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Biomedical subjects

S R Bramhall

Publications and source records attributed to S R Bramhall.

At least 19 recordsLinked to original sources
PubMed2006

Role of completion pancreatectomy as a damage control option for post-pancreatic surgical complications.

INTRODUCTION: Management of pancreatic leak and haemorrhage is complex with high mortality rates. In this study, the results of completion pancreatectomy which was performed as a last resort option were analysed. PATIENTS AND METHODS: 25 patients who had completion pancreatectomy from among 677 patients who had pancreatoduodenectomy or distal pancreatectomy over a period of 18 years were analysed in terms of the indications for completion pancreatectomy, outcome and survival data. RESULTS: Indications for completion pancreatectomy include pancreatic leak in 12 patients (48%), both bleeding and pancreatic leak in 8 (32%), and haemorrhage alone in 5 (20%) patients. 18 (72%) patients also had splenectomy. Median ITU stay was 4 and 8 days for those who survived and died post-completion pancreatectomy, respectively. 36% patients had septicaemia and 32% patients had multiple organ failure. 12 patients survived the operation with a median survival of 52 months. CONCLUSION: 25 (3.6%) patients required surgical intervention for pancreatic complications. The incidence of splenectomy was 84.6% in those who died after completion pancreatectomy compared to 58.3% of those who survived (Fisher's exact test two-sided 0.20). Despite significant morbidity and mortality, completion pancreatectomy has a role in the management of post-pancreatic surgical complications.

Adult↗
PubMed2006

Haemorrhage following pancreaticoduodenectomy: risk factors and the importance of sentinel bleed.

AIM: To document the prevalence and to evaluate the management strategies of haemorrhagic complications following pancreaticoduodenectomy (PD). METHODS: All patients who underwent PD from 1/2000 to 10/2005 and experienced at least one episode of haemorrhage during the 30 first days postoperatively were recorded. Etiology of haemorrhage, treatment strategy and mortality rate were recorded and analyzed. RESULTS: A total of 362 patients underwent PD during this period and 32 (8.8%) had haemorrhage postoperatively of whom 15 died (47% mortality rate). Primary intraluminal haemorrhage was recorded in 13 patients, primary intra-abdominal haemorrhage in 5 patients and secondary haemorrhage in 14 patients. Successful management of haemorrhage with angioembilization occurred in 2 patients in the study group. Statistical analysis revealed sepsis and sentinel bleed as risk factors for post-PD haemorrhage and pancreatic leak and sentinel bleed as risk factors for secondary haemorrhage (p < 0.05). CONCLUSIONS: Haemorrhage after PD is a life-threatening complication. Sepsis, pancreatic leak, and sentinel bleed are statistical significant factors predicting post-PD haemorrhage. Sentinel bleed is not statistically significant associated with postoperative mortality, but with the onset of secondary haemorrhage. The effectiveness of therapeutic angioembolization was not demonstrated in our study.

Adult↗
PubMed2006

Diabetic control after total pancreatectomy.

BACKGROUND: Diabetes after total pancreatectomy is commonly described as 'brittle' with most series reporting outcomes after resection for pancreatitis alone. The aim of this study was to determine glycaemic control in patients resected for benign and malignant disease. METHODS: A retrospective analysis of all patients undergoing total pancreatectomy (1989-2003) from a single institution was done. Data of diabetic control were obtained from case notes, general practitioners and telephonic consultation. Comparison was made against a matched type 1 diabetic population. RESULTS: Forty-seven patients with a median age of 59 years (range 17-85 years) and median follow-up of 50 months (range 5-136 months) were identified. Thirty-five underwent primary resection with 11 receiving completion procedures. Thirty were for malignancy (19 deceased) and 17 for benign/indeterminate histology (2 deceased). Thirty-three patients were available for detailed follow-up. There was no significant difference between median HbA(1c) of the study group and the control (8.2% versus 8.1%). The majority of patients reported diabetic control and daily performance as excellent or good. Resection for pancreatitis gave poorer subjective control (p < 0.05) than those resected for malignancy. Two patients required in-patient treatment for diabetic complications, with no deaths related to diabetes observed. CONCLUSION: Diabetes after total pancreatectomy is not necessarily associated with poor glycaemic control and in the majority results in equivalent biochemical control compared to a normal type 1 diabetic population.

