Liver tumors

The carcinogenic potential of hexachloroethane has not been evaluated following chronic inhalation or dermal exposure. Hexachloroethane increased the incidence of renal tumors in male rats (NTP 1989) following chronic oral exposure. However, these tumors were associated with renal hyaline droplets and, thus, are unique to male rats. Although kidney damage was present in female rats after lifetime exposures to 80 and 160 ppm hexachloroethane, there was no increase in renal tumors. Liver lesions and liver tumors were found in mice following long-term oral exposure (NTP 1977). 

In hamsters, 0.3% DCB in the diet produced transitional cell carcinomas of the bladder and some liver cell tumors. Liver tumors were also found in mice exposed to DCB. Female dogs fed 8mg/kg/day for a period of 6-7 years had hepatocellular carcinomas and papillary transitional cell carcinomas of the urinary bladder tumors were absent in untreated controls. ... 

Imamura, M., Shiratori, Y., Shiina, S., Sato, S., Obi, S., Okudaira, T., Teratani, T., Kato, N., Akahane, M., Ohtomo, K., Minami, M., Omata, M. Power Doppler sonography for hepatocellular carcinoma factors affecting the power Doppler signals of the tumors. Liver 1998 18 427-433... 

Biodistribution of liposomes is a very important parameter from the clinical point of view. Liposomes can alter both the tissue distribution and the rate of clearance of the drug by making the drug take on the pharmacokinetic characteristics of the carrier (10, 11). The pharmacokinetic variables of the liposomes depend on the physiochemical characteristics of the liposomes, such as size, surface charge, membrane lipid packing, steric stabilization, dose, and route of administration. As with other microparticulate delivery systems, conventional liposomes are vulnerable to elimination from systemic circulation by the cells of the reticuloendothelial system (RES) (12). The primary sites of accumulation of conventional liposomes are the tumor, liver, and spleen compared with non-liposomal formulations (13). Many studies have shown that within the first 15-30 min after intravenous administration of liposomes between 50 and 80% of the dose is adsorbed by the cells of the RES, primarily by the Kupffer cells of the liver (14-16). 

Tumor Liver Spleen Lung Tissue Types... 

Using normal, cirrhotic and tumorous liver tissues, Lim et al. (2002) found that 21 proteins had a significant change in expression. Of these proteins, lamin B1 was proposed as a marker for cirrhosis as this protein was highly expressed in the cirrhotic tissue when compared to the normal liver tissue. However, a non-invasive method for its detection in cirrhosis, if any, was not proposed. 

The final step of the nuclear medicine procedure would be to reconstruct the SPECT study, to fuse it with the anatomic images (CT or MRl) and to delineate (if possible) the tumour regions and the non-tumoral liver areas in the transaxial images to calculate the T/N ratio. 

Finally, the activity values of the tumoral and non-tumoral liver can be obtained from the transaxial fused images. These will be used to calculate microsphere activity to deliver according to the partition model. In our protocol, we draw five circular ROIs in the hottest tumoral nodules and another five in the non-tumoral liver (all of them of the same size). Alternatively, in the case of a big tumoral mass, we position the five ROIs in five non-consecutive areas of the mass. The mean activity value for the tumoral and non-tumoral ROIs is obtained, and it will be used in the dose calculation formula (Fig. 7.5). 

Fig. 7.5. Transaxial slices from an MAA SPECT study. Five ROIs have been drawn in the tumoral areas (red) and another five in the non-tumoral liver (green). All regions are the same size to facilitate dose calculation...

Group II patients are also good candidates for the treatment. The main limitation for the delivered activity is uptake in non-tumoral liver, but with dose calculation based on the ROI drawn in the fusion images the procedure is very safe. 

Whether or not to treat group III subjects is the most difficult decision to be made in the preliminary evaluation. A consensus within the multidisciplinary team has to be achieved. Using the dose limitation of 40 Gy to the non-tumoral liver, the estimated dose calculated for the tumours is not as high... 

Fig. 7.8. Perfect match among the tumoral nodules in CT and MAA uptake. Almost no activity can be seen in the non-tumoral liver. This patient should be considered for a high radiospheres dose due to the low probability of healthy liver damage...

Fig. 7.9a,b. Patient with extensive right lobe disease (a). Fusion images show that some of the lesions present significant MAA uptake, while mild diffuse uptake can be seen in the rest of the nodules and in the non-tumoral liver (b)... 

An MAA test to measure the degree of intrahe-patic/intratumoral shunt to the lung, to detect any possible misplacement of SIR-Spheres in the gastrointestinal tract and to evaluate the relative amount of activity going to the liver tumors and the non-tumoral liver. 

Activity depends on the body surface area (BSA) and the extent of tumor liver involvement. BSA in square meters was calculated using standard nomograms. Tumor liver involvement was measured on CT or MRI. The activity was then calculated using the formula Activity (GBq) = (BSA - 0,2) + (tumor volume/total liver volume). The calculated activity was reduced for patients with lung shunt from 10% to 20% and treatment was contraindicated if the lung shunt was higher than 20%. For those patients receiving lobar therapy, the activity could be reduced proportionally to the relative volume of the treated lobe compared to whole liver volume. 

In this method, the maximal activity that remained safe for the lung and the non-tumoral liver was calculated. The estimated radiation delivered to the lung and the non-tumoral liver had to be lower than 20 Gy and 60 Gy, respectively (30 Gy for the non-tumoral liver since October 2004). 

Fig. 10.4a-c. Serious RE-induced liver toxicity was observed as a result of a significant proportion of the injected SIR-Spheres reaching the non tumoral liver, a The MAA scan obtained before RE shows significant activity in non-tumoral areas and tumors not clearly depicted. b,c CT or MRI scan of the liver before and 5 months after RE revealing a 28% decrease in total liver volume... 

Fig. 14.1. Treatment algorithm for patients with neuroendocrine tumor liver metastases...

Most patients with neuroendocrine tumor liver metastasis have extensive bilobar involvement. As only one lobe is treated during each embolization session, most patients require a minimum of two treatment sessions in order to treat the entire liver, depending on the hepatic arterial anatomy. An interval of 4 to 6 weeks is recommended between treatment sessions to allow for liver function recovery. 

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