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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(-2)) 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 The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity.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. [ABSTRACT FROM AUTHOR]

This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98-1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03-1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00-2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16-2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07-1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted. [ABSTRACT FROM AUTHOR]

Aims: In view of its rarity in the UK, problems with making a diagnosis and poor prognosis if left untreated, reported series of the surgical management of gall bladder carcinoma are uncommon and debate remains whether curative resection of locally advanced disease (> stage II) is appropriate. As a tertiary referral hepato-biliary unit we report a 10 year series with the aim of demonstrating the benefits of attempted surgical resection. Methods: All 47 patients seen at the QE liver unit Birmingham between 1991 and 2002 with a presumptive diagnosis of gall bladder carcinoma were identified and the data for these patients then extracted from our prospectively collected database. Parameters examined included demographics, clinical history including previous operations, pathology, peri-operative course including complications, and outcome. Kaplan-Meier survival curves were established for stage II, III and IV disease (see figure). Results: 15 patients referred were suitable for curative resection of whom 10 had undergone previous cholecystectomy elsewhere. Procedures performed included completion cholecystectomies, extra-hepatic biliary resection + reconstruction (4), wedge resection of gall bladder bed (7) and one right hemi-hepatectomy with biliary resection. Mean overall survival, including curative and non-curative procedures, was 35 ± 14·28 months for stage II disease, 26 ± 7·2 months for stage III and 8 ± 1·68 for stage IV months (AJCC staging system). Conclusion: Survival according to the stage of disease for all patients demonstrated significant differences (P < 0·0089). Attempted curative surgical resection for stage II and Ill disease is worthwhile as suggested by our results. [ABSTRACT FROM AUTHOR]

Background: Adenoma and focal nodular hyperplasia (FNH) are rare hepatocellular tumors. Resection of adenoma is recommended because of the risk of malignant change and rupture with hemorrhage, however as FNHs are believed to remain asymptomatic, their resection is not indicated. Aim: To review the pathology of benign hepatocellular tumors presenting with rupture and assess the role of delayed surgical intervention in their management. Methods: Data for patients who presented with benign hepatocellular tumors between January 1995 and October 2002 were obtained. Only patients presenting with spontaneous rupture of tumors were studied. Results: 37 patients with benign hepatocellular tumors (adenoma: 17, FNH: 18, others: 2) were managed during this period. 8 females and 2 males presented with spontaneous rupture of tumors. 6 females were on oral contraceptives (OCP) when they bled. 6 were operated on during the same admission. 3 who remained hemodynamically stable, later underwent elective resection. Surgical resection varied from segmental resection to extended hemi-hepatectomy. There was no post-operative mortality. Surgical resection was facilitated following resolution of sub-capsular haematoma in elective resections. One patient who had multiple lesions in both lobes of liver was considered inoperable and advised to avoid the OCP and has remained well. Histology of the resected lesions showed: adenoma (7), nodular regenerative hyperplasia (1) and FNH (1). Conclusions: Hepatic adenoma is the most common benign hepatocellular turnout to present with spontaneous rupture and bleeding, however FNH may also rupture. There is a role for delayed surgical resection of bleeding tumour in a hemodynamically stable patient. [ABSTRACT FROM AUTHOR]

Background: GIST are rare tumors often presenting with advanced disease requiring extensive surgical resection. The benefits of surgery in improving survival remain unknown and alternative drug therapy has shown promising results. We present the outcome of patients from a tertiary center. Methods: 31 patients (15 M, 16 F: ages 16-82 yr, mean 59·7) with GIST were referred between January 1992 and November 2002 for surgery. Patients treated were those with advanced primaries (considered inoperable by referring surgeons) or those with metastases following primary resection elsewhere. Results: 18 were referred with primary lesions. 13 patients underwent complete resection including partial gastrectomy (4), partial gastrectomy and distal pancreatectomy (2), pylorus preserving pancreatico-duodenectomy (2), duodenal resection (3) and retroperitoneal mass excision (2). 3 patients had palliative resection and 2 were deemed unsuitable for any form of resection. Median follow-up of these patients was 23 months. 3 yr and 5 yr survival following complete resection were 86% and 57%. Longest survival following palliative resection was 15 months. 13 were referred for management of metastases, 2 of which were inoperable. 9 of the 10 patients with hepatic metastases underwent hepatic resection. One of these underwent liver transplantation (LT) for a massive central metastases. Median follow-up for those with metastatic lesions was 19 months. Only one survived more than 4 yrs (post LT), and is receiving Glivec for skeletal metastasis. Conclusions: Complete resection of primary GIST leads to prolonged survival in the majority of patients whereas resection of metastatic disease has limited application. The use of Glivec as neoadjuvant or adjuvant therapy warrants further study. [ABSTRACT FROM AUTHOR]

