Limitations in liver resection: Is preoperative chemotherapy limiting the extent of liver resection?...
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Transcript of Limitations in liver resection: Is preoperative chemotherapy limiting the extent of liver resection?...
Limitations in liver resection:
Is preoperative chemotherapy limiting the extent of liver resection?
Jürgen KlempnauerDepartment of General, Visceral and Transplantation Surgery
Medizinische Hochschule Hannover, Germany
Typical chemotherapeutic agentsa hepatobiliary surgeon is confronted with
Adjuvant colon / rectal cancer treatment after resection of primary site *:5-FU + leucovorin
CapecitabineFOLFOX
* NCCN + American Cancer Society: Colon and Rectal Cancer Treatment Guidelines – Version IV, February 2005
Most patients that have been exposed to chemotherapyprior to liver resection had adjuvant chemotherapy
after resection of a colorectal primary tumor.
Hepatotoxicity of Chemotherapy
Toxic liver injury can reproduce virtually any known pattern of injury:
- necrosis- steatosis- fibrosis- cholestasis- vascular injury
* King and Perry (2001); Oncologist 6:162-176
All chemotherapeutic agents have the potentialto cause liver injury *.
Hepatotoxicity:Common toxicity criteria of the National Cancer Institute, version 2.0
Preoperative assessment of liver functionto tailor the appropriate extent of resection
Requirements of tumor freeresection margins.Any underlying hepatic
functional impairmentthat tends to limit
the safe extent of resection.
Tests of liver function to assess hepatic reserve *
Clearance / tolerance testsaminopyrine breath testindocyanine (ICG) retention (clearance)bromosulphalein (BSP) retentiongalactose tolerancebile acid tolerancebeta-hydroxy butyrate/acetoacetate
Functional imaging and blood flow: uptake/clearancereticuloendotheliumsulfur colloidbiliary excretionrose bengalhepatic diacetic acid (HIDA)receptor targetingneogalactosyl albumin (NGA)galactosyl serum albumin (GSA)
* Schneider (2004). Surg Clin N Am 84:355-73
No single test appears to account for the variability of clinical resection results.
No existing test has proven better than the Child-Pugh-Classificationfor assessing hepatic reserve.
Child-Pugh Score
Clinical or biochemical measurement
Points scored
1 2 3
Encephalopathy grade
None 1-2 3-4
Ascites Absent Mild Moderate to severe
Bilirubin <35 µmol/l 36-60 µmol/l >60 µmol/l
Albumin >35 g/l 28-35 g/l <28 g/l
[INR] [<1-7] [1.7-2.3] [>2.3]
Child-Pugh A Score < 6, Child-Pugh B Score 7-9, Child-Pugh C Score >10
Integration of anatomical and functional imaging modalitiesmay improve properative assessment of hepatic reserve in the future.
Chemotherapy and Liver Regeneration
Schrem et al. (2004); Pharmacol Rev. 56(2):291-330
Interference withcell cycle progression
by chemotherapy.
Decreasing ability forliver regeneration and
restoration of liver function.
Hepatic resections trigger functional andparenchymal liver regeneration.
Hepatocytes switch from the quiescent stateinto cell cycle progression followed by cell division and
liver regrowth after resection.
Possible limitations of liver resection bypreoperative chemotherapy
Chemotherapy can leadto toxic liver injury.
Negative impacton hepatic reserve.
Chemotherapy compromisespostoperative liver regeneration.
Wait at least 4 – 6 weeks after chemotherapybefore any planned liver resection !
„Wash-out phase of toxic agents“
Extended Hepatectomy
Recommended minimal functional remnant liver volumes:
≥ 25 % in normal livers
≥ 40 % in livers with- moderate to severe steatosis,- cholestasis,- fibrosis or cirrhosis,- following chemotherapy.
Tucker and Heaton (2005). Curr Opin Critical Care 11:150-155Shoup et al. (2003). J Gastrointestinal Surg 7:325-330
Vauthey et al. (2000). Surgery 127: 512-519
Small for Size Liver Syndrome (SFSS)
Insufficient functional liver massafter liver transplantation or extended hepatectomy.
Postoperative liver dysfunction with:- prolonged cholestasis- coagulopathy- portal hypertension- ascites
Predisposes to:Sepsis, GI bleeding, intestinal perforation, encephalopathy, mortality
Small for Size Liver Syndrome (SFSS)
Preoperative Portal Vein Embolization (PVE)
Aim:Induction of hypertrophy of the anticipated liver remnant
to increase functional hepatic reserve.
Indications:< 25 % expected remnant volume in normal liver function
or< 40 % expected remnant volume in compromised liver function.
Contraindications:Significant hypertrophy cannot be expected in liver cirrhosis.
PVE may result in hepatic failure in moderate to severe liver dysfunction.
Abdalla et al. (2001) Br J Surg 88(2): 165-75Broelsch et al. (2004) Surg Clin N Am 84: 495-511
Meta-analysis of PVE *
Complications in less than 5 % of cases.
No specific substance emerged as superior(cyanoacrylate, thrombin, coils or absolute alcohol).
Increase in remnant liver volume averages 12 % of the total liver volume.
Morbidity after consecutive resection less than 15 %.
Mortality after consecutive resection:6-7 % with cirrhosis
0-6,5 % without cirrhosis.
Conclusion:PVE does not increase the risks associated with major liver resection.
* Abdalla et al. (2001) Br J Surg 88(2): 165-75
anticipated small remnant volume, no extrahepatic spread
4 -6 weeks after chemotherapy +expected remnant < 40 % of liver volume
Non-HCC, no transplant option
Child-Pugh Class Abilirubin < 1,9 mg/dl
no portal hypertension
Child-Pugh Class B or C
preoperative PVE (+TACE?)
4-6 weeks
repeat volumetry
expected remnant> 40 % of liver volume
resection
PEI, local ablation,clinical studies,
palliative treatment,TLC
CT oder MRI-volumetry of prospective remnant after virtual resection
Neoadjuvant chemotherapy for primarily unresectable colorectal metastases
No. patients chemotherapy resection rate survival after resectionAdam et al. (2004) * 1104 5-FU + leucovorin 12,5 % 33 % 5y.
+ oxaliplatin / 23 % 10y irinotecanPozzo et al. (2004) ** 40 5-FU + folinic acid 32,5 % > 19 months + irinotecan
Neoadjuvant chemotherapy may render patients with primarilyunresectable colorectal metastases potentially curative resectable.
* Adam et al. (2004) Ann Surg 240(4):644-57** Pozzo et al. (2004) Ann Oncol 15(6):933-9
Neoadjuvant chemotherapy for primarily unresectable HCC
No. patients chemotherapy resection rate survival after resectionLau et al. (2004) * 49 doxorubicin 57 % 98 % 1y
+ cisliplatin 64 % 3y + 5-FU 57 % 5y + interferon-alpha or single doxorubicin
Neoadjuvant chemotherapy may render patients with primarilyunresectable HCC potentially curative resectable.
* Lau et al. (2004) Ann Surg 240(2):299-305
Conclusions
Respect toxic wash-out phase of 4 – 6 weeks prior to liver resection.
Expect potential toxic liver injury.
Consider negative impact of chemotherapy on liver regeneration.
The Child-Pugh Score remains the most widely accepted clinical assessmenttool for preoperative liver function.
Consider portal vein embolization (PVE) in expected liver remnants < 40 %of total liver volume.
Neoadjuvant chemotherapy may render previously unresectable colorectal livermetastases and HCC resectable by downstaging with encouraging results.
The decision to resect and the choice of the extent of a hepatic resectionare largely based on surgical judgement and experience.