Jonathon Fawcett

Systematic review of the impact of volume of oesophagectomy on patient outcome

Purpose:  This systematic review aims to assess whether overall survival, mortality, morbidity, length of stay and cost of performing oesophagectomy are related to surgical volume.

Centralization and the relationship between volume and outcome in knee arthroplasty procedures

Background:  Centralization aims to reduce adverse patient outcomes by concentrating complex surgical procedures in specified hospitals.

Radical prostatectomy: a systematic review of the impact of hospital and surgeon volume on patient outcome

Background:  To assess the impact of hospital and surgeon volume on mortality, morbidity, length of hospital stay and costs of radical prostatectomy (RP).

Lymphocyte apoptosis and cell replacement in human liver allografts

Background. Apoptosis of graft-infiltrating T cells has been described after rodent liver transplantation. The aim of this study was to assess lymphocyte apoptosis in human allografts. Additionally, kinetics of leukocyte turnover were studied to determine whether apoptotic cells were likely to be of donor or recipient origin. Methods. Liver biopsy specimens (n=36) taken between days 3 and 1855 were stained with terminal deoxynucleotidyl transferase dUTP nick end-labeling and anti-CD3 to detect apoptotic lymphocytes. Renal allograft and hepatitis C biopsy specimens served as controls. Donor cell turnover was studied in sex-mismatched grafts using Y-chromosome in situ hybridization to detect recipient cells and double immunostaining for leukocyte phenotyping. Results. T-cell apoptosis was prominent in hepatic sinusoids (72% of biopsy specimens) as early as day 3. It ranged from 0% to 18.2% of CD3+ cells (mean 5.28±0.82%) and persisted for >14 days, including time points >1 year. There was no difference between biopsy specimens with or without rejection (6.34±1.14% and 4.61±1.13%, P =NS). Apoptotic cells in portal tracts were less frequent (33% of biopsy specimens) and less abundant (1.13±0.36%, P <0.0001). No lymphocyte apoptosis was seen in renal allograft biopsy specimens or hepatitis C biopsy specimens, indicating that it is a distinctive feature of the liver allograft. Persisting lymphocyte apoptosis even after donor lymphocytes had been replaced suggests that recipient lymphocyte deletion must occur. Donor Kupffer cells persisted for many months. Conclusions. Our results suggest that the sinusoidal microenvironment promotes recipient lymphocyte apoptosis, which may account for the improved outcome of liver grafts compared with other organ allografts.

A systematic review of the impact of volume of hepatic surgery on patient outcome.

Giuseppe Garcea, Stephanie O. Breukink, Nicholas E. Marlow, Guy J. Maddern, Bruce Barraclough, Neil A. Collier, Ian C. Dickinson, Jonathon Fawcett and John C. Graham

Increased mononuclear cell activation and apoptosis early after human liver transplantation is associated with a reduced frequency of acute rejection.

Experimental models of orthotopic liver transplantation (OLT) have shown that the very early events post‐OLT are critical in distinguishing immunogenic and tolerogenic reactions. In rodents, increased leukocyte apoptosis and cytokine expression have been demonstrated in tolerogenic strain combinations. Information from human OLT recipients is less abundant. The aim of this study was to determine the amount of early leukocyte activation and apoptosis following human OLT, and to correlate this with subsequent rejection status. Peripheral blood mononuclear cells (PBMC) were isolated from 76 patients undergoing OLT — on the day prior, 5 hrs after reperfusion (day 0), and 18–24 hrs post‐OLT (day 1). The mean level of apoptotic PBMCs on post OLT day 1 was higher than healthy recipients (0.9% ± 0.2 vs. 0.2% ± 0.1, p=0.013). Apoptosis was greater in nonrejecting (NR) (1.1% ± 0.3) compared with acutely‐rejecting (R) (0.3% ± 0.1, p=0.021) patients. On day 1, PBMC from NR patients had increased expression of IFN‐γ (p=0.006), IL‐10 (p=0.016), and CD40 ligand (p=0.02) compared with R. Donor cell chimerism on day 1 did not differ between the groups indicating that this was unlikely to account for increased PBMC apoptosis in the NR group. Interestingly, the level of chimerism on day 0 was significantly higher in NR (3.8% ± 0.6) compared with R (1.2% ± 0.4, p=0.004) patients and there was a close correlation between chimerism on day 0 and cytokine expression on day 1. These results imply that similar mechanisms are occurring in the human liver to promote graft acceptance as in the experimental models of liver transplantation and suggest that strategies that promote liver transplant acceptance in rodents might be applicable to humans. (Liver Transpl 2004;10:397–403.)

Liver Transplant Surgery

This chapter on the complex procedure of liver transplantation aims to provide information on complications, risks, and consequences of this somewhat broad procedure. For information on associated procedures, refer to the relevant chapter or volume.