to 5 cm, three nodules up to 3 cm.
Continuing Medical Education Program 1083
Critique: The American Joint Committee on Cancer 6th edition staging system for hepatocellular carcinoma is based on the presence or absence and the extent of vascular invasion, tumor number (single versus multiple, and tumor size (cut-off 5 cm). This staging system was developed based on a Japanese proposal using macroscopic evaluation of pathological specimens following resection of hepatocellular carcinoma. Subsequently several single center and multicenter studies indicated that microscopic and macroscopic vascular invasion were the main factors of prognosis after resection and transplantation for hepatocellular carcinoma. The American Joint Committee on Cancer 6th edition staging system for hepatocellular carcinoma has been validated in large Eastern and Western series reporting on patients undergoing hepatic resection. The finding that the same pathologic staging system effectively defines the prognosis after hepatic resection and liver transplantation confirms the powerful effect of vascular invasion which has been shown as an independent prognostic factor of outcome after resection and transplantation for hepatocellular carcinoma. The American Joint Committee on Cancer 6th edition staging system is recommended for the use in patients with preserved liver function. It can be used clinically (cTNM) prior to surgery or pathologically (pTNM) following surgery.
JACS CME-1 FEATURED ARTICLE, VOLUME 204, MAY 2007 Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy Mullen JT, Ribero D, Reddy S, et al J Am Coll Surg 2007;204:854–862 Outcome of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment Vauthey J-N, Ribero D, Abdalla EK, et al J Am Coll Surg 2007;204:1016–1027 Objectives: After reading the featured articles published in this issue of the Journal of the American College of Surgeons (JACS) participants in the JACS CME program should be able to demonstrate increased understanding of the material specific to the article featured and be able to apply relevant information to clinical practice. Objectives are stated at the beginning of each featured article; the questions follow with five response choices, and a critique discussing the objective. The American College of Surgeons is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The JACS CME program fulfills the ACCME essentials. The American College of Surgeons designates this educational activity for a maximum of 2 Category 1 credits toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/ she actually spent in the educational activity.
You can earn 4 CME credits using JACS CME Online, at http://jacscme.facs.org, or you can earn 2 CME credit if you submit this page by fax (see instructions in box below). JACS CME Online provides four articles from each issue for 4 credits per month. The articles this month on JACS CME Online are: Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy. Mullen JT, Ribero D, Reddy S, et al. Outcome of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment. Vauthey J-N, Ribero D, Abdalla EK, et al. Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. Parks R, Gonen M, Kemeny N, et al. Laparoscopic heller myotomy with anterior fundoplication ameliorates Symptoms of achalasia in pediatric patients. Paidas CN, Cowgill SM, Boyle R, et al.
Questions: Wendy Cowles Husser, MA, MPA Executive Editor, JACS 633 N Saint Clair Street, Chicago, IL 60611 312-202-5306 (ph) 312-202-5027 (fax) [email protected]
© 2007 by the American College of Surgeons Published by Elsevier Inc.
1081
ISSN 1072-7515/07/$32.00 doi:10.1016/j.jamcollsurg.2007.02.058
1082
Continuing Medical Education Program
Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy
Mullen JT, Ribero D, Reddy S, et al J Am Coll Surg 2007;204:854–862
Learning Objectives: After review of this article, the surgeon will be able to describe the proposed definition of postoperative hepatic insufficiency (PHI) as well as the significant predictors of morbidity and mortality in noncirrhotic patients undergoing major hepatectomy. Question 1
Which of the following biochemical criteria is proposed in this study as a reliable definition of postoperative hepatic insufficiency (PHI) in noncirrhotic patients undergoing major hepatectomy? Peak postoperative INR (PeakINR) ⬎ 2.0. Peak postoperative bilirubin (PeakBil) ⬎ 7.0. Serum bilirubin ⬎ 50 ml/L on postoperative day 5. Prothrombin time ⬍ 50% normal on postoperative day 5. e) “50-50 criteria” on postoperative day 5.
