Management Of Liver M E T A S T A S I S Patient Selection

Management of Liver Metastasis: Management of Liver Metastasis: Patient Selection Patient Selection

S K Mathur S K Mathur MS,FACSMS,FACS

Sr Consultant SurgeonSr Consultant SurgeonSurgical GastroenterologySurgical Gastroenterology

HPB Surgery & Liver TransplantationHPB Surgery & Liver Transplantation

•Wockhardt hospitals,Mumbai

Management of Liver Metastasis: Management of Liver Metastasis: Patient SelectionPatient Selection

Hepatic resection of liver metastases:Hepatic resection of liver metastases: remains the preferred therapy for potential cure remains the preferred therapy for potential cure The overall 5-year survival rates : The overall 5-year survival rates : - with R0 resection 35%–58% - with R0 resection 35%–58%

Chemotherapy: Neoadjuvant or AdjuvantChemotherapy: Neoadjuvant or Adjuvant

Local Ablative therapiesLocal Ablative therapies

Use of other adjunctive and adjuvant approaches: Use of other adjunctive and adjuvant approaches: - to expanding the criteria for resectability - to expanding the criteria for resectability of patients with colorectal metastasis of patients with colorectal metastasis


General criteria for fitnessGeneral criteria for fitness

Specific Criteria that decides: Specific Criteria that decides:

the outcome in terms of: the outcome in terms of:

- Risk of recurrence- Risk of recurrence

- Survivals: Disease free and overall- Survivals: Disease free and overall

Anatomical criteria for resectabilityAnatomical criteria for resectability


Specific Criteria:Specific Criteria:

Also depends on nature of Primary tumorAlso depends on nature of Primary tumor

Colorectal malignancyColorectal malignancy

Neuro endocrine tumor (NET)Neuro endocrine tumor (NET)

Non-colorectal / Non NET: Site & typeNon-colorectal / Non NET: Site & type


Selection Criteria- Selection Criteria- Therapy specific:Therapy specific:Resection: - PrimaryResection: - Primary

- re-resection - re-resection AblationAblation

CombinationCombination

Chemotherapy- Neoadjuvan or AdjuvantChemotherapy- Neoadjuvan or Adjuvant


Obviously non resectable:Obviously non resectable: - Extrahepatic disease at multiple sites- Extrahepatic disease at multiple sites - uncontrolled Primary - uncontrolled Primary - Tumor proximity to major hepatic vessels : - Tumor proximity to major hepatic vessels : precluding margin –ve resectionprecluding margin –ve resection

Selection criteria for Resection:Selection criteria for Resection: - Size of liver lesions: <5 cm v/s >5cm- Size of liver lesions: <5 cm v/s >5cm - number of lesions : < 5 v/s >5- number of lesions : < 5 v/s >5 - distribution of lesions: uni v/s bi lobar- distribution of lesions: uni v/s bi lobar - Vol. of residual liver: adequate / <30%- Vol. of residual liver: adequate / <30%

Ann Surg Oncol 2004


Grey zone for resectability:Grey zone for resectability:

Resectable liver met in presence of:Resectable liver met in presence of:

- Extrahepatic disease: - Extrahepatic disease: e.g in colorectal Carcinomae.g in colorectal Carcinoma

-resectable Pulmonary metastasis -resectable Pulmonary metastasis

-hepatic hilar LN-hepatic hilar LN

- R0 resection not possible: - R0 resection not possible:

- resection margin <1cm- resection margin <1cm

- cytoreduction: NET - cytoreduction: NET

- Asymptomatic unknown / uncontrolled primary- Asymptomatic unknown / uncontrolled primary


Other selection criteria for Resection:Other selection criteria for Resection: based on Predictive factors for outcome:based on Predictive factors for outcome: - - time from primary tumor to metastases time from primary tumor to metastases - tumor Grade - tumor Grade - nodal status of primary- nodal status of primary - CEA levels- CEA levels - number of liver lesions- number of liver lesions - size of liver lesions- size of liver lesions - resection margin status- resection margin status

Clinical score for predicting recurrence after hepatic Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of resection for metastatic colorectal cancer: analysis of

1001 consecutive cases. 1001 consecutive cases. Fong Y, Fortner J, Sun RL, et al. Ann Surg. 1999.Fong Y, Fortner J, Sun RL, et al. Ann Surg. 1999.

For the CRS, each of 5 clinical criteria is For the CRS, each of 5 clinical criteria is assigned 1 point:assigned 1 point:

1) node-positive primary1) node-positive primary2)<12 month disease-free interval 2)<12 month disease-free interval 3) >1 liver tumors 3) >1 liver tumors 4) largest tumor >5 cm 4) largest tumor >5 cm 5) CEA >200 ng/mL. 5) CEA >200 ng/mL.

Clinical score for predicting recurrence after hepatic Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of resection for metastatic colorectal cancer: analysis of

1001 consecutive cases. 1001 consecutive cases. Fong Y, Fortner J, Sun RL, et al. Ann Surg. 1999.Fong Y, Fortner J, Sun RL, et al. Ann Surg. 1999.

Analysis of prognostic factors influencing long-term Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic survival after hepatic resection for metastatic

colorectal cancer colorectal cancer

The retrospective analysis of 297 liver The retrospective analysis of 297 liver resections for colorectal metastasesresections for colorectal metastasesThe multivariate analysis showed three independent The multivariate analysis showed three independent negative prognostic factors: negative prognostic factors:

G3 or G4 grade, G3 or G4 grade,

CEA >5 ng/ml, CEA >5 ng/ml,

high MSKCC-CRS: >2 high MSKCC-CRS: >2

CONCLUSIONS: CONCLUSIONS: in the presence of negative prognostic in the presence of negative prognostic factors enrollment of patients in trials exploring new factors enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the adjuvant treatments is suggested to improve the

outcome after surgeryoutcome after surgery..Arru M,et al Italy, World J Surg. 2008,et al Italy, World J Surg. 2008

A Nomogram for Predicting Disease-specific Survival After A Nomogram for Predicting Disease-specific Survival After Hepatic Resection for Metastatic Colorectal Cancer Hepatic Resection for Metastatic Colorectal Cancer

Kattan MW, Gönen M, William R. Jarnagin WR, DeMatteo R, Michael D'Angelica Kattan MW, Gönen M, William R. Jarnagin WR, DeMatteo R, Michael D'Angelica M, Martin Weiser M, Leslie H. Blumgart LS, Fong Y,M, Martin Weiser M, Leslie H. Blumgart LS, Fong Y,

Based on the Cox proportional hazards regression model, a nomogram was constructed (Fig. 2). A version of this nomogram that can be downloaded and installed on a pocket digital assistant (PDA) for routine use can be found at the follow Internet site: www.nomograms.org . It has a bootstrap-corrected concordance index of 0.612 and seems well calibrated

Ann Surg. 2008;247(2):282-287

A Nomogram for Predicting Disease-specific A Nomogram for Predicting Disease-specific Survival After Hepatic Resection for Survival After Hepatic Resection for

Metastatic Colorectal CancerMetastatic Colorectal Cancerpatients with hepatic metastases are not homogeneous patients with hepatic metastases are not homogeneous with respect to risk of recurrence and death, following with respect to risk of recurrence and death, following hepatectomy.hepatectomy.

Individual patient decision making requires better tools Individual patient decision making requires better tools for assessing prognosis to provide patient selection for for assessing prognosis to provide patient selection for surgerysurgery

When refit to those patients used in the original CRSWhen refit to those patients used in the original CRS

the the nomogram predicted more accurately than did the nomogram predicted more accurately than did the Fong scoreFong score when both were applied to the same when both were applied to the same validation dataset.validation dataset.

Ann Surg. 2008;247(2):282-287

Criteria for Resectability of Colorectal Liver Criteria for Resectability of Colorectal Liver MetastasesMetastases

Old Paradigm: Traditional Factors Associated Old Paradigm: Traditional Factors Associated With ResectabilityWith Resectability : :

Tumor NumberTumor Number 3-4 ? 3-4 ?

Tumor SizeTumor Size < /= 3cm ? < /= 3cm ?

Surgical Margin >1 cm?Surgical Margin >1 cm?Microscopic negative margin more important than widthMicroscopic negative margin more important than width

No extrahepatic DiseaseNo extrahepatic Disease??

Earlier reports of 5Yrs Survival: 0 – 20%?Earlier reports of 5Yrs Survival: 0 – 20%?Pawlik, T. M. et al. Oncologist 2008;13:51-64


Copyright ©2008 AlphaMed Press

Pawlik, T. M. et al. Oncologist 2008;13:51-64

Figure 1. Whereas in the past a tumor number greater than four was considered a relative contraindication to hepatic resection, more recent data reveal no survival difference between patients

who had one to three metastases and those who had four or more metastases, all of whom had undergone an R0 (i.e., microscopically negative) resection



Survival following hepatic resection of colorectal metastases is not associated with the width of the negative surgical margin as long as the

margin is completely microscopically negative

Results of R0 Resection for Colorectal Liver Results of R0 Resection for Colorectal Liver Metastases Associated With Extrahepatic DiseaseMetastases Associated With Extrahepatic Disease

Elias D et al ( France) Ann Surg Oncol 2004Elias D et al ( France) Ann Surg Oncol 2004Survival of patients with R0 resectionSurvival of patients with R0 resection

Multivariate Analysis of Prognostic Factorsstatistically significant negative factors in the Cox model : -presence of multiple sites of extrahepatic disease (including peritoneal carcinomatosis; P = .04)

-more than five LMs (P = .02).

Conclusions: EHD in CRC patients with liver metastases should no longer be considered as a contraindication to hepatectomy.


Redefining the resectability of colorectal liver Redefining the resectability of colorectal liver metastasismetastasis::

No more defined by strict criteria on: numbers, size No more defined by strict criteria on: numbers, size and distribution of liver metastasesand distribution of liver metastases

The determination of resectability is now based on:The determination of resectability is now based on:

- whether it is possible to remove all known disease - whether it is possible to remove all known disease

- while leaving behind an adequate functional - while leaving behind an adequate functional

remnant liverremnant liver

Choti MA. Current Colorectal Cancer reports 2008

New paradigm:4New paradigm:4 main Criteria for main Criteria for Resectability of Colorectal Liver MetastasesResectability of Colorectal Liver Metastases

An R0 resection of both the intra- and An R0 resection of both the intra- and extrahepatic disease sites must be feasible. extrahepatic disease sites must be feasible.