Adolescent↗
PubMed2006

A tale of three spilled gall stones: one liver mass and two abscesses.

Spilled gall stone has been one of the most common complications of laparoscopic cholecystectomy. Spillage occurs in up to 40% of cases; complications related to spillage are rare and can present within weeks to years. We report 3 cases referred to a tertiary centre for management of such complications. The first patient presented with clinical and radiological findings of cyst 1 week after laparoscopic cholecystectomy. She was initially thought to have a hydatid cyst. At laparotomy it turned out to be a liver abscess with stones at the centre of the cavity. The second patient presented with recurrent episodes of fever and on investigation was found to have a sub-hepatic abscess. The third patient had similar clinical symptoms to the second patient but presented 7 years after surgery. We recommend that every attempt should be made to avoid gall-bladder perforation during dissection; if this happens every effort should be made to remove the spilled stones.

Abdominal Abscess↗
PubMed2005

Endostatin expression in a pancreatic cell line is modulated by a TNFalpha-dependent elastase.

Endostatin, an inhibitor of angiogenesis, is a 20 kDa fragment of the basement membrane protein, collagen XVIII. The formation of endostatin relies upon the action of proteases on collagen XVIII. TNFalpha, produced by activated macrophages, is a multifunctional proinflammatory cytokine with known effects on endothelial function. We postulated that TNFalpha may modulate the activities of proteases and thus regulate endostatin formation in pancreatic cells. Collagen XVIII/endostatin mRNA was expressed in one pancreatic cell line, SUIT-2, but not in BxPc-3. The 20 kDa endostatin was found in the cell-conditioned medium of SUIT-2 cells. Precursor forms only were found in the cells. Exogenous endostatin was degraded by cellular lysates of SUIT-2 cells. Elastase activity was found in cell extracts but not the cell-conditioned media of SUIT-2 cells. Incubation of SUIT-2 cells with TNFalpha increased intracellular elastase activity and also increased secretion of endostatin into the medium. We conclude that endostatin is released by SUIT-2 cells and that increases in intracellular elastase, induced by TNFalpha, are correlated with increased secretion. Endostatin is however susceptible to degradation by intracellular proteases and if tissue injury accompanies inflammation, endostatin may be degraded, allowing angiogenesis to occur.

Angiogenesis Inhibitors↗
PubMed2005

Neuroendocrine tumours of the pancreas: predictors of survival after surgical treatment.

AIMS: Neuroendocrine tumours of pancreatic and duodenal origin (NETP) are rare and we present a significant experience from a single centre. METHODS: Data was collected on 44 patients who underwent surgery between 1988 and 2002. Since 1997, data have been recorded prospectively on a dedicated database. RESULTS: Twenty-four patients had functioning tumours (16 insulinomas, 3 gastrinomas, 2 somatostatinomas, 1 vipoma, 1 glucagonoma and 1 carcinoid tumour). Nine functioning tumours and 13 non-functioning had a malignant phenotype. Twenty pancreaticoduodenectomies, 9 local excisions, 7 distal and 2 total pancreatectomies, 5 bypasses and 1 exploratory laparotomy were performed. Fourteen patients (31.8%) had surgical complications, 1 died peri-operatively (2.3%). The overall actuarial survival for resected cases was 74.4 and 42.5% at 5 and 10 years, respectively. Lymph node invasion and metastases were significant predictors of survival by univariate analysis and only the presence of metastases retained significance on multivariate analysis. CONCLUSION: Surgical resection is the only curative treatment for NETP. Resection can be safely carried out in a specialist centre and is associated with good long-term survival. The presence of metastases was a significant predictive factor for survival in patients with NEPT in this series.

Adolescent↗
PubMed2005

Surgery for hilar cholangiocarcinoma; a 10 year experience of a tertiary referral centre in the UK.