Aims: The incidence of bile duct injuries following laparoscopic cholecystectomy is approximately 0·5%. The management of such injuries at a tertiary referral center in the UK, with particular emphasis on early repair, is reviewed, including an outreach service, which provides immediate tertiary consultant surgical expertise, allowing immediate repair of bile duct injuries detected on-table at the referring hospital. Methods: Prospectively collected data, obtained from the Liver Unit database on bile duct injuries following laparoscopic cholecystectomy between 1991 to 2002 were analysed. Results: Total of 112 elective cases with a median follow up of 55 months were analysed. Median time or referral was two weeks. In 23 (20%) cases, the injury was recognized on table. A liver surgeon attended the referring hospital in 8 (7%) for immediate on-table repair. 33 patients had attempted repair prior to referral of which 20 required further surgery. After referral 15 (13%) were managed conservatively, 6 (5%) with ERCP and stenting, 32 (29%) with 1 interventional radiology and 59 (53%) required surgery. Commonest injury was type E2 (36%) Surgical procedures included, biliary reconstruction in 45, main hepaticojejunostomy in 31, bilateral or segmental hepaticojejunostomy in 10, re-do hepaticojejunostomy in 4, right hemihepatectomy in 3. Mortality was seen in 5 (4%), recurrent cholangitis in 9 (8%), biliary cirrhosis requiring transplantation in 1 (0·8%). Conclusions: Early recognition and referral to specialized liver units results in better outcome of bile duct injuries. Early repair by a liver surgeon has the potential for reducing long term morbidity associated with late recognition of bile duct injuries. [ABSTRACT FROM AUTHOR]

Aims: Hydatid disease of the liver though endemic in many countries, is rare in the UK. We evaluated a 16 year experience of treating hydatidosis and propose a management protocol. Methods: There were 30 patients. 14 (47%) males, median age 41 (range 25-72) years, 21 (70%) were symptomatic. Diagnosis was by serological tests and imaging. All had disease confined to the liver and received pre-operative drug therapy. Results: Twenty six (87%) patients received two cycles of albendazole 400 mg twice daily for 28 days, with a 14 day break in between. Four (13%) patients received Praziquantel at 50 mg/Kg/day, for two weeks. All patients underwent surgery. Subtotal cystectomy was carried out on 29 (96%) of patients one patient required a segmentectomy. Cystobiliary communications were identified in 15 (50%) of patients which were over sewn using fine absorbable sutures. Of these, seven had the bile ducts decompressed using a drain, with only one developing a post operative bile leak. In comparison, eight were not drained of which six leaked (P = 0·03). The median post operative hospital stay was eight days (range 5-24). Patients who developed post operative bile leaks however, needed prolonged abdominal drainage for a median of 21 days (range 18-24). Two (7%) patients developed histologically proven recurrent disease. The median follow up was 56 months (range 3-87). Conclusion: Surgery should be carried out after adequate drug therapy. Cystobiliary communications are common and when identified, should result in the biliary system being drained, to avoid post operative bile leaks. [ABSTRACT FROM AUTHOR]

Aims: It is unclear whether there is an improvement in surgical outcome for patients that undergo preoperative ERCP. We therefore sought to establish if the use of preoperative ERCP for biliary decompression is associated with an alteration in bile bacteriology and highlight the potential morbidity. Methods: A retrospective analysis was performed of 206 patients that had undergone HPB resection in our unit. The use of preoperative ERCP was established and a microbiological comparison made between those cases that underwent surgery alone and those that underwent preoperative ERCP with or without stent placement. Results: Of the 206 patients 89 had ERCP prior to surgery and 117 had surgery only. The incidence of bacteremia and fungaemia was significantly higher in the ERCP with stent group by comparison to those who had only surgery (P < 0.001). The most common organisms cultured for the all groups were coliforms and enterococcus, with an equal incidence of candida in those undergoing ERCP. Conclusion: ERCP for preoperative drainage of obstructed biliary systems is associated with a high incidence of bile bacteremia and fungal colonization. ERCP should be reserved for those patients with cholangitis preoperatively and should not be used routinely until thorough staging has been completed. [ABSTRACT FROM AUTHOR]

Aims: To show that most liver trauma can be managed conservatively and that early abdominal CT reduces the frequency of operative treatment in nonspecialized centres which carries a high mortality. Methods: We retrospectively analysed data from 52 consecutive patients referred to the Queen Elizabeth Hospital, Birmingham over a 10-year period to identify best practice in the management of these injuries. Results: The majority of injuries occurred as a result of road traffic accidents. Seventy-five per cent of the patients were stable at presentation to the referring hospital. In 70 per cent of the patients, the liver injury was a component of multiple trauma. USS, CT and no radiological investigation were used in the referring hospital in 35, 48 and 17 per cent, respectively. Operative management was undertaken in the referring hospital in 50 per cent of patients. The overall mortality in the series was 21 per cent and increased with increasing grade of severity. The mortality in patients managed operatively at the referring hospital was 31 per cent and in those managed conservatively was 15 per cent (P = ns). The median time from arrival to surgery in the referring hospital was 4 h in haemodynamically stable patients and 3 h in haemodynamically unstable patients. Conclusion: Our data suggests that the majority of cases of liver trauma may be managed conservatively and that operative management in nonspecialized units carries high mortality and morbidity. Abdominal injuries should raise a high index of suspicion of liver injury, and abdominal CT should precede laparotomy (even in some haemodynamically unstable patients) to facilitate early discussion with a specialist centre. [ABSTRACT FROM AUTHOR]