At least two adjacent liver segments need to be At least two adjacent liver segments need to be spared. spared.

Vascular inflow and outflow, as well as biliary Vascular inflow and outflow, as well as biliary drainage to the remaining segments, must be drainage to the remaining segments, must be preserved. preserved.

The volume of the liver remaining after The volume of the liver remaining after resection (i.e., the future liver remnant) must be resection (i.e., the future liver remnant) must be adequate adequate


New paradigm:4New paradigm:4 main Criteria for main Criteria for Resectability of Colorectal Liver MetastasesResectability of Colorectal Liver Metastases

The volume of the liver remaining after resection (i.e., the The volume of the liver remaining after resection (i.e., the future liver remnant) must be adequate. future liver remnant) must be adequate.

which usually means at leastwhich usually means at least

20% of the total estimated liver volume for normal 20% of the total estimated liver volume for normal parenchyma:, parenchyma:,

30%–60% if the liver is injured by chemotherapy, 30%–60% if the liver is injured by chemotherapy, steatosis, or hepatitissteatosis, or hepatitis

40%–70% in the presence of cirrhosis, 40%–70% in the presence of cirrhosis, depending on the degree of underlying hepatic dysfunctiondepending on the degree of underlying hepatic dysfunction

[Ferrero A,et al World J Surg 2007; ][Ferrero A,et al World J Surg 2007; ]

Strategies to increase the Resectability Strategies to increase the Resectability

increase/preserve hepatic reserve,increase/preserve hepatic reserve,

- Portal Vein Embolisation: inadequate FLR- Portal Vein Embolisation: inadequate FLR

- Two- stage resection: bilobar disease - Two- stage resection: bilobar disease

combined local therapy: combined local therapy: Resection Plus RFAResection Plus RFA

- Resect- larger lesion- Resect- larger lesion

- Ablate- smaller lesions - Ablate- smaller lesions

decrease tumor size: Chemotherapydecrease tumor size: Chemotherapy

Stratigies to increase the ResectabilityStratigies to increase the Resectability Two- stage heptectomyTwo- stage heptectomy

Indication: unresectable bilobar disease Indication: unresectable bilobar disease due to inadeuate FLRdue to inadeuate FLR

First stage: resect Mets in FLR PVEFirst stage: resect Mets in FLR PVE

22ndnd Stage resection after 3-4weeks Stage resection after 3-4weeks

Results:Results:

-Adam et al. 3-year survival rate of 35% -Adam et al. 3-year survival rate of 35%

-Jaeck et al. 1- and 3-year survival rates of -Jaeck et al. 1- and 3-year survival rates of 70.0% and 54.4% 70.0% and 54.4%

Ann Surg 2000 & Ann Surg 2004

Strategies to increase the Resectability Strategies to increase the Resectability

increase/preserve hepatic reserve,increase/preserve hepatic reserve,

- Portal Vein Embolisation: inadequate FLR - Portal Vein Embolisation: inadequate FLR

- Two- stage resection: bilobar disease - Two- stage resection: bilobar disease

combined local therapy: Resection Plus RFAcombined local therapy: Resection Plus RFA

Decrease tumor size: Decrease tumor size:

- with neo-adjuvant chemotherapy- with neo-adjuvant chemotherapy

Adam et al. reported that rescue surgery Adam et al. reported that rescue surgery for un-resectable colorectal liver for un-resectable colorectal liver metastases downsized by chemotherapy metastases downsized by chemotherapy resulted in a 5-year survival rate of 33% resulted in a 5-year survival rate of 33%

Ann Surg 2004


Contraindication for hepatic resection Contraindication for hepatic resection

Patients with extensive extrahepatic Patients with extensive extrahepatic disease disease

those who progress on systemic those who progress on systemic chemotherapychemotherapy

Management of Liver Metastasis: Management of Liver Metastasis: Patient Selection for re-resectionPatient Selection for re-resection

After "curative" hepatic metastasectomy for colorectal After "curative" hepatic metastasectomy for colorectal cancer, 60% will develop local, regional, or distant cancer, 60% will develop local, regional, or distant recurrence. recurrence. 85% of recurrences occur within the first 30 months of 85% of recurrences occur within the first 30 months of the original resectionthe original resection

30% of recurrences are confined to the liver 30% of recurrences are confined to the liver allowing for consideration of repeat hepatic allowing for consideration of repeat hepatic resections or ablation proceduresresections or ablation procedures repeat resections are associated with a 5-year repeat resections are associated with a 5-year survival rate of 20% to 30%. survival rate of 20% to 30%.

Cancer Control. 2006

Management of Liver Metastasis: Patient Management of Liver Metastasis: Patient Selection in CRC Liver Metastases Selection in CRC Liver Metastases

Chemotherapy: Indications at presentationChemotherapy: Indications at presentationMultiple metastases and stage IV disease Multiple metastases and stage IV disease

Marginally unresectable L M: Marginally unresectable L M: size, number,size, number, or location close to vascular structuresor location close to vascular structures - to down size the metastases- to down size the metastases response could help achieve Ro resectionresponse could help achieve Ro resection

Choti MA. Current Colorectal Cancer reports 2008

Management of Liver Metastasis: Management of Liver Metastasis: Patient Selection for Patient Selection for Local AblationLocal Ablation in in

Colorectal Liver MetastasesColorectal Liver Metastases

Indication for ablation is in patients:Indication for ablation is in patients:

who do not meet the criteria for resectability who do not meet the criteria for resectability

but are candidates for liver-directed therapy but are candidates for liver-directed therapy based upon the presence of liver-only disease. based upon the presence of liver-only disease.

complete margin-negative ablation can be complete margin-negative ablation can be achieved achieved

Predictors of Survival After Radiofrequency Predictors of Survival After Radiofrequency Thermal Ablation of Colorectal Cancer Metastases Thermal Ablation of Colorectal Cancer Metastases

to the Liver: A Prospective Study to the Liver: A Prospective Study

Patients with the dominant lesion less than Patients with the dominant lesion less than 5 cm in diameter had a median survival of 5 cm in diameter had a median survival of 34 months v/s 21 months for lesions 34 months v/s 21 months for lesions greater than 5 cm (greater than 5 cm (PP = .03). = .03).

Survival approached significance for Survival approached significance for patients with <3 tumors versus >3 tumors patients with <3 tumors versus >3 tumors (29 (29 vv 22 months; 22 months; PP = .09). = .09).

Journal of Clinical Oncology, 2005

Management of Liver Metastasis: Management of Liver Metastasis: Patient Selection for LM from NETPatient Selection for LM from NET5 yrs survival: -without resection: 40%5 yrs survival: -without resection: 40%

- after Liver resection: 60% - after Liver resection: 60%

Indications Liver resection:Indications Liver resection:

when Ro resection is possiblewhen Ro resection is possible

Palliative cytoreduction ( 90% of tumor):Palliative cytoreduction ( 90% of tumor):

to improve quality of lifeto improve quality of life - after failure of medical therapy to control - after failure of medical therapy to control

endocrinopathy-related symptomsendocrinopathy-related symptoms

- pain & discomfort due to massive size - pain & discomfort due to massive size

(non-functional tumors)(non-functional tumors) Mayo Clinic. J Am Coll Surg. 2003 Wisconsin Arch Surg. 2006

Treatment of liver metastases from neuroendocrine Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease tumours in relation to the extent of hepatic disease

This study identified LM-specific variables that could be This study identified LM-specific variables that could be used as additional selection criteria for aggressive used as additional selection criteria for aggressive treatment. treatment. From 1992 to 2006, 119 patients underwent staging and From 1992 to 2006, 119 patients underwent staging and treatment of LM. treatment of LM. Three types of LM were identified radiologically:Three types of LM were identified radiologically:

Type I: single metastasis Type I: single metastasis

Type II: isolated metastatic bulk accompanied by smaller Type II: isolated metastatic bulk accompanied by smaller deposits deposits

Type III: disseminated metastatic spread Type III: disseminated metastatic spread Frilling, A.et al; B. J. S., Feb 2009Frilling, A.et al; B. J. S., Feb 2009

Treatment of liver metastases from Treatment of liver metastases from neuroendocrine tumours in relation to the neuroendocrine tumours in relation to the

extent of hepatic disease extent of hepatic disease Results: Results:

Survival rates: 3 yrs 5yrs 10year Survival rates: 3 yrs 5yrs 10year * Entire cohort 76·4% 63·9% 46·5%* Entire cohort 76·4% 63·9% 46·5% There were significant differences in 5- and 10-year There were significant differences in 5- and 10-year

survival between the 3 groupssurvival between the 3 groups * Type I 100% 100%* Type I 100% 100% * Type II 84% 75 %* Type II 84% 75 % * Type III 51% 29 %* Type III 51% 29 %

Conclusion:Conclusion: The localization and biological features of LM from NET The localization and biological features of LM from NET

defines therapeutic management and is predictive of defines therapeutic management and is predictive of survivalsurvival

Frilling, A.et al; B. J. S., Feb 2009Frilling, A.et al; B. J. S., Feb 2009

Management of Liver Metastasis: Management of Liver Metastasis: Patient Selection for LM from NETPatient Selection for LM from NET

NET Liver MetastasisNET Liver Metastasis

Other Prognostic markers•Histological grade of Primary: G1 &G2 v/s G3 &G4 •Site of Primary tumor

M.D. Anderson Cancer Center Journal of Clinical Oncology, 2008:

No Extra hepatic diseaseWorld J Surg Oncol. 2006;

Management of Liver Metastasis:Management of Liver Metastasis: Patient SelectionPatient Selection

Non Colorectal / Non NET Liver MetastasisNon Colorectal / Non NET Liver Metastasis

5 yrs Survival of Liver Resection according 5 yrs Survival of Liver Resection according to Primary:to Primary:

Genitourinary tract: 42 - 60%Genitourinary tract: 42 - 60%

Soft tissue tumors: 30%Soft tissue tumors: 30%

Breast cancer : 41%Breast cancer : 41%

Upper GI : 15-30% Upper GI : 15-30%

Pancreas <15% Pancreas <15%

Adam et al Ann Surg 2006, Harrison et al . Surgery 1997

Hepatic Resection for Noncolorectal Nonendocrine Liver MetsHepatic Resection for Noncolorectal Nonendocrine Liver MetsAnalysis of 1452 Patients and Development of a Prognostic Analysis of 1452 Patients and Development of a Prognostic

Model :Paul Brousse Hospital Villejuif, FranceModel :Paul Brousse Hospital Villejuif, France

In multivariate analysis, factors associated with poor prognosis were: (all P ≤ 0.02).

