limitations in liver resection:

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Limitations in liver resection: Is preoperative chemotherapy limiting the extent of liver resection? Jürgen Klempnauer Department of General, Visceral and Transplantation Surgery Medizinische Hochschule Hannover, Germany

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Limitations in liver resection: Is preoperative chemotherapy limiting the extent of liver resection?. Jürgen Klempnauer Department of General, Visceral and Transplantation Surgery Medizinische Hochschule Hannover, Germany. Typical chemotherapeutic agents - PowerPoint PPT Presentation

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Page 1: Limitations in 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

Page 2: Limitations in liver resection:

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.

Page 3: Limitations in liver resection:

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 *.

Page 4: Limitations in liver resection:

Hepatotoxicity:Common toxicity criteria of the National Cancer Institute, version 2.0

Page 5: Limitations in liver resection:

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.

Page 6: Limitations in liver 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.

Page 7: Limitations in liver resection:

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

Page 8: Limitations in liver resection:

Integration of anatomical and functional imaging modalitiesmay improve properative assessment of hepatic reserve in the future.

Page 9: Limitations in liver resection:
Page 10: Limitations in liver resection:

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.

Page 11: Limitations in liver 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“

Page 12: Limitations in liver resection:

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

Page 13: Limitations in liver resection:

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

Page 14: Limitations in liver resection:

Small for Size Liver Syndrome (SFSS)

Page 15: Limitations in liver resection:

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

Page 16: Limitations in liver resection:

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

Page 17: Limitations in liver resection:

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

Page 18: Limitations in liver 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

Page 19: Limitations in liver resection:

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

Page 20: Limitations in liver resection:

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.