Metastatic colorectal liver cancer, liver cancer, colorectal cancer

1. METASTATIC COLORECTAL
LIVER CANCER
DR BASHIR BIN YUNUS
GENERAL SURGERY UNIT
AKTH.

2. OUTLINE
• INTRODUCTION
• RISK FACTORS
• EVALUATION
• TREATMENT OPTIONS
• SURGERY
• CHEMOTHERAPY
• LOCAL TUMOUR ABLATION
• RADIOTHERAPY
• SURVELLANCE
• CONCLUSION

3. INTRODUCTION
• 25 - 35% of patients presents with synchronous metastasis.
• 50 – 60 % of patients will eventually develop metastasis, mostly
within 2 years of detecting the primary.
• 5 year survival is 2 % if unresectable and 50% if resectable

4. RISK FACTORS FOR SPREAD
•Tumor Factors
• Disease stage
• High-grade tumor (poorly differentiated)
• Tumor location
• Obstruction/perforation
• Venous invasion
• Perineural invasion
• Mucin production
• Diminished stromal immune reaction
• Aneuploidy
• Mutant p53 gene expression
• Low microsatellite instability

5. RISK FACTORS FOR SPREAD
• Technical Factors
• Inadequate resection margins (radial, distal, mesorectal)
• Implantation of exfoliated cells
• Tumor location (pelvis and splenic flexure is anatomically and technically
more difficult)

6. PRE-OPERATIVE EVALUATION
• Colonoscopy
• Chest / abdominal/ pelvic CT; most sensitive in detecting pulmonary
metastasis. It detects 95% of lesion > 1 cm
• CBC, Platelets, Chemistry
• CEA
• Determination of tumor K- RAS status
• Needle biopsy – if clinically indicated
• PET – CT only if potentially surgically curable M1 disease. PET scan
most informative. 92-100 % sensitivity and 85-100 % specificity

7. TREATMENT OPTIONS
• SURGERY ; only surgery is associated with survival advantage.
• Spread of colorectal cancer occurs in a step wise pattern-primarily to
liver and then from liver to other sites.
• Treatment of liver metastasis with the ability of liver to regenerate
results in prevention of metastasis to other sites and results in
increased survival.
• Five year survival rate after resection range from 24-58 %, averaging
40%. Surgical mortality is generally < 5 %

8. CRITERIA FOR RESECTION
• GENERAL CRITERIA
• Good performance status
• Absence of extra hepatic disease
• SPECIFIC CRITERIA THAT DECIDES THE OUTCOME
• Risk of recurrence- clinical score for CRC
• ANATOMICAL CRITERIA FOR RESECTABILITY
• Number of metastesis < 4
• Tumour ≤ 3 cm
• Relationship with the portal and hepatic veins.
• Resection margin < 1 cm

9. Clinical Risk Score
• Nodal status of the primary disease
• Free interval from the discovery of the primary to the discovery of the
liver metastases of <12 months
• Number of tumors >1
• Preoperative CEA level of >200 ng/mL
• Size of the largest tumors >5 cm
• Each positive criterion is assigned one point. 5-year survival is 60%
with score of 0 points, and falls to 14% in patients with 5 points.

10. • Redefining the resectability of colorectal liver metastasis:
• No more defined by strict criteria on: numbers, size and distribution
of liver metastases
• The determination of resectability is now based on:
- whether it is possible to remove all known disease
- while leaving behind an adequate functional remnant liver

11. New paradigm:4 main Criteria for
Resectability of Colorectal Liver Metastases
• An R0 resection of both the intra- and extrahepatic disease sites must
be feasible.
• At least two adjacent liver segments need to be spared.
• Vascular inflow and outflow, as well as biliary drainage to the
remaining segments, must be preserved.
• The volume of the liver remaining after resection (i.e., the future liver
remnant) must be adequate.

12. The volume of the liver remaining after resection (i.e., the future liver
remnant) must be adequate. which usually means at least;
• 20% of the total estimated liver volume for normal parenchyma
• 30%–60% if the liver is injured by chemotherapy, steatosis, or
hepatitis
• 40%–70% in the presence of cirrhosis, depending on the degree of
underlying hepatic dysfunction

13. CONTRAINDICATIONS TO LIVER RESECTION
• Non-treatable primary tumor.
• Widespread pulmonary disease.
• Peritoneal disease.
• Extensive nodal disease, such as retroperitoneal or mediastinal
nodes.
• Bone or CNS metastases.
• those who progress on systemic chemotherapy

14. TECHNIQUE
• Anatomical resection
• Segmentectomy
• hemihepatectomy
• Non Anatomical resection
• Wedge resection
• Anatomical resection preferred due to low recurrance rate.