- patient age >60 years - non-breast origin - melanoma or squamous histology - disease-free interval <12 months - extrahepatic metastases, - R2 resection - major hepatectomy

Adam et al Ann Surg 2006,



A prognostic model based on these factors effectively stratified patients into:

low-risk (0–3 points): 46% 5-year survival

mid-risk (4–6 points): 33% 5-year survival

high-risk (>6 points): <10% 5-year survival groups (P = 0.0001).





Five-Year and Median Survivals for Patients With Five-Year and Median Survivals for Patients With noncolorectal Nonendocrine Liver Metastases From noncolorectal Nonendocrine Liver Metastases From Individual Primary Tumor Sites Grouped by:Individual Primary Tumor Sites Grouped by:

Favorable (Group 1) : > 33%Favorable (Group 1) : > 33%

Intermediate (Group 2): 15 – 30%Intermediate (Group 2): 15 – 30%

Poor Outcomes (Group 3): < 15%Poor Outcomes (Group 3): < 15%




Favourable Prognostic factors for Relapse Favourable Prognostic factors for Relapse Free Survival on multivariate analysis:Free Survival on multivariate analysis:

Primary tumor type: Primary tumor type: metastases from reproductive metastases from reproductive

tract V/s non reproductive tumorstract V/s non reproductive tumors (63% v/s 30%) (63% v/s 30%)

Length of disease free interval from the Length of disease free interval from the primary tumor ( > 24 months).primary tumor ( > 24 months).

Margin status- R0 resections:Margin status- R0 resections:

3 yr survival of 78%.3 yr survival of 78%.

Weitz et al. Ann Surg 2005



presence of extrahepatic disease prior to presence of extrahepatic disease prior to or at the time of hepatectomy or at the time of hepatectomy

Pre hepatectomy disease progression Pre hepatectomy disease progression while on chemotherapywhile on chemotherapy




Tumor type- GISTTumor type- GISTImatinib is the first line treatment.Imatinib is the first line treatment.

Resection to be considered if tumor reach Resection to be considered if tumor reach maximal response to Imatinib or become maximal response to Imatinib or become resistant to it.resistant to it.

Disease free interval of > 24monthsDisease free interval of > 24months

Ro Resection should be possibleRo Resection should be possible

5 yr overall survival rates : 30 -70%5 yr overall survival rates : 30 -70%Antonescu et al,Clin Can Res2005, Antonescu et al,Clin Can Res2005, Demato et al, Ann of Surg Oncology 2002Demato et al, Ann of Surg Oncology 2002Adam et al Ann Surg 2006



Tumor type- MelanomaTumor type- MelanomaOverall survival of patients treated by Overall survival of patients treated by complete resection :28 months.complete resection :28 months.5 yr survival was 29%.5 yr survival was 29%.In patients treated non operatively survival In patients treated non operatively survival was only 6 months.was only 6 months.Extrahepatic disease was not a Extrahepatic disease was not a contraindication for liver resection as long contraindication for liver resection as long as all disease is resectableas all disease is resectable..

Rose et al. Sydney Melanoma unit 2001Rose et al. Sydney Melanoma unit 2001



Tumor type- BreastTumor type- Breast

Solitary Liver metastasesSolitary Liver metastases

Localised (>2) metastases: Localised (>2) metastases:

- resectable by Ro resection- resectable by Ro resection

patients who do not progresspatients who do not progress while on while on systemic chemotherapysystemic chemotherapy

No multiple bone metastasisNo multiple bone metastasis

Elias et al, Am J Surg 2003Elias et al, Am J Surg 2003



Tumor type- BreastTumor type- Breast

Adverse prognostic factors:Adverse prognostic factors:

- Receptor negative status.- Receptor negative status.

- node positive primary.- node positive primary.

- Local recurrence of primary- Local recurrence of primary

- Short disease free survival.- Short disease free survival.

extrahepatic disease is an exclusion extrahepatic disease is an exclusion criteria. criteria.

Elias et al, Am J Surg 2003Elias et al, Am J Surg 2003



Tumor type- Germ cell tumorsTumor type- Germ cell tumorsliver resection for metastatic tumorsliver resection for metastatic tumors

5 yr survival rate : 62%5 yr survival rate : 62%Defined three adverse prognostic factors:Defined three adverse prognostic factors:- Pure embryonal cell carcinoma in the primary - Pure embryonal cell carcinoma in the primary tumor.tumor.- Liver metastasis more than 3 cms. in males- Liver metastasis more than 3 cms. in males- Presence of viable residual disease after - Presence of viable residual disease after

chemotherpy.chemotherpy.

Gholam et al, Cancer 2003Gholam et al, Cancer 2003



ConclusionConclusion

Hepatic resection for metastatic NCNN Hepatic resection for metastatic NCNN tumors is safe and effective in selected tumors is safe and effective in selected patients patients

Primary tumor type Primary tumor type

DFI seem to be the only valid selection DFI seem to be the only valid selection parameters.parameters.

R0 resection must be achievedR0 resection must be achieved

Copyright ©2008 AlphaMed Press


Over the last decade, the criteria for resectability of colorectal liver metastases have been expanded and

have undergone a paradigm shift


Expanding Criteria for Resectability of Colorectal Expanding Criteria for Resectability of Colorectal Liver Metastases Liver Metastases

Timothy M. Pawlik, Richard D. Schulick, Michael A. Choti John HopkinsTimothy M. Pawlik, Richard D. Schulick, Michael A. Choti John Hopkins

Surgical resection is the treatment of choice in patients with colorectal liver metastases, with 5-year survival Surgical resection is the treatment of choice in patients with colorectal liver metastases, with 5-year survival rates reported in the range of 40%–58%. Over the past 10 years, there has been an impetus to expand the rates reported in the range of 40%–58%. Over the past 10 years, there has been an impetus to expand the criteria for defining resectability for patients with colorectal metastases.criteria for defining resectability for patients with colorectal metastases. In the past, such features as the number of metastases (three to four), the size of the tumor lesion, and a In the past, such features as the number of metastases (three to four), the size of the tumor lesion, and a mandatory 1-cm margin of resection dictated who was "resectable.“mandatory 1-cm margin of resection dictated who was "resectable.“ More recently, the criteria for resectability have been expanded to include any patient in whom all disease can More recently, the criteria for resectability have been expanded to include any patient in whom all disease can be removed with a negative margin and who has adequate hepatic volume/reserve.be removed with a negative margin and who has adequate hepatic volume/reserve. Specifically, instead of resectability being defined by what is removed, decisions concerning resectability now Specifically, instead of resectability being defined by what is removed, decisions concerning resectability now center around what will remain after resection.center around what will remain after resection.Under this new paradigm, the number of patients with resectable disease can be expanded by Under this new paradigm, the number of patients with resectable disease can be expanded by increasing/preserving hepatic reserve (e.g., portal vein embolization, two-stage hepatectomy), combining increasing/preserving hepatic reserve (e.g., portal vein embolization, two-stage hepatectomy), combining resection with ablation, and decreasing tumor size (preoperative chemotherapy). resection with ablation, and decreasing tumor size (preoperative chemotherapy). The criteria for resectability have also expanded to include patients with extrahepatic disease. Rather than The criteria for resectability have also expanded to include patients with extrahepatic disease. Rather than being an absolute contraindication to surgery, patients with both intra- and extrahepatic disease should being an absolute contraindication to surgery, patients with both intra- and extrahepatic disease should potentially be considered for resection based on strict selection criteria. potentially be considered for resection based on strict selection criteria.

The expansion of criteria for resectability of colorectal liver The expansion of criteria for resectability of colorectal liver metastases requires a much more nuanced and sophisticated metastases requires a much more nuanced and sophisticated approach to the patient with advanced disease. approach to the patient with advanced disease. A therapeutic approach that includes all aspects of A therapeutic approach that includes all aspects of multidisciplinary and multimodality care is required to select and multidisciplinary and multimodality care is required to select and treat this complex group of patients.treat this complex group of patients.

The Oncologist, 2008;The Oncologist, 2008;


It involves: a) multi disciplinary approach It involves: a) multi disciplinary approach and b) a correct preoperative planningand b) a correct preoperative planningTo convert unresectable disease into To convert unresectable disease into

resectable.resectable. downsizing the tumor with pre op therapydownsizing the tumor with pre op therapy Increasing remnant liver Volume:Increasing remnant liver Volume:

- by doing staged resection- by doing staged resection - pre-op Portal vein embolisation- pre-op Portal vein embolisation

Combining ablative therapy with resectionCombining ablative therapy with resection

Management of Liver Metastasis: Management of Liver Metastasis: Patient Selection: Patient Selection: ConclusionsConclusions

Patient selection for management of liver Patient selection for management of liver metastases is going to be “Dynamic Process”metastases is going to be “Dynamic Process”

The criteria for resection will get expanded as The criteria for resection will get expanded as long as Ro resection can be achievedlong as Ro resection can be achieved

A rational use of “Multi A rational use of “Multi disciplinary approach”disciplinary approach”

is important to select a patient for various is important to select a patient for various available therapeutic modalities to be used available therapeutic modalities to be used in a appropriate sequential order with a in a appropriate sequential order with a aim to achieve Ro resection aim to achieve Ro resection

THANK YOUTHANK YOU

Combination of surgery and chemotherapy and the role of Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panelliver metastases: recommendations from an expert panelon behalf of the European Colorectal Metastases Treatment Group on behalf of the European Colorectal Metastases Treatment Group