a) b) c) d)
Critique: The PeakINR cut-off value of 2.0 is not an independent predictor of morbidity and is a less accurate predictor of liver failure-related death than the PeakBil cut-off value of 7.0 mg/dL. This is likely because the kinetics of the INR changes after major hepatectomy are variable in the first few postoperative days and the fact that the postoperative INR value is affected by the intraoperative and early postoperative administration of fresh frozen plasma. The results of this study confirm that PeakBil ⬎ 7.0 mg/dL is the most powerful predictor of any complication, a major complication, 90-day all-cause mortality, and 90-day liverrelated mortality after major hepatectomy. Though not all patients who meet this criterion after major hepatectomy will die, the vast majority of patients with a PeakBil ⬎ 7.0 mg/dL will suffer a major complication and thus a prolonged hospital stay. Accordingly, we propose to define PHI as a PeakBil ⬎ 7.0 mg/dL. Using the “50-50 criteria” or its individual components (prothrombin time [PT] ⬍ 50% and serum bilirubin [SB] ⬎ 50 ml/L) on postoperative day five after hepatic resection underestimates the true incidence of PHI by nearly two-fold. Question 2
Which of the following statements concerning the risk of death from liver failure after major hepatectomy is correct? a) Younger age is associated with an increased risk of death from liver failure after major hepatectomy. b) The performance of a concomitant major intraabdomi-
J Am Coll Surg
nal procedure at the time of hepatectomy is not associated with an increased risk of death from liver failure. c) More than 25% of deaths due to liver failure after major hepatectomy do not meet the traditional criteria of 30day postoperative mortality. d) The median time to death from liver failure after major hepatectomy is approximately 14 days. e) Contemporary reports of zero or near-zero mortality rates after liver resection probably accurately reflect the true risk of major hepatectomy.
Critique: Older age and the performance of an associated major intraabdominal procedure at the time of major hepatectomy are independent predictors of morbidity and 90day all-cause and liver-related mortality. When considering hospital discharges and deaths beyond 30 days and until 90 days after liver resection, nearly 33% (16/50) of all deaths and more than 25% (8/30) of deaths due to liver failure would not have met the traditional criteria for postoperative mortality. Indeed, in this study, the median time to death from liver failure was 36 days. Accordingly, the standard definition of postoperative mortality after liver resection should include all deaths out to a minimum of 90 days after surgery in order to accurately reflect the true risk of major hepatectomy, which is almost certainly underestimated by the many contemporary reports of zero or nearzero mortality rates after liver resection. Outcome of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment
Vauthey J-N, Ribero D, Abdalla EK, et al J Am Coll Surg 2007;204:1016–1027
Learning Objectives: After review of this article, the surgeon will be able to describe the various stagings for hepatocellular carcinoma as well as the significant predictors of survival after resection and transplantation for hepatocellular carcinoma. Question 1
Among the stagings proposed for evaluation of hepatocellular carcinoma which staging has been evaluated and validated in multicenter studies after resection and transplantation for hepatocellular carcinoma? a) Liver Cancer Study Group of Japan staging system. b) United Network for Organ Sharing modified staging system. c) Pittsburgh scoring system. d) American Joint Committee on Cancer 6th edition staging system. e) Barcelona Clinic Liver Cancer classification.
Vol. 204, No. 5, May 2007
Critique: The American Joint Committee on Cancer 6th edition staging system has been evaluated in multicenter studies in patients undergoing resection and liver transplantation for hepatocellular carcinoma. Liver transplantation enables the best possible evaluation of staging for hepatocellular carcinoma because it provides a complete evaluation of the extension of tumor in the entire liver and eliminates the confounding effect on prognosis associated with the underlying liver disease. Previous studies have compared different staging systems for hepatocellular carcinoma in heterogeneous cohort of patients treated with various modalities. The pathologic evaluation of the entire explanted liver reduces the potential risk of understaging the disease and as a consequence the risk of stage migration. Question 2
The American Joint Committee on Cancer 6th edition staging system stratifies patients based on the following factors of prognosis: a) Tumor number (single versus multiple), tumor size (cut-off 2 cm) and vascular invasion. b) Tumor number (single versus multiple), tumor grade and satellites. c) Tumor number (single versus multiple), tumor size (cut-off 5 cm) and vascular invasion. d) One nodule up to 5 cm, three nodules up to 3 cm.
Continuing Medical Education Program 1083
Critique: The American Joint Committee on Cancer 6th edition staging system for hepatocellular carcinoma is based on the presence or absence and the extent of vascular invasion, tumor number (single versus multiple, and tumor size (cut-off 5 cm). This staging system was developed based on a Japanese proposal using macroscopic evaluation of pathological specimens following resection of hepatocellular carcinoma. Subsequently several single center and multicenter studies indicated that microscopic and macroscopic vascular invasion were the main factors of prognosis after resection and transplantation for hepatocellular carcinoma. The American Joint Committee on Cancer 6th edition staging system for hepatocellular carcinoma has been validated in large Eastern and Western series reporting on patients undergoing hepatic resection. The finding that the same pathologic staging system effectively defines the prognosis after hepatic resection and liver transplantation confirms the powerful effect of vascular invasion which has been shown as an independent prognostic factor of outcome after resection and transplantation for hepatocellular carcinoma. The American Joint Committee on Cancer 6th edition staging system is recommended for the use in patients with preserved liver function. It can be used clinically (cTNM) prior to surgery or pathologically (pTNM) following surgery.