Metastasis Liver

Intraarterial infusion of microspheres containing adriamycin was used for the local treatment of breast cancer and recurrent breast cancer with liver metastases (123). A reduction in tumor size was noted when the microspheres were injected into the internal and lateral thoracic arteries for treatment of the primary tumor. However, hepatic artery injection for liver metastases resulted in improvement in only one of three patients treated. 

Following resection of liver metastases, infusion of chemotherapy through the portal vein provides an additional adjuvant treatment approach. Historically 5-FU and floxuri-dine have been the agents used most commonly for hepatic portal vein infusion owing to their high metabolism in the liver. Although some studies demonstrate a decrease in recurrence rates, the value of portal vein infusion of chemotherapy for colon cancer remains to be determined.25 Table 88-4 summarizes adjuvant treatment recommendations for colon cancer. 

Sundin A, Ahlstrom H, Graf W, Magnusson A (1994) Computed tomography of experimental liver metastases using an iodinated hepatocyte-specific lipid emulsion a correlative study in the nude rat. Invest Radiol 29 963... 

Raju PI, Maruyama Y, DeSimone P, et al. Treatment of liver metastases with a combination of chemotherapy and hyperfractionated external radiation therapy. Am J Clin Oncol 1987 10 41-43. 

Robertson JM, Lawrence TS, Walker S. The treatment of colorectal liver metastases with conformal radiation therapy and regional chemotherapy. Int J Rad Oncol Biol Phys 1995 32 445-450. 

Paclitaxel s large volume of distribution indicates significant tissue binding. The drug is extensively metabolized by the liver, and doses must be reduced in patients with abnormal liver function or with extensive liver metastases. Very little of the drug is excreted in the urine. 

Initial staging M-staging. Routine staging workup is based on conventional imaging such as CT and MRI. In the review by Reske et al., [ F]-FDG-PET detected unsuspected extrathoracic metastases in 12% of the cases. The calculated sensitivity and specificity for detection of distant metastases were 94% and 97%, respectively. [ F]-FDG-PET also revealed to be a useful tool in the assessment of adrenal masses and suspected liver metastases. 

F. H. Corstens, W.J. Oyen, Value of positron emission tomography with [F-18] fluorodeoxyglucose in patients with colorectal liver metastases A prospective study, J. Clin. Oncol. 20(2) (2002) 388-395. 

An earlier cross sectional study had found that the PME/PDE ratio was a measure of disease severity in chronic hepatitis-C. ° More recently, it was found that this ratio may also serve as a biomarker of response to treatment with antiviral therapy. ° Whereas non-responders had similar or even elevated PME/PDE initially, that ratio declined from 0.27 0.02 (standard error) to 0.16 0.01 after treatment (p<0.001) in responders. Liver resection is a common therapy for liver metastases. Prior portal vein embolization (PVE) of the resected lobe results in h) ertrophy of the remaining contralateral lobe. Phosphorus-31 MRSI has been used to monitor metabolism of the regenerating lobe after PVE. ° ... 

Matsuyama R, Togo S, Shimizu D et al. Predicting 5-fluorouracil chemosensitivity of liver metastases from eoloreetal eaneer using primary tumor specimens three-gene expression model predicts clinical response. Int J Cancer 2006 19 406-413. 

Wittig, . M., Kaulen, H., Thees, R., Schmitt, C., Knolle, P., Stock, J., Meyer zum Buschenfelde, . H., and Dippold, W. (1996). Elevated serum E-selectin in patients with liver metastases of colorectal cancer. Eur. ]. Cancer 32A, 1215-1218. 

Normalization of organ function is another useful indicator of drug effectiveness. Examples of such improvement include the normalization of liver function (eg, increased serum albumin) in patients known to have liver metastases and improvement in neurologic findings in patients with cerebral metastases. 

Ashraf S, Crowe R, Loizidou MC, Turmaine M, Taylor I, Burnstock G. The absence of autonomic perivascular nerves in human colorectal liver metastases. Br J Cancer 1996 ... 

The oncolytic viruses include adenovirus, measles, reovirus, vesicular stomatitis virus (VSV),HSV,poxvirus, and vaccinia. Specific examples include (1) ONYX-015, which is an adenoviral oncolytic virus, administered to patients with liver metastases of colorectal cancer and pancreatic cancer [29], (2) Reolysin, which is an oncolytic reovirus administered to patients with glioma [30], and (3) MV-CEA, which is an oncolytic measles virus expressing carcinoembryonic antigen, administered to patients with ovarian cancer [31]. Some oncolytic viruses are wild type and are apparently not pathogenic in humans, such as the Newcastle disease virus (NDV), which is an RNA avian paramyxovirus. PV701, a naturally attenuated, replication-competent strain of NDV, has been administered to patients with advanced solid tumors [32], The applicability of oncolytic viruses as a therapy for clinical oncology trials is due to their potential selectivity the ability to kill tumor cells but not normal cells. However, the level of attenuation of viral replication in normal cells is limited for most oncolytic vectors. 

Kissel J, Brix G, Bellemann ME et at. (1997) Pharmacokinetic analysis of 5-[18F]fluorouraciI tissue concentrations measured with positron emission tomography in patients with liver metastases from colorectal adenocarcinoma. Cancer Res 57 3415-3423... 

Hepatic and renal function. Patients with advanced cancer may have impaired liver function due to the presence of liver metastases. In this case drug doses may need to be adjusted. In the case of the FOLFOX regimen, 5-fluorouracil dose may need to be reduced if the impairment is moderate or severe. Mrs KT s baseline liver function tests indicate a normal liver function, but these parameters should be monitored carefully throughout treatment. Reduced renal function may also necessitate a decrease in drug dosage. In the case of the FOLFOX regimen, oxaliplatin is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min). 

This may be due to liver capsular pain from liver metastases. Mrs CR s abnormal liver function tests may indicate this. If metastatic cancer has spread to her liver, the resultant disease within the liver capsule may cause pain. Another possible cause could be the high dosage of senna that she is taking (8 tablets a day) -excessive dosages of stimulant laxatives such as senna can cause abdominal cramp and pain due to their effect of increasing intestinal motility. 

CT scan to objectively measure disease response (lung and liver metastases) -after three to four cycles of treatment,... 

Bresalier, R. S., Hujanen, E. S., Raper, S. E., Roll, F. J., Itzkowitz, S. H., Martin, G. R. and Kim, Y. S. (1987). An animal model for colon cancer metastasis establishment and characterization of murine cell lines with enhanced liver-metastasizing ability. Cancer Res. 47, 1398-1406. 

Calorini, L., Marozzi, A., Byers, H. R., Waneck, G. L., Lee, K. W., Isselbacher, K. J. and Gattoni-CelU, S. (1992). Expression of a transfected H-2Kb gene in B16 cells correlates with suppression of liver metastases in triple immunodeficient mice. Cancer Res. 52, 4036-4041. 

---