Ann. Onc., January 19, 2009; (2009)Ann. Onc., January 19, 2009; (2009) The past 5 years have seen the clear recognition that the administration of The past 5 years have seen the clear recognition that the administration of chemotherapy to patients with initially unresectable colorectal liver chemotherapy to patients with initially unresectable colorectal liver metastases can increase the number of patients who can undergo metastases can increase the number of patients who can undergo potentially curative secondary liver resection. Coupled with this, recent data potentially curative secondary liver resection. Coupled with this, recent data have emerged that show that perioperative chemotherapy confers a have emerged that show that perioperative chemotherapy confers a disease-free survival advantage over surgery alone in colorectal cancer disease-free survival advantage over surgery alone in colorectal cancer (CRC) patients with initially resectable liver disease. The purpose of this (CRC) patients with initially resectable liver disease. The purpose of this paper is to build on the existing knowledge and review the issues paper is to build on the existing knowledge and review the issues surrounding the use of chemotherapy ± targeted agents combined with surrounding the use of chemotherapy ± targeted agents combined with surgery in the treatment of CRC patients with liver metastases, with a view surgery in the treatment of CRC patients with liver metastases, with a view to providing clinical recommendations. An international panel of 21 experts to providing clinical recommendations. An international panel of 21 experts in colorectal oncology comprising liver surgeons and medical oncologists in colorectal oncology comprising liver surgeons and medical oncologists reviewed the available evidence. In a major change to clinical practice,reviewed the available evidence. In a major change to clinical practice,

the panel's recommendation was that the majority of the panel's recommendation was that the majority of patients with CRC liver metastases should be treated up patients with CRC liver metastases should be treated up front with chemotherapy, irrespective of the initial front with chemotherapy, irrespective of the initial resectability status of their metastases. resectability status of their metastases.



Disease free survival is an effective Disease free survival is an effective surrogate for favorable tumor biology.surrogate for favorable tumor biology.Primary tumor type is a important Primary tumor type is a important prognostic marker.prognostic marker.Behavior of the hepatic metastasis is Behavior of the hepatic metastasis is similar to the primary tumor similar to the primary tumor venous invasion by the primary or venous invasion by the primary or positive nodal status predict adverse positive nodal status predict adverse prognostic factors after hepatectomy.prognostic factors after hepatectomy.



Hepatic metastases : - solitary in 56% - unilateral in 71% (mean diameter, 5.5cm) - Extrahepatic metastases were present in 22%.

The most common primary sites were: - breast 32% - gastrointestinal 16% - urologic 14%

The most common histologies : - adenocarcinoma 60% - GIST/sarcoma 13.5% - melanoma 13%

R0 resection was achieved in 83% of patients

Overall and disease-free survivals at 5 years were 36% and 21% and at 10 years were 23% and 15%, respectively.


Proposal of criteria to select candidates with colorectal liver Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring metastases for hepatic resection: comparison of our scoring

system to the positive number of risk factors.system to the positive number of risk factors.Nagashima I, Takada T, Adachi M, Nagawa H, Muto T, Okinaga K.Nagashima I, Takada T, Adachi M, Nagawa H, Muto T, Okinaga K.

Multivariate analysis showed significant and independent Multivariate analysis showed significant and independent prognostic factors for poor survival after hepatectomy (P prognostic factors for poor survival after hepatectomy (P < 0.05). :< 0.05). :

- multiple tumors- multiple tumors - largest tumor greater than 5 cm in diameter - largest tumor greater than 5 cm in diameter - unresectable extrahepatic metastases - unresectable extrahepatic metastases

3 more factors were selected by a stepwise method of 3 more factors were selected by a stepwise method of Cox regression analysis ( P < 0.20). Cox regression analysis ( P < 0.20).

- serosa invasion, - serosa invasion, - local lymph node metastases of primary cancers,- local lymph node metastases of primary cancers, - and post-operative disease free interval less than 1 - and post-operative disease free interval less than 1

year including synchronous hepatic metastasisyear including synchronous hepatic metastasis

World J Gastroenterol. 2006

Proposal of criteria to select candidates with Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive comparison of our scoring system to the positive

number of risk factors.number of risk factors.Nagashima I, Takada T, Adachi M, Nagawa H, Muto T, Okinaga K.Nagashima I, Takada T, Adachi M, Nagawa H, Muto T, Okinaga K.

Using these six variables:Using these six variables: created a new scoring formula to classify created a new scoring formula to classify patients with colorectal liver metastases. patients with colorectal liver metastases.

CONCLUSION:CONCLUSION: Both, new scoring system and the positive Both, new scoring system and the positive

number of significant prognostic factors number of significant prognostic factors are are useful to classify patients with colorectal liver useful to classify patients with colorectal liver metastases in the preoperative selection of good metastases in the preoperative selection of good candidates for hepatic resection.candidates for hepatic resection.



Elias D et al ( France) Ann Surg Oncol 2004Elias D et al ( France) Ann Surg Oncol 2004

From January 1987 to January 2001, 75 patients From January 1987 to January 2001, 75 patients underwent a complete R0 resection of extrahepatic underwent a complete R0 resection of extrahepatic disease simultaneously with hepatectomy for colorectal disease simultaneously with hepatectomy for colorectal liver metastases. liver metastases.

Compared the survival rates: with that of the Compared the survival rates: with that of the patients without extrahepatic disease (n = 219) patients without extrahepatic disease (n = 219) who underwent an R0 hepatectomy for who underwent an R0 hepatectomy for colorectal LM in the same institution during the colorectal LM in the same institution during the same time periodsame time period Analysed prognostic factors for poor outcomeAnalysed prognostic factors for poor outcome

Expanding Criteria for Resectability of Colorectal Expanding Criteria for Resectability of Colorectal Liver Metastases Liver Metastases

Timothy M. Pawlik, Richard D. Schulick, Michael A. Choti John Hopkins Timothy M. Pawlik, Richard D. Schulick, Michael A. Choti John Hopkins

The Oncologist, 2008;The Oncologist, 2008; Surgical resection is the treatment of choice in patients with colorectal liver metastases, with 5-Surgical resection is the treatment of choice in patients with colorectal liver metastases, with 5-year survival rates reported in the range of 40%–58%. Over the past 10 years, there has been year survival rates reported in the range of 40%–58%. Over the past 10 years, there has been an impetus to expand the criteria for defining resectability for patients with colorectal an impetus to expand the criteria for defining resectability for patients with colorectal metastases.metastases. In the past, such features as the number of metastases (three to four), the size of the tumor In the past, such features as the number of metastases (three to four), the size of the tumor lesion, and a mandatory 1-cm margin of resection dictated who was "resectable.“lesion, and a mandatory 1-cm margin of resection dictated who was "resectable.“ More recently, the criteria for resectability have been expanded to include any patient in whom More recently, the criteria for resectability have been expanded to include any patient in whom all disease can be removed with a negative margin and who has adequate hepatic all disease can be removed with a negative margin and who has adequate hepatic volume/reserve.volume/reserve. Specifically, instead of resectability being defined by what is removed, decisions concerning Specifically, instead of resectability being defined by what is removed, decisions concerning resectability now center around what will remain after resection.resectability now center around what will remain after resection.

Under this new paradigm, the number of patients with resectable disease can be expanded by Under this new paradigm, the number of patients with resectable disease can be expanded by increasing/preserving hepatic reserve (e.g., portal vein embolization, two-stage hepatectomy), increasing/preserving hepatic reserve (e.g., portal vein embolization, two-stage hepatectomy), combining resection with ablation, and decreasing tumor size (preoperative chemotherapy). combining resection with ablation, and decreasing tumor size (preoperative chemotherapy). The criteria for resectability have also expanded to include patients with extrahepatic disease. The criteria for resectability have also expanded to include patients with extrahepatic disease. Rather than being an absolute contraindication to surgery, patients with both intra- and Rather than being an absolute contraindication to surgery, patients with both intra- and extrahepatic disease should potentially be considered for resection based on strict selection extrahepatic disease should potentially be considered for resection based on strict selection criteria. The expansion of criteria for resectability of colorectal liver metastases requires a much criteria. The expansion of criteria for resectability of colorectal liver metastases requires a much more nuanced and sophisticated approach to the patient with advanced disease. A therapeutic more nuanced and sophisticated approach to the patient with advanced disease. A therapeutic approach that includes all aspects of multidisciplinary and multimodality care is required to approach that includes all aspects of multidisciplinary and multimodality care is required to select and treat this complex group of patients. select and treat this complex group of patients.

Neuroendocrine hepatic metastases: does aggressive Neuroendocrine hepatic metastases: does aggressive management improve survival management improve survival

Touzios JGTouzios JG, , Kiely JMKiely JM, , Pitt SCPitt SC, , Rilling WSRilling WS, , Quebbeman EJQuebbeman EJ, , Wilson SDWilson SD, , Pitt Pitt HAHA. Wisconsin Ann Surg. 2005 . Wisconsin Ann Surg. 2005

hepatic metastases from NET :N =60 hepatic metastases from NET :N =60 23 received no aggressive treatment of their liver metastases, 23 received no aggressive treatment of their liver metastases, 19 were treated with hepatic resection and/or ablation, 19 were treated with hepatic resection and/or ablation, 18 were managed with TACE 18 were managed with TACE RESULTS: RESULTS:

Survival Median and 5-yearSurvival Median and 5-year * Nonaggressive group 20 months 25% * Nonaggressive group 20 months 25% * Resection/Ablation group >96 months 72% (P < 0.05) * Resection/Ablation group >96 months 72% (P < 0.05) * TACE group 50 months 50% * TACE group 50 months 50% Patients with more than 50% liver involvement had a poor outcome (P Patients with more than 50% liver involvement had a poor outcome (P

< 0.001). < 0.001). CONCLUSIONS: CONCLUSIONS: -Aggressive management of NET hepatic metastases does improve -Aggressive management of NET hepatic metastases does improve

survival, survival, -TACE increases the patient population eligible for this strategy, -TACE increases the patient population eligible for this strategy,




THANK YOU..!THANK YOU..!



R0 resection must be achieved.R0 resection must be achieved.

Comparison with colorectal Comparison with colorectal metastasismetastasis

Reasons for success of liver resection in Reasons for success of liver resection in colorectal metastasis : two conceptscolorectal metastasis : two concepts

- favourable tumor biology, inefficient - favourable tumor biology, inefficient dissemination into blood stream, and dissemination into blood stream, and inefficient adhesion molecules.inefficient adhesion molecules.