OBJECTIVE: To review the outcome of patients operated for hilar cholangiocarcinoma and analyse prognostic variables. PATIENTS AND METHODS: A prospectively collected database on patients with hilar cholangiocarcinoma, between 1992 and 2003, and relevant clinical notes were reviewed retrospectively. A total of 174 patients, 96 male, median age 63 years (27-86), were referred. Jaundice was the initial presentation in 167. RESULTS: ERCP was the initial interventional investigation at the referring centre in 150, of which only 30 were stented successfully. PTC and decompression was carried out on 120. In 17, combined PTC and ERCP were required for placement of stents. Seventy-two underwent laparotomy at which 27 had locally advanced disease. Forty-five had potentially curative resections. Extra hepatic bile duct resection was done in 14 patients of which four were R0 resections. Thirty-one had bile duct resection including partial hepatectomy with 19 R0 resections (P=0.042). Post-operative complications developed in 19 patients, and there were 4 30 day mortalities [hepatic insufficiency:/sepsis (n=3), thrombosis of the reconstructed portal vein (n=1)]. Among the patients with R0 resections, the cumulative survival rates at 1, 3, and 5 year; was 83, 58, 41%, respectively, and in those with R1 resections were 71, 24, 24%, respectively, (P=0.021). Overall survival was shorter in patients with positive perineural invasion (P=0.066: NS). There was no significant difference in survival between the node positive and negative group. Median survival of patients who underwent liver resection was longer than those with bile duct resection only (30 vs 24 months P=0.43: NS). CONCLUSIONS: ERCP was associated with a high failure rate in achieving pre-operative biliary decompression which was subsequently achieved by PTC. Clear histological margins were associated with improved survival and were better achieved by liver resection as compared to extra hepatic bile duct resection. Positive level I lymph nodes did not adversely impact survival.

Adenocarcinoma↗
PubMed2005

Endostatin expression in pancreatic tissue is modulated by elastase.

Pancreatic tumours are scirrhous, avascular tumours, suggesting that they may produce angiogenesis inhibitors that suppress the growth of the vasculature to the tumour and metastases. We have sought evidence for the angiogenesis inhibitor, endostatin, in normal and cancerous pancreatic tissue. Using Western blotting, we found mature 20 kDa endostatin in cancer tissue but not in normal tissue. Several endostatin-related peptides of higher mol wt were present in both tissues. Extracts from normal tissue were able to degrade exogenous endostatin, whereas extracts from cancer were without effect. Although the exocrine pancreas secretes inactive proenzymes of trypsin, chymotrypsin and elastase, their possible role in this degradation was examined. The trypsin/chymotrypsin inhibitor, Glycine max, did not prevent the degradation of endostatin by normal pancreatic extracts but elastatinal, a specific inhibitor of elastase, reduced the rate of degradation. Extracts of pancreatic tumours did not express any detectable elastase activity, but an elastase (Km 1.1 mM) was expressed by extracts of normal pancreas. We conclude that endostatin is present and stable in pancreatic cancer tissues, which may explain their avascular nature, but that normal pancreatic tissue expresses enzymes, including elastase, which rapidly degrade endostatin. The stability of endostatin may have implications for its therapeutic use.

Angiogenesis Inhibitors↗
PubMed2005

Surgical treatment of metastases to the pancreas.

BACKGROUND AND AIMS: Metastases to the pancreas are rare and their surgical treatment is not well reported. We present a considerable experience from a single centre analysing various prognostic factors. METHODS: Data were collected on 13 cases who underwent surgery between 1988 and 2002. Since 1997, data have been recorded prospectively on a dedicated database. Clinical and histopathological factors were reviewed. RESULTS: There were two women and 11 men with a median age of 62 years (range 40-73). There were seven cases of renal cell carcinomas, three colorectal carcinomas, two sarcomas and one lung carcinoma. A prolonged disease-free interval from primary surgery was characteristic for renal cell carcinoma cases (median = 10.8 years). The operative procedures performed included seven pancreatoduodenectomies, four total and two distal pancreatectomies. The operative mortality and morbidity was 7.7% and 46.1% respectively. The overall one- and two-year survival was 78.8% and 54% respectively. Median survival for renal cell carcinoma was 30.5 months and for non-renal cell carcinoma was 26.4 months (p = 0.76). CONCLUSIONS: Pancreatectomy should be considered for metastases to the pancreas in the absence of generalised metastatic disease. However, decision making and experience should be concentrated in centres with significant familiarity of this approach.

