Colorectal cancer with liver metastases

Occur in approximately 60% of the 145,000 patients in the U.S. diagnosed with colon cancer.

It is the most common site of distant failure and cause of mortality in patients with colon cancer.

The liver is the most common side of metastases in patients with colorectal cancer and accounts for at least 2/3 of all CRC deaths.

Approximately 25% of newly diagnosed patients present with liver metastases, and 30-50% of colorectal cancer patients develop liver metastases sometomes during their course.

40-50% of patients with colorectal cancer have synchronous liver metastases.

Only available treatment associated with long term survival in colorectal cancer is resection.

Without chemotherapy surgical resection will not be possible in 70-90% of patients with liver metastases from colorectal cancer.

Chemotherapy initiated to promote resectability showed be aimed at a short course of treatment and surgery performed as soon as the metastasis become resectable.

Neoadjuvant chemotherapy for resectable metastatic colon cancer increases survival.

Complete resection rates of liver metastases of CRC are 11-33% following chemotherapy with leucovorin, 5-FU, and oxaliplatin or with leucovorin, 5-FU and CPT-11.

Following resection of liver metastases in colon cancer the 5-year survival ranges from 37-58% in recent studies.

Only 10-20% of patients with colorectal cancer are eligible for surgical resection.

In colon cancer surgery aims at complete tumor removal because incomplete resection has a similar outcome as non-resected patients.

CT scan and MRI are he best methods for detection of metastasis from colorectal cancer.

For lesions less than 10 mm MRI is more sensitive than CT scan.

Preoperative high-quality MRI and/or CT scan for mapping liver metastases is required.

Ultrasound is a useful intraoperative staging and contrast enhancement may improve sensitivity of intraoperative ultrasound.

High-quality CT scans of the chest and pelvis are recommended prior to surgical resection of hepatic metastases.

PET scan may be helpful preoperative test to rule out extrahepatic disease.

In colon cancer resection of hepatic disease vs. non resection in a series of 252 patients resulted in a 5 year survival rate of 25% vs., 2% , respectively (Wagner).

In well selected patients with colon cancer and liver metastases 17-25% of patients my achieve cure after hepatic resection of metastases (Tomlinson).

10 mm is the recommended surgical margin for colon metastases.

The standard treatments for hepatic oligometastases is surgical resection.

Only 25% of patients with hepatic oligometastatic disease are eligible for surgical resection because of medical or technical contraindications.

There is a higher rate of postoperative morbidity in patients who undergo open surgery for resection of liver metastases compared with those who undergo laparoscopic resection. (22.8% vs 20.2%, respectively, with fewer major complications reported in the laparoscopy group than in the open surgery group.

Dindo–Clavien grades III-V, 6.7% vs 8.5%, respectively; P = .03), and shorter lengths of stay observed for the laparoscopy group versus the open surgery group (median duration, 3 days vs 5 days, respectively; P = .02).

An increasing proportion of patients can benefit from the advantages of laparoscopic surgery for liver metastases from colorectal cancer, even those requiring procedures with a high degree of technical complexity.

Micrometastases supplied by portal vein and measurable metastatic disease vascularized by the hepatic artery.

Patients with minimal exposure to chemotherapy and low hepatic tumor burden with colorectal cancer have a better overall survival with radioembolization with ytrium-90 (Abbott AM et al).

Treatment with radioablation with ytrium-90 in patients with metastatic colorectal cancer median survival of 11.6 months in the above study.

Stereotatic body radiotherapy allows delivery of focal ablative dose to hepatic metastases while sparing the normal hepatic tisue and surrounding organs at risk.

With stereotactic radiotherapy between one and five large individual daily fractions of radiotherapy are administered target only to hepatic metastases and spare normal liver.

Stereotactic radiotherapy is effective in controlling lesions that are larger in diameter than those with radioablation and is affected in controlling lesions adjacent to large blood vessels where radio frequency ablation is ineffective in these lesions.

Local control in patients with 5 or fewer lesions ranges between 62% and 92% and 2 year overall survival at 30% in a number of studies.

Intratumoral arterial radiation therapy with ytrium 90 is embedded with microspheres 25 to 40 microm in diameter.

Radio embolization with selective internal radiotherapy can be done is an outpatient procedure in which radioactive particles are delivered via the hepatic artery, which feeds very metastatic tumors.

Microparticles are permanently embedded in the tumor and deliver high doses of radiation locally in the tumor mass.

With this type of radiation decay, hi-energy radiation travels only a few millimeters away from the sphere and normal adjacent liver is not subjected to radiation injury.

Metastatic tumors are efficient taking up therapeutic agents because cytokines cause excessive abnormal arterial blood vessel proliferation.

The arterial density in around metastatic lesions can be up to 200 times higher than normal liver parenchyma.

In radiofrequency ablation/microwave ablation, the tumor should be no larger than 3 cm, should not be lying on a blood vessel, and should not be on the surface of the liver or within 1 cm of the stomach, duodenum, or large bile ducts.

Similar constraints are present for a stereotactic body radiotherapy, but are less stringent.

With stereotactic body radiotherapy large tumors can be treated, as can multiple tumors, but usually not more than three, as long as 700 mL of the liver is protected from radiation.

With radiotactic body radiotherapy when the tumor is within 1 cm of the stomach or the duodenum, the radiation dose must be reduced

When treating liver metastases, by whatever modality the main consideration of treatment is to preserve 700 mL of functional liver.

Local control rate is greater than 90% for tumor masses smaller than 3 cm and is greater than 90% with stereotactic body radiotherapy in the lesions that are less than 6 cm in diameter.

The addition of radio frequency ablation to chemotherapy is associated with a better progression free survival.

In a review of regional therapies for Colorectal Liver metastases with analysis of 4100 articles there was either insufficient evidence or evidence against trans arterial chemotherapy or drug eluding bead trans arterial chemotherapy, or or trans arterial radio embolization with internal radio therapy, and hepatic arterial infusion (Karanicolas P).
The addition of perioperative systemic treatment for resectable colorectal liver, metastases, improves disease free survival but not overall survival (Soboo MB).

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