- tumor spread by portal vein leads to - tumor spread by portal vein leads to effective entrapment by the liver, leading effective entrapment by the liver, leading to less common extrahepatic disease.to less common extrahepatic disease.

COLORECTAL AND COLORECTAL AND NEUROENDOCRINENEUROENDOCRINE

Hepatic resection is a well established Hepatic resection is a well established modality.modality.

Colorectal 3 yr survival rates 30% to 61% Colorectal 3 yr survival rates 30% to 61% and 5 yr survival rates 16% to 51%. and 5 yr survival rates 16% to 51%.

( Fong et al, 1997, Scheele et al,1995)( Fong et al, 1997, Scheele et al,1995)

Neuroendocrine tumors 5 yr survival of Neuroendocrine tumors 5 yr survival of 76% with surgical resections. 76% with surgical resections.

( Chamberlain et al 2000)( Chamberlain et al 2000)

The factors governing the outcomes are The factors governing the outcomes are fairly well demarcated.fairly well demarcated.

Issues in NCNNIssues in NCNN

Smaller number of series.Smaller number of series.

Inclusion of multiple tumor types in the Inclusion of multiple tumor types in the same series to have a large number of same series to have a large number of patients to analyze. patients to analyze.

Series summarizing multiple Series summarizing multiple tumor typestumor types

Goering et.al.Am J of Surg 183: 384-Goering et.al.Am J of Surg 183: 384-389, 2002389, 2002

48 patients with liver resection or 48 patients with liver resection or ablative therapy.ablative therapy.

5 yr survival rate of 39%.5 yr survival rate of 39%.

3 yr survival- Geniourinary- 52%, Soft 3 yr survival- Geniourinary- 52%, Soft tissue tumors- 34% vs neuroendocine tissue tumors- 34% vs neuroendocine 91%. 91%.


Elias et al, Am.Coll of Surg. 187: 493, Elias et al, Am.Coll of Surg. 187: 493, 1998.1998.

147 patients with mets from non 147 patients with mets from non colorectal primary.colorectal primary.

Operative mortality of 2%.Operative mortality of 2%.

5 yr survival rates: Breast 20%, Testicular 5 yr survival rates: Breast 20%, Testicular 46%, Sarcoma 18%, Gastric 20%.46%, Sarcoma 18%, Gastric 20%.


Laurent et al. World J Surg:25:1532-1536 , Laurent et al. World J Surg:25:1532-1536 , 2001.2001.

39 patients.39 patients.

5 year survival for the entire group was 35%.5 year survival for the entire group was 35%.

However they noted that 5 yr survival was However they noted that 5 yr survival was 100% for patients with disease free interval of 100% for patients with disease free interval of 24 months or more vs. 10% for patients with 24 months or more vs. 10% for patients with disease free interval of less than 24 monthsdisease free interval of less than 24 months

The MSKCC ExperienceThe MSKCC Experience

Weitz et al 2004.Weitz et al 2004.

Patients from 1981 t0 2002.Patients from 1981 t0 2002.

141 patients141 patients

33% had postoperative complications but 33% had postoperative complications but 30 day mortality was 0.30 day mortality was 0.

3 yr relapse free survival 30%.3 yr relapse free survival 30%.

Prognostic factors:Prognostic factors:

Primary tumor type.Primary tumor type.

Length of disease free interval from the Length of disease free interval from the primary tumor ( > 24 months).primary tumor ( > 24 months).

Margin status- R0 resections had 3 yr Margin status- R0 resections had 3 yr survival of 78%.survival of 78%.

R 0 resection and survivalR 0 resection and survival

Disease free interval and Disease free interval and survivalsurvival

Series focusing on one tumor Series focusing on one tumor type- type- SARCOMASSARCOMAS

Demato et al, 2002 Ann of Surg Demato et al, 2002 Ann of Surg Oncology 9: 831-839.Oncology 9: 831-839.

56 patients admitted at MSKCC.56 patients admitted at MSKCC.

GIST and stromal tumors were the most GIST and stromal tumors were the most common types.common types.

5 yr overall survival rates were 30%5 yr overall survival rates were 30%

Disease free interval of less than 24 Disease free interval of less than 24 months was adverse prognostic factor.months was adverse prognostic factor.

At present Imatinib is the first line treatment.At present Imatinib is the first line treatment.Resection to be considered if tumor reach Resection to be considered if tumor reach maximal response to Imatinib or become maximal response to Imatinib or become resistant to it.resistant to it.Resection improves survival only if all tumor can Resection improves survival only if all tumor can be removed.be removed.

( Antonescu et al 2005,Clin Can Res 11: 4812- ( Antonescu et al 2005,Clin Can Res 11: 4812- 4910.)4910.)

Resection Vs. other treatment Resection Vs. other treatment for sarcomasfor sarcomas

DFI and survival for sarcomasDFI and survival for sarcomas

MelanomasMelanomas

Hepatic mets are diagnosed in 10 to 20% Hepatic mets are diagnosed in 10 to 20% of cases of Stage 4 melanomas.of cases of Stage 4 melanomas.Rose et al Sydney Melanoma unit 2001.Rose et al Sydney Melanoma unit 2001.26204 patients of melanoma.26204 patients of melanoma.1750 patients had liver mets ( 6.7%)1750 patients had liver mets ( 6.7%)34 underwent an exploration out of which 34 underwent an exploration out of which only 24 had resection.only 24 had resection.Out of the 10 non resected patients the Out of the 10 non resected patients the mean survival was only 4.4 months.mean survival was only 4.4 months.

Overall survival of patients treated by Overall survival of patients treated by complete resection was 28 months.complete resection was 28 months.

5 yr survival was 29%.5 yr survival was 29%.

In patients treated non operatively In patients treated non operatively survival was only 6 months.survival was only 6 months.

Extrahepatic disease was not a Extrahepatic disease was not a contraindication for liver resection as contraindication for liver resection as long as all disease is resectable.long as all disease is resectable.



Prognostic factorsPrognostic factors

Weitz et al. Ann Surg 2005

Although no Level 1 evidence exists that Although no Level 1 evidence exists that liver resection in metastatic Ca Breast liver resection in metastatic Ca Breast improves survival, more and more improves survival, more and more recently published series show 5 yr recently published series show 5 yr survival rates of 34% to 61%.survival rates of 34% to 61%.

Elias et al, Am J Surg 2003 185:158-Elias et al, Am J Surg 2003 185:158-164.164.

Vlastos et al, 2004, Ann of Surg Onco. Vlastos et al, 2004, Ann of Surg Onco. 11 :869-874.11 :869-874.

BreastBreast

This is when compared to patients of liver This is when compared to patients of liver metastasis who receive only metastasis who receive only chemotherapy --- rarely if ever survive for chemotherapy --- rarely if ever survive for more than 5 years.more than 5 years.

Ablation in Breast metastasesAblation in Breast metastases

More study is required within the era of the latest More study is required within the era of the latest systemic therapies but systemic therapies but

Ablation compares well with the surgical Ablation compares well with the surgical literatureliterature– Median 32 monthsMedian 32 months– 5-yr survival of 37% in selected patients5-yr survival of 37% in selected patients

And can be readily combined with systemic And can be readily combined with systemic therapytherapy

Adverse prognostic factors:Adverse prognostic factors:

- Receptor negative status.- Receptor negative status.

- node positive primary.- node positive primary.

- Local recurrence of primary- Local recurrence of primary

- Short disease free survival.- Short disease free survival.

In most of the series extrahepatic In most of the series extrahepatic disease is an exclusion criteria. disease is an exclusion criteria.

Specific Features of Breast Specific Features of Breast MetastasesMetastases

It is not uncommon for the background liver It is not uncommon for the background liver parenchyma to be scarred and fibrotic post parenchyma to be scarred and fibrotic post chemotherapy.chemotherapy.

Tumours may be harder to image/target. Tumours may be harder to image/target.

More likely to get infiltrative lesionsMore likely to get infiltrative lesions

This is reflected in positive resection margin This is reflected in positive resection margin rates post liver resection 35% (Adam 2006)rates post liver resection 35% (Adam 2006)

Development of multiple new tumours in a Development of multiple new tumours in a short-time frame.short-time frame.

Some authors suggest that patients should Some authors suggest that patients should first receive systemic chemotherapy and first receive systemic chemotherapy and patients who do not progresspatients who do not progress only should only should be taken up for liver resection.be taken up for liver resection.

Valid criteria for patient selection cannot Valid criteria for patient selection cannot be defined at this time.be defined at this time.

Gastric and Pancreatic cancerGastric and Pancreatic cancer

Ochiai et al 1994, Br. J Surg 81:1175-Ochiai et al 1994, Br. J Surg 81:1175-1178.1178.

6540 patients of gastric cancer, only 30 6540 patients of gastric cancer, only 30 (0.46%) underwent resection for liver (0.46%) underwent resection for liver mets.mets.

3 yr survival 20% and no 5 yr survivors.3 yr survival 20% and no 5 yr survivors.

Pancreatic cancer: Detry et al, 2003Pancreatic cancer: Detry et al, 2003

No 3 yr survivors.No 3 yr survivors.

Liver resection cannot be recommended Liver resection cannot be recommended for these patients.for these patients.

10% of patients with renal tumors will 10% of patients with renal tumors will develop Liver metastasis.develop Liver metastasis.Less than 10% will survive for more than 1 Less than 10% will survive for more than 1 yr.yr.Alves et al, 2003. Ann of Surg Onco Alves et al, 2003. Ann of Surg Onco 10:705-710.10:705-710.Median survival was 26 months with 3 yr Median survival was 26 months with 3 yr survival of 26%.survival of 26%.

DFI of less than 24 months and metastasis DFI of less than 24 months and metastasis diameter of more than 5 cm were adverse diameter of more than 5 cm were adverse prognostic factors.prognostic factors.

Liver resection seems justified in patients Liver resection seems justified in patients where a complete resection is possible.where a complete resection is possible.