Adult↗
PubMed2004

Treatment of hydatid disease of the liver. Evaluation of a UK experience.

BACKGROUND: Hydatid disease of the liver though endemic in many countries, is rare in the UK. We evaluated a 16-year experience of treating hydatidosis using a management protocol combining surgery with anti-scolicidals. PATIENTS AND METHODS: There were 30 patients. 14 (47%) males, median age 41 (range 25-72) years, of whom 21 (70%) were symptomatic. Diagnosis was by serological tests and imaging. All had disease confined to the liver and received peri-operative anti-scolicidal drug therapy. RESULTS: The initial 4 (13%) patients received praziquantel combined with albendazole for 2 weeks and the following 26 (87%) patients received two cycles of albendazole 400 mg twice daily for 28 days, with a 14-day break in between. However, 2 (7%) patients could not tolerate albendazole, one due to GI side effects and the other developed deranged liver functions. These 2 patients subsequently received praziquantel for 2 weeks. All patients underwent surgery. Subtotal cystectomy was carried out on 29 (96%) patients and 1 patient required a segmentectomy. Cystobiliary communications were identified in 15 (50%) of patients which were oversewn using fine absorbable sutures. Of these, 7 had the bile ducts decompressed using a T tube, with only 1 developing a post-operative bile leak. In comparison, 8 were not drained of which 6 leaked (p = 0.03). The median post-operative hospital stay was 8 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 combined with anti-scolicidal therapy proved effective. Cystobiliary communications are common and, when identified, should result in the biliary system being drained, to avoid post-operative bile leaks.

Adult↗
PubMed2004

Favourable prognostic factors in a large UK experience of adenocarcinoma of the head of the pancreas and periampullary region.

AIMS: To present the surgical experience in a regional unit, analysing the post-operative outcome, and determining risk factors for survival after pancreaticoduodenectomy for periampullary and pancreatic head carcinoma. METHODS: Data were collected on 251 patients with pancreatic head adenocarcinoma (133), ampullary carcinomas (88) and distal common bile duct (30), between 1987 and 2002. Survival was calculated using the Kaplan-Meier method. Clinical, surgical and histopathological records were examined by univariate and multivariate analysis to identify the independent prognostic predictors of survival. RESULTS: Median actuarial survival for carcinoma of the pancreatic head, ampulla and distal bile duct were 13.4, 35.5 and 16 months, respectively; p < 0.0001. On univariate analysis for the whole series, the age < or =60, tumour of the head of the pancreas, lymph node positive, resection margin R1, poorly differentiated tumours, and portal vein invasion significantly decreased survival. On multivariate analysis, poor tumour differentiation, surgical margin, lymph node metastases, and age independently influence survival. Mortality and morbidity were 4.8 and 29.9%, respectively. CONCLUSIONS: Pancreaticoduodenectomy for pancreatic and periampullary tumours is the only therapy that may cure patients and can be performed safely in centres with significant experience.

Aged↗
PubMed2003

Liver resection for colorectal metastases.

BACKGROUND: Colorectal cancer is the second commonest malignancy in the UK. Metastases to the liver occur in greater than 50% of patients and remain the biggest determinant of outcome in these patients. Liver resection is a safe procedure that achieves good long-term survival, but surgery has traditionally been limited to select groups of patients. The improved outcome suggests that more patients could benefit from resection if more was known of what criteria are predictive of a good outcome. PATIENTS AND METHODS: A retrospective analysis was performed on all patients undergoing surgical resection of the liver for colorectal metastases between March 1989 and March 2001 in the Birmingham Liver Unit. RESULTS: During this period, 212 liver resections for colorectal cancer metastases were performed in 82 females and 130 males. The median follow-up was 16 months with an overall actuarial survival of 86% at 1 year, 54% at 3 years, and 28% at 5 years. The peri-operative mortality was 2.8%. The number and timing (metachronous or synchronous) of metastatic lesions, the gender of the patient, pathological staging of the primary lesion or surgical resection margins had no significant influence on survival. Patients with lesions less than 5 cm in size had a significantly prolonged survival compared with patients with lesions greater than 5 cm in size (P < 0.004). CONCLUSIONS: Liver resection is the only curative treatment for patients with colorectal metastases. The long-term survival reported in patients with resected colorectal metastases confined to the liver is comparable to primary surgery for solid gastrointestinal tumours. Every attempt must be made to increase the availability of liver resection to patients with hepatic metastases from colorectal cancer.

