The objective of this study was to evaluate the safety and efficacy of adult-to-adult living donor liver transplantation, specifically donor outcomes. A systematic review, with searches of the literature up to January 2004, was undertaken. Two hundred and fourteen studies provided information on donor outcomes. The majority of these were case series studies, although there were also studies comparing living donor liver transplantation with deceased donor liver transplantation. Both underreporting and duplicate reporting is likely to have occurred, and so caution is required in interpretation of these results. Overall reported donor mortality was 12 to 13 in about 6,000 procedures (0.2%) (117 studies). Mortality for right lobe donors to adult recipients is estimated to be 2 to 8 out of 3,800 (0.23 to 0.5%). The donor morbidity rate ranged from 0% to 100% with a median of 16% (131 studies). Biliary complications and infections were the most commonly reported donor morbidities. Nearly all donors had returned to normal function by 3 to 6 months (18 studies). In conclusion, there are small, but real, risks for living liver donors. Due to the short history of adult-to-adult living donor liver transplantation, the long-term risks for donors are unknown. Liver Transpl 12: 24 -30, 2006.

The development of Herceptin (Trazumatab) makes testing for HER2 status important for choosing optimal therapy in breast cancer. This study addresses the precision, accuracy, and reproducibility of HER2 assays. HER2 was assessed retrospectively by immunohistochemistry (IHC) with Dako 'Herceptest', by IHC with the monoclonal antibody CB11, and by fluorescence in situ hybridization (FISH, PathVysion), in a series of 216 formalin-fixed breast carcinomas including 191 for which quantitative HER2 data from radioimmunohistochemistry (Q-IHC) were available. All tests were scored independently by two observers. Positivity rates varied between Herceptest (12.6%), FISH (19.4%), and CB11 IHC (28.5%). Kappa values showed that IHC-based tests were more susceptible to inter-observer variation (kappa=0.67 and 0.74 for Herceptest and CB11, respectively) than FISH (kappa=0.973). Overall test accuracy (see the Materials and methods section) for CB11 IHC (83.8%) was lower than Herceptest (87.4%) or FISH (93.2%). FISH predicted p185 HER2 overexpression (determined by Q-IHC) better (concordance index C.Ind. 0.90) than CB11 IHC (C.Ind.=0.85) or Herceptest (C.Ind.=0.81). Of 42 cases with gene amplification by FISH, 67% were positive in the Herceptest (2+ or 3+) vs. 83% with CB11. Of 174 cases negative by FISH, 96% were negative in the Herceptest and 68% with CB11. In conclusion, FISH is the most accurate, reproducible, and precise predictor of HER2 overexpression in routine diagnostic laboratories.

Background: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1-4 status for further clarification of the differing roles for the HER family at a biological level.Methods: Seventy-eight invasive breast cancers had BrdU labelling in vivo to determine the BrdU labelling index (BLI) and the potential tumour doubling time (T pot ). Long-term clinical follow-up was available for these patients. We used immunohistochemistry to establish the HER1-4 status in 55 patients from the BrdU cohort. Results:We demonstrate a significant correlation between high BLI values and breast cancer-specific death (P = 0.0174). Low T pot times were also significantly correlated with breast cancer-specific death (P = 0.0258). However, BLI did not independently predict survival in Cox's multiple regression analysis when combined with other prognostic factors such as size, grade and nodal status. Tumours found to be positive for HER1, HER2 or HER3 had significantly (P = 0.041) higher labelling indices, with HER1 also showing significantly higher indices when considered independently (P = 0.024). Conversely, HER4 positivity was significantly correlated (P = 0.013) with low BLI values, in line with previous data associating this receptor with good prognosis tumours. Conclusions:These results support the hypothesis that HER1-3 are associated with driving tumour proliferation, whereas HER4 is involved in a non-proliferative or even protective role.

In recent years investigators have looked at the human epidermal growth factor receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancer patients, with regard to its role as a prognostic and predictive factor. Although many studies have suggested that HER2 overexpression may be associated with a poor clinical outcome, other studies have not fully supported this observation. The inconsistencies between studies may be due in part to discrepancies between different HER2 testing methods. To overcome this problem, a radioimmunohistochemical method was developed to quantitatively measure HER2 overexpression levels in breast tumor samples. The application of this method demonstrated that 85% of all breast tumor samples expressed HER2 at levels greater than normal. Of these, 23% expressed HER2 at levels between 45 and 480 times greater than normal, and this was associated with poor clinical outcome. The investigation of HER2 status as a predictor of response to therapy has also yielded many conflicting results. Overall, it appears that HER2 overexpression may correlate with resistance to hormonal therapy, sensitivity to anthracycline-based chemotherapy and resistance to CMF. With the development of targeted anti-HER2 therapies, assessment of HER2 status will be important in stratifying patients to the most appropriate treatment regimens.

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