Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m 72 ) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified.

The trends in treatment and outcome of 13,560 patients with pancreatic cancer, and in incidence of the disease, in the West Midlands health region were determined between 1957 and 1986 using data from the West Midlands Region Cancer Registry. Patients were divided into those diagnosed in the first 20 years (1957-1976, n = 7888) and the most recent 10 years (1977-1986, n = 5672). The disease was more common in men and the incidence increased up to 1970 after which it levelled off. In the 1977-1986 period a lower proportion of patients had laparotomy alone (825 (14.5 per cent) versus 1552 (19.7 per cent)), a similar proportion had bypass surgery (2010 (35.4 per cent) versus 2760 (35.0 per cent)), while a greater proportion had supportive care (2710 (47.8 per cent) versus 3368 (42.7 per cent)) but the resection rates were the same (145 (2.6 per cent) versus 208 (2.6 per cent)). The 30-day mortality rates between the two periods improved for resection (40 (27.6 per cent) versus 94 (45.2 per cent)), bypass surgery (436 (21.7 percent) versus 691 (25.0 per cent)) and laparotomy (372 (45.1 per cent) versus 873 (56.3 per cent)). The 12-month survival rate for bypass did not significantly differ during the study (14.9 per cent versus 12.4 per cent) but there was a significant improvement in the 5-year survival for resection (9.7 per cent versus 2.6 per cent, P < 0.015). The resection rates were low and 30-day mortality rates for surgery were high compared with those of other published series.

Hepatic artery thrombosis (HAT) occurs in 3-9% of all liver transplants and acute graft loss is a possible sequelae. We present our experience in the management of HAT over a 10-year period. Prospectively collected data from April 1994 to April 2004 were analyzed. There were 1,257 liver transplants, 669 males, median age 51 (16-73) years. There were 61 (4.9%) cases of HAT. Early HAT occurred in 21 (1.8%). Thirty six had graft dysfunction, 11 required a regraft, and 14 died. Positive CMV serology in the donor, cold ischemia time, duration of operation, transfusions of more than 6 units of blood, and 15 units of plasma, an aortic conduit for arterial reconstruction, Roux-en-Y biliary reconstructions, regrafts and relaparotomy were associated with HAT. At multivariate analysis, type of biliary anastomosis was the only significant factor associated with HAT. Split or reduced liver graft were not risk factors for HAT. Number of hepatic arteries requiring multiple arterial anastomosis was not a risk for HAT. HAT resulted in a reduction in overall survival post liver transplantation. The incidence of HAT was 4.9%; with 1.8% early HAT and HAT impacted on survival. Surgical technique was not an aetiological factor for HAT. In conclusion, while a Roux-en-Y biliary reconstruction was an independent risk factor for HAT, cold ischemia and operative times, the use of blood and plasma and the use of aortic conduits in arterial reconstruction were associated with HAT. Regrafts and reoperation were also identified risk factors. Liver Transpl 12: 146 -151, 2006.

The results of this study provide evidence of a dose response for marimastat in patients with advanced pancreatic cancer. The 1-year survival rate for patients receiving marimastat 25 mg was similar to that of patients receiving gemcitabine. In view of the manageable tolerability of marimastat and its ease of administration, further studies are warranted.