Adult↗
PubMed2002

A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.

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.

Adenocarcinoma↗
PubMed2002

Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial.

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.

Adenocarcinoma↗
PubMed2002

A 10-year experience of complex liver trauma.

BACKGROUND: Liver trauma is a relatively rare surgical emergency but mortality and morbidity rates remain significant. It is likely that surgeons outside specialist centres will have limited experience in its management; therefore best practice should be identified and a specialist approach developed. METHODS: Data collected from 52 consecutive patients over a 10-year interval were examined to identify best practice in the management of these injuries. RESULTS: The majority of injuries occurred as a result of road traffic accidents; 39 (75 per cent) of the 52 patients were stable at presentation to the referring hospital. In 36 patients (69 per cent) the liver injury was a component of multiple trauma. Ultrasonography, computed tomography or no radiological investigation was used in the referring hospital in 18 (35 per cent), 25 (48 per cent) and nine (17 per cent) patients respectively. Operative management was undertaken in the referring hospital in 26 patients (50 per cent). The overall mortality rate was 23 per cent (12 of 52 patients), and increased with increasing grade of severity. Eight of 26 patients managed surgically at the referring hospital died, compared with four of the 26 patients managed without operation (P not significant). The median time from arrival at the referring hospital to operation was 4 h for haemodynamically stable patients and 3 h for those who were haemodynamically unstable. CONCLUSION: Most patients with liver trauma can be managed conservatively. Operative management carried out in non-specialized units is associated with high mortality and morbidity rates. Abdominal injuries should raise a high index of suspicion of liver injury, and the data suggest that computed tomography of the abdomen should precede laparotomy (even in some haemodynamically unstable patients) to facilitate discussion with a specialist unit at the earliest opportunity.

Accidents, Traffic↗
PubMed2001

The use of liver grafts from donors with bacterial meningitis.

BACKGROUND: The shortage of suitable donors for transplantation is a worldwide problem. The use of cadaveric donors with bacterial meningitis may be associated with an increased risk of sepsis. We report the results of orthotopic liver transplantation (OLT) from 33 such donors between 1989 and 1999. METHODS: The hospital records of recipients from cadaveric donors with meningitis (study group) were retrospectively reviewed and compared with matched recipients from cadaveric donors dying from causes other than meningitis (recipient-matched control group). RESULTS: A total of 34 recipients underwent 21 whole, 10 reduced, and 3 split liver transplants from 33 cadaveric donor livers with bacterial meningitis. The donor meningitis pathogens were Neisseria meningitidis (n=14), Streptococcus pneumoniae (n=4), Haemophilus influenzae (n=1), Streptococcus species (n=2), and unknown (n=12). Twenty-seven patients had an elective OLT and seven patients had an emergency OLT. Adequate antimicrobial therapy before organ procurement and after transplant was administrated. The mean posttransplant follow-up was 37 months (range: 1 day-106 months). There was no difference in recipient and graft survival rates between the study and the recipient-matched groups. In the study group, there were no infectious complications caused by the meningeal pathogens. Overall patient survival rates were 79%, 76%, 72%, and 72% at 1, 6, 12, and 60 months, respectively. Graft survival was 77%, 70%, 65%, and 65% at 1, 6, 12, and 60 months, respectively. The survival rate in elective cases was significantly better than emergency cases (P<0.05). CONCLUSION: Liver transplantation from donors with bacterial meningitis is a safe procedure provided both donors and recipients receive adequate antimicrobial therapy.

Adolescent↗