Specific Features of Breast Specific Features of Breast MetastasesMetastases

It is not uncommon for the background liver It is not uncommon for the background liver parenchyma to be scarred and fibrotic post parenchyma to be scarred and fibrotic post chemotherapy.chemotherapy.

Tumours may be harder to image/target. Tumours may be harder to image/target.

More likely to get infiltrative lesionsMore likely to get infiltrative lesions

This is reflected in positive resection margin This is reflected in positive resection margin rates post liver resection 35% (Adam 2006)rates post liver resection 35% (Adam 2006)

Development of multiple new tumours in a Development of multiple new tumours in a short-time frame.short-time frame.

Germ cell tumorsGerm cell tumors

Gholam et al Cancer 2003. 98:745-752.Gholam et al Cancer 2003. 98:745-752.

37 patients who had undergone liver 37 patients who had undergone liver resection for metastatic tumors. resection for metastatic tumors.

All patients had developed Cisplatin based All patients had developed Cisplatin based chemotherapy.chemotherapy.

5 yr survival rate was 62%.5 yr survival rate was 62%.

Defined three adverse prognostic factors:Defined three adverse prognostic factors:

- Pure embryonal cell carcinoma in the - Pure embryonal cell carcinoma in the primary tumor.primary tumor.

- Liver metastasis more than 3 cms.- Liver metastasis more than 3 cms.

- Presence of viable residual disease after - Presence of viable residual disease after chemotherpy.chemotherpy.

Male patients with liver tumors greater Male patients with liver tumors greater than 3 cms represented high risk group than 3 cms represented high risk group that may not benefit from liver resection.that may not benefit from liver resection.

– Analysis of prognostic factors influencing long-term survival after hepatic resection Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic colorectal cancer.for metastatic colorectal cancer.

– ArruArru M M, , AldrighettiAldrighetti L L, , CastoldiCastoldi R R, , DiDi Palo S Palo S, , OrsenigoOrsenigo E E, , Stella MStella M, , PulitanòPulitanò C C, , GavazziGavazzi F F, , FerlaFerla G G, , DiDi Carlo V Carlo V, , StaudacherStaudacher C C..

– Department of Surgery, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Department of Surgery, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. Italy. [email protected]@hsr.it World J Surg. 2008 Jan;32(1):93-103 World J Surg. 2008 Jan;32(1):93-103

– BACKGROUND: The aim of this study was to analyze the prognostic factors associated with BACKGROUND: The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. METHODS: The variables included 297 liver resections for colorectal metastases. METHODS: The variables considered included disease stage, differentiation grade, site and nodal metastasis of the considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). RESULTS: The univariate analysis revealed a significant difference (p < 0.05) in CRS). RESULTS: The univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2. The multivariate analysis showed three independent negative months, MSKCC-CRS >2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS. prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS. CONCLUSIONS: No single prognostic factor proved to be associated with a sufficiently CONCLUSIONS: No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3-G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-some prognostic factors (G3-G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.improve the outcome after surgery.

Analysis of prognostic factors influencing long-term Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic survival after hepatic resection for metastatic

colorectal cancer colorectal cancer The retrospective analysis n=297 liver resections for The retrospective analysis n=297 liver resections for

colorectal metastases.colorectal metastases.

METHODS: The variables considered included METHODS: The variables considered included disease stage, differentiation grade, site and disease stage, differentiation grade, site and nodal metastasis of the primary tumor, nodal metastasis of the primary tumor, number and diameter of the lesions, time from number and diameter of the lesions, time from primary cancer to metastasis, preoperative CEA primary cancer to metastasis, preoperative CEA level, adjuvant chemotherapy, type of resection, level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal intraoperative ultrasonography and portal clamping use, blood loss, transfusions, clamping use, blood loss, transfusions, complications, hospitalization, surgical margins complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). status, and a clinical risk score (MSKCC-CRS).

Arru M,et al Italy, World J Surg. 2008,et al Italy, World J Surg. 2008


Elias D et al ( France) Ann Surg Oncol 2004Elias D et al ( France) Ann Surg Oncol 2004

After a median follow-up of 4.9 years After a median follow-up of 4.9 years (range, 1.7–13.4 years):(range, 1.7–13.4 years): the 3- and 5-year overall survival rates the 3- and 5-year overall survival rates were 45% and 28%, respectively among were 45% and 28%, respectively among the patients with extrahepatic disease the patients with extrahepatic disease compared with 56% and 33%, for patients compared with 56% and 33%, for patients without EHD (without EHD (PP = .15) = .15) negative prognostic factors for surgery: negative prognostic factors for surgery:

-presence of multiple EHD sites -presence of multiple EHD sites - more than five liver metastases - more than five liver metastases

A Nomogram for Predicting Disease-specific A Nomogram for Predicting Disease-specific Survival After Hepatic Resection for Survival After Hepatic Resection for

Metastatic Colorectal CancerMetastatic Colorectal CancerPosted 03/14/2008Posted 03/14/2008Michael W. Kattan, PhD; Mithat Gönen, PhD; William R. Jarnagin, MD, PhD; Ronald DeMatteo, Michael W. Kattan, PhD; Mithat Gönen, PhD; William R. Jarnagin, MD, PhD; Ronald DeMatteo, MD; Michael D'Angelica, MD; Martin Weiser, MD; Leslie H. Blumgart, MD; Yuman Fong, MDMD; Michael D'Angelica, MD; Martin Weiser, MD; Leslie H. Blumgart, MD; Yuman Fong, MDAuthor InformationAuthor InformationAbstract and IntroductionAbstract and IntroductionAbstractAbstractPurpose:Purpose: To develop a tool for predicting survival after liver resection for patients with stage IV To develop a tool for predicting survival after liver resection for patients with stage IV colorectal cancer. By using a nomogram we are trying to improve on the current practice of using colorectal cancer. By using a nomogram we are trying to improve on the current practice of using prognostic scores for evaluating risks of therapeutic failure.prognostic scores for evaluating risks of therapeutic failure.Patients and Methods:Patients and Methods: All patients admitted to Memorial Sloan-Kettering Cancer Center All patients admitted to Memorial Sloan-Kettering Cancer Center (MSKCC) for curative intent for treatment of metastatic disease from colorectal cancer between (MSKCC) for curative intent for treatment of metastatic disease from colorectal cancer between January 1986 and December 1999 were included,( n=1477) . A nomogram was developed as a January 1986 and December 1999 were included,( n=1477) . A nomogram was developed as a graphical representation of a Cox proportional hazards regression model. The nomogram was graphical representation of a Cox proportional hazards regression model. The nomogram was verified for discrimination and calibration, both employing bootstrapping to obtain relatively verified for discrimination and calibration, both employing bootstrapping to obtain relatively unbiased estimates.unbiased estimates.Results:Results: Using nodal status of the primary tumor, disease-free interval, size of the largest Using nodal status of the primary tumor, disease-free interval, size of the largest metastatic tumor, preoperative carcinoembryonic antigen, bilateral resection, extensive resection metastatic tumor, preoperative carcinoembryonic antigen, bilateral resection, extensive resection (lobectomy or more), gender, number of hepatic tumors, primary cancer site (colon vs. rectum), (lobectomy or more), gender, number of hepatic tumors, primary cancer site (colon vs. rectum), and age, the nomogram achieved a concordance index of 0.61, statistically significantly greater and age, the nomogram achieved a concordance index of 0.61, statistically significantly greater than chance. The nomogram also had very good calibration.than chance. The nomogram also had very good calibration.Conclusion:Conclusion: This nomogram is a predictive tool, upon external validation, that can routinely be This nomogram is a predictive tool, upon external validation, that can routinely be used to counsel patients in making treatment decisions. The discriminatory ability of the used to counsel patients in making treatment decisions. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to nomogram indicates that this population should not be considered homogeneous with respect to risk of death.risk of death.

Ann Surg. 2008;247(2):282-287

Tables for:Tables for:A Nomogram for Predicting Disease-specific Survival After A Nomogram for Predicting Disease-specific Survival After

Hepatic Resection for Metastatic Colorectal CancerHepatic Resection for Metastatic Colorectal Cancer[Ann Surg. 2008;247(2):282-287.[Ann Surg. 2008;247(2):282-287.

Proposal of criteria to select candidates with colorectal liver metastases Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive for hepatic resection: comparison of our scoring system to the positive

number of risk factors.number of risk factors.NagashimaNagashima I I, , Takada TTakada T, , Adachi MAdachi M, , NagawaNagawa H H, , Muto TMuto T, , OkinagaOkinaga K K..

– Department of Surgery, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Department of Surgery, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan. [email protected] ac.jpTokyo 173-8605, Japan. [email protected] ac.jp

– AIM: To select accurately good candidates of hepatic resection for colorectal liver AIM: To select accurately good candidates of hepatic resection for colorectal liver metastasis. METHODS: Thirteen clinicopathological features, which were recognized only metastasis. METHODS: Thirteen clinicopathological features, which were recognized only before or during surgery, were selected retrospectively in 81 consecutive patients in one before or during surgery, were selected retrospectively in 81 consecutive patients in one hospital (Group I). These features were entered into a multivariate analysis to determine hospital (Group I). These features were entered into a multivariate analysis to determine independent and significant variables affecting long-term prognosis after hepatectomy. independent and significant variables affecting long-term prognosis after hepatectomy. Using selected variables, we created a scoring formula to classify patients with colorectal Using selected variables, we created a scoring formula to classify patients with colorectal liver metastases to select good candidates for hepatic resection. The usefulness of the new liver metastases to select good candidates for hepatic resection. The usefulness of the new scoring system was examined in a series of 92 patients from another hospital (Group II), scoring system was examined in a series of 92 patients from another hospital (Group II), comparing the number of selected variables. RESULTS: Among 81 patients of Group I, comparing the number of selected variables. RESULTS: Among 81 patients of Group I, multivariate analysis, i.e. Cox regression analysis, showed that multiple tumors, the largest multivariate analysis, i.e. Cox regression analysis, showed that multiple tumors, the largest tumor greater than 5 cm in diameter, and resectable extrahepatic metastases were tumor greater than 5 cm in diameter, and resectable extrahepatic metastases were significant and independent prognostic factors for poor survival after hepatectomy (P < significant and independent prognostic factors for poor survival after hepatectomy (P < 0.05). In addition, these three factors: serosa invasion, local lymph node metastases of 0.05). In addition, these three factors: serosa invasion, local lymph node metastases of primary cancers, and post-operative disease free interval less than 1 year including primary cancers, and post-operative disease free interval less than 1 year including synchronous hepatic metastasis, were not significant, however, they were selected by a synchronous hepatic metastasis, were not significant, however, they were selected by a stepwise method of Cox regression analysis (0.05 < P < 0.20). Using these six variables, we stepwise method of Cox regression analysis (0.05 < P < 0.20). Using these six variables, we created a new scoring formula to classify patients with colorectal liver metastases. Finally, created a new scoring formula to classify patients with colorectal liver metastases. Finally, our new scoring system not only classified patients in Group I very well, but also that in our new scoring system not only classified patients in Group I very well, but also that in Group II, according to long-term outcomes after hepatic resection. The positive number of Group II, according to long-term outcomes after hepatic resection. The positive number of these six variables also classified them well. CONCLUSION: Both, our new scoring system these six variables also classified them well. CONCLUSION: Both, our new scoring system and the positive number of significant prognostic factors are useful to classify patients with and the positive number of significant prognostic factors are useful to classify patients with colorectal liver metastases in the preoperative selection of good candidates for hepatic colorectal liver metastases in the preoperative selection of good candidates for hepatic resection.resection.


