Complications of hepatic artery infusion: a review of 4580 reported cases.

PURPOSE: The resurgence of hepatic artery infusion (HAI) for the treatment of colorectal liver metastases has been dampened by concern over its complications. We have reviewed the incidence and frequency of complications associated with HAI and discussed the factors associated with these complications. METHODS: A PUBMED search was conducted from 1950-2001 using various combinations of these keywords: hepatic arterial infusion, colorectal carcinoma, complications, and trials. The main inclusion criterion was the reporting of HAI complications. The main exclusion criterion was duplicated patients. Extracted data included chemotherapeutic agents, catheter technique, drug toxicities, and catheter related complications. Relative risks and 95% confidence intervals were calculated. RESULTS: We reviewed 437 articles/abstracts and included 101 studies. 4580 patients with 4582 toxicities and complications were reported. The mortality rate was 1%. The most common toxicities were: GI symptoms 22%, chemical hepatitis 19%, and bone marrow toxicity 8%. 5-fluorouracil (5-FU) HAI had statistically significant risk for GI symptoms and bone marrow toxicity. Floxuridine (FUDR) HAI had statistically significant risk for chemical hepatitis, sclerosing cholangitis, and biliary toxicity. The most common catheter complications were: hepatic artery occlusion 6%, catheter thrombosis 5%, and catheter displacement 7%. CONCLUSIONS: This literature review of the complications of HAI confirms a low mortality associated with HAI. Sclerosing cholangitis and chemical hepatitis are associated with the use of FUDR, while the use of 5-FU is associated with bone marrow toxicity. Our observations support the development of hepatic cytoprotective agents and other effective anti-tumor agents to improve the results and morbidity of HAI for colorectal liver metastases.

Vitamin E succinate promotes breast cancer tumor dormancy.

BACKGROUND: Vitamin E succinate (VES) is the most potent antitumor analogue of vitamin E. Despite many reports of VES's antitumor activity in vitro, there is little information about its antitumor effects in vivo. MATERIALS AND METHODS: We investigated the effect of VES on the growth of human breast cancer cells in vitro and in vivo. RESULTS: VES decreased cell viability in MDA-MB-231 and MCF-7 human breast cancer cells. Although VES increased apoptosis in MDA-MB-231 cells, it had no effect on apoptosis in MCF-7 cells. The inhibitory effect of VES on cell growth was specific for the intact molecule because a markedly reduced effect was noted when either vitamin E or succinic acid was administered alone. VES inhibited the growth of MDA-MB-231 cells in nude mice. Also, VES was found to inhibit vascular endothelial growth factor (VEGF) gene expression in MDA-MB-231 cells. CONCLUSIONS: VES inhibits the growth of breast cancer cells in vitro and in vivo. This is the first report of VES inhibition of established tumor growth in vivo. The mechanism of VES's in vivo effects may involve inhibition of tumor angiogenesis since VES inhibits VEGF gene expression.

Sentinel node biopsy for staging of aggressive digital papillary adenocarcinoma.

BACKGROUND: Aggressive digital papillary adenocarcinoma is a rare malignancy with a propensity for metastases and recurrence. The role of lymph node staging in this tumor is poorly defined. We describe the use of sentinel lymph node mapping and biopsy in staging this tumor. OBJECTIVE: To describe and discuss the use of lymphatic mapping in staging aggressive digital papillary adenocarcinoma. METHODS: Sentinel lymph node mapping and biopsy was performed after excision of an aggressive digital papillary adenocarcinoma of the toe. RESULTS: Metastatic tumor cells were absent in sentinel lymph nodes by hematoxylin and eosin staining and immunocytochemistry analysis. CONCLUSION: We describe the first reported case of staging lymph nodes in a patient with aggressive digital papillary adenocarcinoma utilizing sentinel lymph node mapping and biopsy.

Angiogenesis correlates with metastasis in melanoma.

BACKGROUND: Angiogenesis has been correlated with melanoma progression, but its role in melanoma metastasis is unclear. METHODS: To determine whether angiogenesis correlates with the presence of melanoma metastases, we compared the number of microvessels in the primary melanomas of 12 patients presenting with metastases to those of 13 patients without metastases. Patient groups were matched for gender, age, tumor depth, and histological type and anatomical location of the primary melanoma. Microvessels were stained with factor VIII antibody and counted. RESULTS: Microvessel counts were significantly greater for the metastatic than the nonmetastatic melanomas (51.63+/-14.95 vs. 24.86+/-8.415; P < .0001). One hundred percent of the metastatic melanomas had a mean microvessel count of > or = 37, whereas only 8% of the nonmetastatic melanomas had a mean microvessel count of > or = 37 (sensitivity = 1.00, specificity = .92). Interestingly, patients with lymph node metastases had significantly lower microvessel counts than did patients with distant metastases (42.00+/-3.482 vs. 58.50+/-16.40; P < .05), and significantly higher microvessel counts than did patients without metastases (42.00+/-3.482 vs. 24.86+/-8.415; P < .001). CONCLUSIONS: An increased number of microvessels in the primary tumors of patients with melanoma correlates with the simultaneous presence of metastases. This suggests that angiogenesis may be important in the process of melanoma metastasis.

Isolation and functional analysis of a Kluyveromyces lactis RAP1 homologue.

Saccharomyces cerevisiae RAP1 (Sc RAP1) is an essential protein which interacts with diverse genetic loci within the cell. RAP1 binds site-specifically to the consensus sequence, 5'-AYCYRTRCAYYW (UASRPG, where R = A or G, W = A or T, Y = C or T). In Kluyveromyces lactis (Kl) ribosomal protein-encoding genes (rp) retain functional RAP1-binding elements, suggesting the presence of a RAP1-like factor. Kl extracts display an activity capable of specifically binding to rp fragments bearing UASRPG. We subsequently isolated the Kl RAP1-encoding gene by homology to a subfragment which encodes the N terminus of the DNA-binding domain of Sc RAP1. The predicted amino acid (aa) sequence of Kl RAP1 indicates it is smaller than Sc RAP1 (666 vs. 827 aa) with the N terminus being truncated. The DNA-binding domain is virtually identical between the two RAP1 proteins, while the RIF1 domain is moderately conserved. The region between these two domains and the N-termini are highly divergent. Two potential UASRPG were identified in the 5' flanking region, suggesting an autoregulatory role for RAP1. Despite the similarities between the two proteins, KI RAP1 is unable to complement Sc rap1ts mutants, suggesting that domains essential for function in Sc are absent from the Kl protein.