15. How to increase RESECTABILITY
• Portal Vein Occlusion
• Two-Stage Hepatectomy
• Downstaging chemotherapy
• Local Ablation Techniques

16. CHEMOTHERAPY
• Neoadjuvant chemotherapy
• Resectable liver metastases:
• Facilitate surgery
• Obtain predictive and prognostic information
• Early systemic therapy for poor-prognosis patients
• Conversion chemotherapy
• Unresectable liver metastases: Allow R0 resection via downsizing
• Postoperative (adjuvant) chemotherapy

17. CONVENTIONAL CHEMOTHERAPY
• thyimidilate synthase inhibitor; 5FU, capecitabin, raititrexed
• Topoisomerase I inhibitor ; irinotican
• Alkylating agent ; oxaliplatin

18. Liver Toxicities
• 5-FU: hepatic steatosis, associated with increased postoperative morbidity-
yellow liver
• Irinotecan: non-alcoholic steatohepatitis (especially in obese patients), can
affect hepatic reserve and increase morbidity and mortality after
hepatectomy - orange liver
• Oxaliplatin: hepatic sinusoidal obstruction syndrome, does not appear to
be associated with increased risk of perioperative death - blue liver
Both response rate and toxicity should be considered when selecting
preoperative Chemo in patients with colorectal liver metastases

19. • The use of chemotherapy as an adjunct to liver resection has resulted
in a 5-year survival in the range of 37 to 58%.
• Ten-year survival is reported to be between 16 to 30%.

20. RECURRENT LEISION
• Common site of recurrence after hepatic resection is liver.
• Liver is the sole site of recurrance in 15-40 % of cases.
• Repeat hepatectomy considered in patient with good clinical reserve
and absence of extra hepatic disease

21. VANISHING HEPATIC LEISION
• Complete radiological response occurs in 6-9% of patients after
noeadjuvant chemotherapy
• Due to pathologically complete response or inability of imaging to
pick leision due to hepatic stenosis.

22. • There is not a chemotherapy schedule indicated as standard
treatment in neoadjuvant setting of colorectal liver metastases: all
schedules could be used
• Triplet seems to be more effective
• Adding molecular drugs(targeted therapy), there is an activity
increase in term of response rate and resectability
• Prospective studies on predictive factors of response and resectability
could be useful to select the better treatment for each patient

23. LOCAL ABLATION
Indication for ablation is in patients:
• who do not meet the criteria for resectability
• but are candidates for liver-directed therapy based upon the presence
of liver-only disease.
• complete margin-negative ablation can be achieved

24. CRYOABLATION
• Freeze thaw cycles using liquid nitrogen at -100⁰C.
• Complications;
• Biliary abscess
• Myoglobinuria
• Hemorrhage
• Coagulopathy
• Cryoshock

25. RADIOFREQUENCY ABLATION
• Radiofrequency high alternating current 460 khz. Temp 60⁰C causing
coagulative necrosis. Effective in tumours upto 5 cm.
• Complications;
• Biloma
• Biliary fistula
• Stricture
• abscess

26. OTHER LOCAL ABLATION
• Laser interstitial thermal therapy (LITT)
• Microwave coagulation therapy
• Intratumoral injection of alcohol

27. RADIOTHERAPY
• STEREOTACTIC BODY RADIATION
• SELECTIVE INTERSTITIAL RADIATION THERAPY

28. SURVEILLANCE AFTER METASTECTOMY
• Surveillance strategy for patients with stage IV disease who are
rendered surgically NED (no evidence of disease)
• CEA every three months for two years, then every six months for
three to five years
• CT of the chest/abdomen and pelvis every three to six months for two
years, then every 6 to 12 months up to a total of five years
• Colonoscopy in one year; if no adenoma repeat in three years, then
every five years; if adenoma is found, repeat in one year

29. Conclusion
• Metastasis in colorectal cancer follows a stepwise pattern.
• Liver is the most common site and most often the first site to get
involved.
• Median survival is around 15 months and 5 yr survival less than 2 % in
patients without any treatment. Surgical resection improves the 5 yr
survival rate to around 50 %
• Intent of surgical resection is cure.
• Resectable metastatic leisions are best managed with surgical
resection.