Management of the hepatic lymph nodes during resection Management of the hepatic lymph nodes during resection of liver metastases from colorectal cancer: a systematic of liver metastases from colorectal cancer: a systematic

review review GurusamyGurusamy KS KS, , ImberImber C C, , Davidson BRDavidson BR..

University Department of Surgery, UCL and Royal Free Hospital NHS Trust, Royal Free and University Department of Surgery, UCL and Royal Free Hospital NHS Trust, Royal Free and University College School of Medicine, London NW3 2QG, UK. [email protected] College School of Medicine, London NW3 2QG, UK. [email protected]: Hepatic lymph node involvement is generally considered a contraindication for BACKGROUND: Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. However, some advocate hepatic liver resection performed for colorectal liver metastases. However, some advocate hepatic lymphadenectomy in the presence of macroscopic involvement and others routine lymphadenectomy in the presence of macroscopic involvement and others routine lymphadenectomy. The aim of this review is to assess the role of lymphadenectomy in resection lymphadenectomy. The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. METHODS: Medline, Embase and Central databases of liver metastases from colorectal cancer. METHODS: Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. RESULTS: of 1 year were considered for inclusion. Meta-analysis was performed using Revman. RESULTS: A total of 4230 references were identified. Ten reports of nine studies including 926 patients A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients. The odds ratios for 3-year and 5-year survivals in and 246/767 (32.1%) in node-negative patients. The odds ratios for 3-year and 5-year survivals in node positive disease compared to node-negative disease were 0.12 (95% CI 0.06 to 0.24) and node positive disease compared to node-negative disease were 0.12 (95% CI 0.06 to 0.24) and 0.08 (95% CI 0.03 to 0.22). There was no randomized controlled trial which assessed the survival 0.08 (95% CI 0.03 to 0.22). There was no randomized controlled trial which assessed the survival benefit of routine or "selective" lymphadenectomy. CONCLUSION: Currently, there is no benefit of routine or "selective" lymphadenectomy. CONCLUSION: Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required.required.

HPB Surg. 2008;2008:684150

Management of the hepatic lymph nodes during resection Management of the hepatic lymph nodes during resection of liver metastases from colorectal cancer: a systematic of liver metastases from colorectal cancer: a systematic

review review GurusamyGurusamy KS KS, , ImberImber C C, , Davidson BRDavidson BR..

BACKGROUND: Hepatic lymph node involvement is generally considered a BACKGROUND: Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. contraindication for liver resection performed for colorectal liver metastases. The aim of this review is to assess the role of lymphadenectomy in resection of liver The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. metastases from colorectal cancer. METHODS: Medline, Embase and Central databases were searched using a formal METHODS: Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. considered for inclusion. Meta-analysis was performed using Revman. RESULTS: A total of 4230 references were identified. Ten reports of nine studies RESULTS: A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. including 926 patients qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, (11.3%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients.(32.1%) in node-negative patients. CONCLUSION: Currently, there is no evidence of survival benefit for routine or CONCLUSION: Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required.are required.

HPB Surg. 2008;2008:684150


resection of liver metastases, when possible, remains the preferred resection of liver metastases, when possible, remains the preferred therapy for potential cure therapy for potential cure The overall 5-year survival rates are in the range of 35%–58% in the The overall 5-year survival rates are in the range of 35%–58% in the major series reporting on the results of hepatectomy with curative major series reporting on the results of hepatectomy with curative intent intent Patients with untreated metastatic colorectal cancer have a short Patients with untreated metastatic colorectal cancer have a short median survival time of approximately 12 months median survival time of approximately 12 months Although the progress of developing effective agents has Although the progress of developing effective agents has accelerated, the median survival time of unresected patients is still accelerated, the median survival time of unresected patients is still in the range of 16–24 months, and survival beyond 5 years is in the range of 16–24 months, and survival beyond 5 years is uncommon uncommon Ablative therapies are frequently used Ablative therapies are frequently used Given that surgical resection remains the best chance for cure, Given that surgical resection remains the best chance for cure, there has been considerable interest in expanding the criteria for there has been considerable interest in expanding the criteria for resectability of patients with colorectal metastasis using other resectability of patients with colorectal metastasis using other adjunctive and adjuvant approaches. adjunctive and adjuvant approaches.

Management of Liver Metastasis: Patient Management of Liver Metastasis: Patient Selection in CRC Liver Metastases Selection in CRC Liver Metastases

Neoajuvant Chemotherapy Neoajuvant Chemotherapy

Recurrence and outcomes following hepatic resection, radiofrequency Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver ablation, and combined resection/ablation for colorectal liver

metastases.metastases.

AbdallaAbdalla EK EK, et.al. HoustonAnn Surg. 2004, et.al. HoustonAnn Surg. 2004 Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center,, TX, USA.Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center,, TX, USA.

OBJECTIVE: To examine recurrence and survival rates for patients treated with hepatic resection only, OBJECTIVE: To examine recurrence and survival rates for patients treated with hepatic resection only, radiofrequency ablation (RFA) plus resection or RFA only for colorectal liver metastases. SUMMARY radiofrequency ablation (RFA) plus resection or RFA only for colorectal liver metastases. SUMMARY BACKGROUND DATA: Thermal destruction techniques, particularly RFA, have been rapidly accepted into BACKGROUND DATA: Thermal destruction techniques, particularly RFA, have been rapidly accepted into surgical practice in the last 5 years. Long-term survival data following treatment of colorectal liver metastasis surgical practice in the last 5 years. Long-term survival data following treatment of colorectal liver metastasis using RFA with or without hepatic resection are lacking. METHODS: Data from 358 consecutive patients with using RFA with or without hepatic resection are lacking. METHODS: Data from 358 consecutive patients with colorectal liver metastases treated for cure with hepatic resection +/- RFA and 70 patients found at laparotomy to colorectal liver metastases treated for cure with hepatic resection +/- RFA and 70 patients found at laparotomy to have liver-only disease but not to be candidates for potentially curative treatment were compared (1992-2002). have liver-only disease but not to be candidates for potentially curative treatment were compared (1992-2002). RESULTS: Of 418 patients treated, 190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA RESULTS: Of 418 patients treated, 190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA only (14%), and 70 laparotomy with biopsy only or arterial infusion pump placement ("chemotherapy only," 17%). only (14%), and 70 laparotomy with biopsy only or arterial infusion pump placement ("chemotherapy only," 17%). RFA was used in operative candidates who could not undergo complete resection of disease. Overall recurrence RFA was used in operative candidates who could not undergo complete resection of disease. Overall recurrence was most common after RFA (84% vs. 64% RFA + resection vs. 52% resection only, P < 0.001). Liver-only was most common after RFA (84% vs. 64% RFA + resection vs. 52% resection only, P < 0.001). Liver-only recurrence after RFA was fourfold the rate after resection (44% vs. 11% of patients, P < 0.001), and true local recurrence after RFA was fourfold the rate after resection (44% vs. 11% of patients, P < 0.001), and true local recurrence was most common after RFA (9% of patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02). recurrence was most common after RFA (9% of patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02). Overall survival rate was highest after resection (58% at 5 years); 4-year survival after resection, RFA + resection Overall survival rate was highest after resection (58% at 5 years); 4-year survival after resection, RFA + resection and RFA only were 65%, 36%, and 22%, respectively (P < 0.0001). Survival for "unresectable" patients treated and RFA only were 65%, 36%, and 22%, respectively (P < 0.0001). Survival for "unresectable" patients treated with RFA + resection or RFA only was greater than chemotherapy only (P = 0.0017). CONCLUSIONS: Hepatic with RFA + resection or RFA only was greater than chemotherapy only (P = 0.0017). CONCLUSIONS: Hepatic resection is the treatment of choice for colorectal liver metastases. RFA alone or in combination with resection for resection is the treatment of choice for colorectal liver metastases. RFA alone or in combination with resection for unresectable patients does not provide survival comparable to resection, and provides survival only slightly unresectable patients does not provide survival comparable to resection, and provides survival only slightly superior to nonsurgical treatment.superior to nonsurgical treatment.

Neuroendocrine hepatic metastases: does aggressive Neuroendocrine hepatic metastases: does aggressive management improve survival management improve survival

TouziosTouzios JG JG, , KielyKiely JM JM, , Pitt SCPitt SC, , RillingRilling WS WS, , QuebbemanQuebbeman EJ EJ, , Wilson SDWilson SD, , Pitt HAPitt HA. . Wisconsin Ann Surg. 2005 Wisconsin Ann Surg. 2005

OBJECTIVE: The aim of this study was to determine whether aggressive management of OBJECTIVE: The aim of this study was to determine whether aggressive management of neuroendocrine hepatic metastases improves survival. SUMMARY BACKGROUND DATA: neuroendocrine hepatic metastases improves survival. SUMMARY BACKGROUND DATA: Survival in patients with carcinoid and pancreatic neuroendocrine tumors is significantly better Survival in patients with carcinoid and pancreatic neuroendocrine tumors is significantly better than adenocarcinomas arising from the same organs. However, survival and quality of life are than adenocarcinomas arising from the same organs. However, survival and quality of life are diminished in patients with neuroendocrine hepatic metastases. In recent years, aggressive diminished in patients with neuroendocrine hepatic metastases. In recent years, aggressive treatment of hepatic neuroendocrine tumors has been shown to relieve symptoms. Minimal data treatment of hepatic neuroendocrine tumors has been shown to relieve symptoms. Minimal data are available, however, to document improved survival with this approach. METHODS: The are available, however, to document improved survival with this approach. METHODS: The records of patients with carcinoid (n = 84) and pancreatic neuroendocrine tumors (n = 69) records of patients with carcinoid (n = 84) and pancreatic neuroendocrine tumors (n = 69) managed at our institution from January 1990 through July 2004 were reviewed. Eighty-four managed at our institution from January 1990 through July 2004 were reviewed. Eighty-four patients had malignant tumors, and hepatic metastases were present in 60 of these patients. Of patients had malignant tumors, and hepatic metastases were present in 60 of these patients. Of these 60 patients, 23 received no aggressive treatment of their liver metastases, 19 were treated these 60 patients, 23 received no aggressive treatment of their liver metastases, 19 were treated with hepatic resection and/or ablation, and 18 were managed with transarterial with hepatic resection and/or ablation, and 18 were managed with transarterial chemoembolization (TACE) frequently (n = 11) in addition to resection and/or ablation. These chemoembolization (TACE) frequently (n = 11) in addition to resection and/or ablation. These groups did not differ with respect to age, gender, tumor type, or extent of liver involvement. groups did not differ with respect to age, gender, tumor type, or extent of liver involvement. RESULTS: Median and 5-year survival were 20 months and 25% for the Nonaggressive group, RESULTS: Median and 5-year survival were 20 months and 25% for the Nonaggressive group, >96 months and 72% for the Resection/Ablation group, and 50 months and 50% for the TACE >96 months and 72% for the Resection/Ablation group, and 50 months and 50% for the TACE group. The survival for the Resection/Ablation and the TACE groups was significantly better (P < group. The survival for the Resection/Ablation and the TACE groups was significantly better (P < 0.05) when compared with the Nonaggressive group. Patients with more than 50% liver 0.05) when compared with the Nonaggressive group. Patients with more than 50% liver involvement had a poor outcome (P < 0.001). CONCLUSIONS: These data suggest that involvement had a poor outcome (P < 0.001). CONCLUSIONS: These data suggest that aggressive management of neuroendocrine hepatic metastases does improve survival, that aggressive management of neuroendocrine hepatic metastases does improve survival, that chemoembolization increases the patient population eligible for this strategy, and that patients chemoembolization increases the patient population eligible for this strategy, and that patients with more than 50% liver involvement may not benefit from an aggressive approach.with more than 50% liver involvement may not benefit from an aggressive approach.

Resection versus no intervention or other surgical Resection versus no intervention or other surgical interventions for colorectal cancer liver interventions for colorectal cancer liver metastases. metastases. Al-Al-AsfoorAsfoor A A, Fedorowicz Z, Lodge M., Fedorowicz Z, Lodge M.

– BACKGROUND: About one in four of patients with metastatic colorectal cancer have metastases isolated to BACKGROUND: About one in four of patients with metastatic colorectal cancer have metastases isolated to the liver, of which 10% to 25% are eligible for ablation of the liver metastases, improving the five year the liver, of which 10% to 25% are eligible for ablation of the liver metastases, improving the five year survival rate.Treatments include hepatic resection and other modalities using cryosurgery and survival rate.Treatments include hepatic resection and other modalities using cryosurgery and radiofrequency thermal ablation. Although new modalities allow safe ablation of liver metastases without the radiofrequency thermal ablation. Although new modalities allow safe ablation of liver metastases without the need for surgical intervention, there are still no clear guidelines on the appropriate management of patients need for surgical intervention, there are still no clear guidelines on the appropriate management of patients with colorectal cancer and hepatic metastases. OBJECTIVES: The primary objectives were to compare with colorectal cancer and hepatic metastases. OBJECTIVES: The primary objectives were to compare resection of liver metastases to no intervention and other modalities of intervention (including cryosurgery resection of liver metastases to no intervention and other modalities of intervention (including cryosurgery and radiofrequency ablation) in terms of the benefits and harms for each intervention. SEARCH and radiofrequency ablation) in terms of the benefits and harms for each intervention. SEARCH STRATEGY: Searches were conducted of the Cochrane Central Register of Controlled Trials, MEDLINE STRATEGY: Searches were conducted of the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases up to October 2006. In addition, references were scrutinized in identified eligible and EMBASE databases up to October 2006. In addition, references were scrutinized in identified eligible trials. SELECTION CRITERIA: Only randomized controlled trials reporting patients (regardless of age and trials. SELECTION CRITERIA: Only randomized controlled trials reporting patients (regardless of age and sex) who had had curative surgery for adenocarcinoma of the colon or rectum, had been diagnosed with sex) who had had curative surgery for adenocarcinoma of the colon or rectum, had been diagnosed with liver metastases and who were eligible for liver resection (i.e. with no evidence of primary or metastatic liver metastases and who were eligible for liver resection (i.e. with no evidence of primary or metastatic cancer elsewhere) were considered. DATA COLLECTION AND ANALYSIS: Two review authors cancer elsewhere) were considered. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a form designed for this review. Discrepancies were resolved by independently extracted data using a form designed for this review. Discrepancies were resolved by consensus. MAIN RESULTS: Only one trial involving 123 people (87 male 36 female) was included. The consensus. MAIN RESULTS: Only one trial involving 123 people (87 male 36 female) was included. The data from this ten year prospective, randomized clinical trial suggest that hepatic cryosurgery is effective in data from this ten year prospective, randomized clinical trial suggest that hepatic cryosurgery is effective in the treatment of resectable and nonresectable liver metastases. The results show intra-operative tumor the treatment of resectable and nonresectable liver metastases. The results show intra-operative tumor reduction (>/=90% or </= 97%) and extended higher survival in these patients. The study indicated a five reduction (>/=90% or </= 97%) and extended higher survival in these patients. The study indicated a five year and ten year survival rate of 44% and 19% after cryosurgery, respectively. However, it was not year and ten year survival rate of 44% and 19% after cryosurgery, respectively. However, it was not possible to separate out and unravel the outcomes data that related only to the participants (66.6%) with possible to separate out and unravel the outcomes data that related only to the participants (66.6%) with liver metastases from colorectal cancer as opposed to those with liver metastases from other primary liver metastases from colorectal cancer as opposed to those with liver metastases from other primary tumors. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support a single approach, tumors. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support a single approach, either surgical or non-surgical, for the management of colorectal liver metastases. Therefore, treatment either surgical or non-surgical, for the management of colorectal liver metastases. Therefore, treatment decisions should continue to be based on individual circumstances and clinician's experience. The authors decisions should continue to be based on individual circumstances and clinician's experience. The authors conclude that local ablative therapies are probably useful, but that they need to be further evaluated in a conclude that local ablative therapies are probably useful, but that they need to be further evaluated in a randomized controlled trial.randomized controlled trial.

Cochrane Database Syst Rev. 2008 Apr

Analysis of prognostic factors influencing long-term survival Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic colorectal cancer after hepatic resection for metastatic colorectal cancer

Arru M,et al Italy, World J Surg. 2008Arru M,et al Italy, World J Surg. 2008

The retrospective analysis n=297 liver resections for colorectal The retrospective analysis n=297 liver resections for colorectal metastasesmetastases

The univariate analysis revealed a statistically significant difference (p < The univariate analysis revealed a statistically significant difference (p < 0.05) in overall survival in relation to0.05) in overall survival in relation to: : grade of differentiation of the primary cancer (5-year survival of grade of differentiation of the primary cancer (5-year survival of grades G1-G2 vs grades G3-G4: 30.7% vs 14.4%, p = 0.0016), grades G1-G2 vs grades G3-G4: 30.7% vs 14.4%, p = 0.0016), preoperative CEA level > 5 and > 200 ng/ml (5-year survival of CEA < preoperative CEA level > 5 and > 200 ng/ml (5-year survival of CEA < 5 ng/ml vs CEA > 5 ng/ml: 51.1% vs 15.5%, p = 0.0016; 5 ng/ml vs CEA > 5 ng/ml: 51.1% vs 15.5%, p = 0.0016; 5-year survival of CEA < 200 ng/ml vs CEA > 200 ng/ml: 27.9% vs 5-year survival of CEA < 200 ng/ml vs CEA > 200 ng/ml: 27.9% vs 17.4%, p = 0.0001), 17.4%, p = 0.0001), diameter of major lesions > 5 cm (5-year survival of diameter < or = 5 diameter of major lesions > 5 cm (5-year survival of diameter < or = 5 cm vs > 5 cm: 30.0% vs 18.8%, p = 0.0074), cm vs > 5 cm: 30.0% vs 18.8%, p = 0.0074), disease-free interval between primary tumour and liver metastases disease-free interval between primary tumour and liver metastases longer than 12 months (5-year survival of patients with disease-free longer than 12 months (5-year survival of patients with disease-free interval < or = 12 months vs > 12 months: 23.0% vs 36.1%, p = interval < or = 12 months vs > 12 months: 23.0% vs 36.1%, p = 0.042),0.042), high MSKCC-CRS (5-year survival of MKSCC-CRS 0-1-2 vs 3-4-5: high MSKCC-CRS (5-year survival of MKSCC-CRS 0-1-2 vs 3-4-5: 36.4% vs 1 6.3%, p = 0.017). 36.4% vs 1 6.3%, p = 0.017).


General criteria for fitnessGeneral criteria for fitness

Specific Criteria that decides the outcome Specific Criteria that decides the outcome in terms of: in terms of:

- Risk of recurrence- Risk of recurrence - Survivals: Disease free and overall- Survivals: Disease free and overall

Predictive factors for outcome of a therapyPredictive factors for outcome of a therapy

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Management Of Liver M E T A S T A S I S Patient Selection

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