Stage-for-stage comparison of definitive chemoradiotherapy, surgery alone and neoadjuvant chemotherapy for oesophageal carcinoma.

BACKGROUND: Definitive chemoradiotherapy (dCRT) has been proposed as an alternative therapy for selected patients with oesophageal cancer. The aim of this study was to determine the outcomes of dCRT, surgery alone, and neoadjuvant chemotherapy followed by surgery (CS) in patients with oesophageal cancer. METHODS: Consecutive patients diagnosed with oesophageal cancer and managed by a multidisciplinary team were staged by computed tomography and endoluminal ultrasonography. Those deemed unsuitable for surgery on the grounds of performance status, bulky local disease or personal choice received dCRT. The primary outcome measure was overall survival measured from date of diagnosis. RESULTS: Of 417 patients, 173 received dCRT, 126 underwent surgery alone and 118 received CS. The incidence of grade III/IV toxicity after dCRT and CS was 39.3 and 60.2 per cent respectively. Operative morbidity rates were 42.9 and 44.4 per cent after surgery alone and CS respectively. Thirty-day mortality rates were zero, 7.9 and 0.8 per cent after dCRT, surgery alone and CS respectively. Overall 2-year survival rates were 44.3, 56.2 and 42.4 per cent (P = 0.422). CONCLUSION: These findings support the need for a randomized trial of dCRT versus CS for resectable oesophageal cancer.

The EASTR Study: indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service.

This study provides data on National Blood Service (NBS) red blood cell (RBC, n = 9142), platelet (PLT, n = 4232) and fresh frozen plasma (FFP, n = 3584) recipients independently sampled by monthly quota from 29 representative hospitals over 12 months in 2001-2002. Hospitals were stratified by size according to total yearly RBC issues. Transfusion indications were chosen from diagnostic and procedural codes, and recipients grouped into Epidemiology and Survival of Transfusion Recipients Case-mix Groups (E-CMGs). The main E-CMGs were digestive [19% of RBC recipients; including 5% gastrointestinal (GI) bleeds and 3% colorectal surgery], musculoskeletal (15%; 12% hip and knee replacement), haematology (13%) and obstetrics and gynaecology (10%). Renal failure, fractured neck of femur, cardiac artery by-pass grafting (CABG) and paediatrics, each accounted for 3-4% recipients. FFP recipients: the main E-CMGs were digestive (21% of FFP recipients; including 7% GI bleeds and 3% colorectal surgery), hepatobiliary (15%; 7% liver disease and 2% liver transplant), cardiac (12%) and paediatrics (9%) The renal, paediatrics, vascular and haematology E-CMGs each had 6-7% of recipients. PLT recipients: the main E-CMGs were haematology (27% of PLT recipients; including 9% lymphoma and 8% acute leukaemia), cardiac (17%), paediatrics (13%), hepatobiliary (10%) and digestive (9%). Back-weighting gave national estimates of 433 000 RBC, 57 500 FFP and 41 500 PLT recipients/year in England and North Wales, median age 69, 64 and 59 years, respectively. Digestive and hepatobiliary indications emerged as the top reason for transfusion in RBC and FFP recipients, and was also a frequent indication in PLT recipients.

Randomized controlled trial to assess the impact of continuous glucose monitoring on HbA(1c) in insulin-treated diabetes (MITRE Study).

AIMS: To determine whether continuous glucose information provided through use of either the GlucoWatch G2 Biographer or the MiniMed continuous glucose monitoring system (CGMS) results in improved glycated haemoglobin (HbA(1c)) for insulin-treated adults with diabetes mellitus, relative to an attention control and standard care group. METHODS: Four hundred and four adults taking at least two daily insulin injections and with two consecutive HbA(1c) values > or = 7.5% were recruited to this randomized controlled trial (RCT). All were trained at baseline to use the same monitor for traditional capillary glucose testing throughout the 18-month study. The CGMS group were asked to wear the device three times during the first 3 months of the trial and on another three occasions thereafter. The GlucoWatch group wore the device a minimum of four times per month and a maximum of four times per week during the first 3 months and as desired for the remainder of the trial. Trained diabetes research nurses used downloaded data to guide therapy adjustments. Proportional reduction in HbA(1c) from baseline to 18 months was the primary outcome measure. RESULTS: Neither an intention-to-treat nor per-protocol analysis showed improvement in HbA(1c) in the device groups compared with standard care. For the intention-to-treat analysis, when the standard care group was compared with each of the other groups, this equated to differences in mean relative HbA(1c) reduction (95% confidence interval) from baseline to 18 months of 3.5% (-1.3 to 8.3; GlucoWatch), 0.7% (-4.1 to 5.5; CGMS), and -0.1% (-4.6 to 4.3; attention control). CONCLUSIONS: The additional information provided by these devices did not result in improvements in HbA(1c) in this population.

A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE).

OBJECTIVES: To evaluate whether the additional information provided by minimally invasive glucose monitors results in improved glycaemic control in people with poorly controlled insulin-requiring diabetes, and to assess the acceptability and health economic impact of the devices. DESIGN: A four-arm randomised controlled trial was undertaken. SETTING: Participants were recruited from secondary care diabetes clinics in four hospitals in England. PARTICIPANTS: 404 people aged over 18 years with insulin-treated diabetes mellitus (types 1 or 2) for at least 6 months who were receiving two or more injections of insulin daily were eligible. Participants had to have had two glycosylated haemoglobin (HbA1c) values > or = 7.5% in the last 15 months. INTERVENTIONS: Participants were randomised to one of four groups. Two groups received minimally invasive glucose monitoring devices [GlucoWatch Biographer or MiniMed Continuous Glucose Monitoring System (CGMS)]. These groups were compared with an attention control group (standard treatment with nurse feedback sessions at the same frequency as those in the device groups) and a standard control group (reflecting common practice in the clinical management of diabetes in the UK). MAIN OUTCOME MEASURES: Change in HbA1c from baseline to 3, 6, 12 and 18 months was the primary indicator of short- to long-term efficacy in this study. Perceived acceptability of the devices was assessed by use and a self-report questionnaire. A health economic analysis was also performed. RESULTS: At 18 months all groups demonstrated a decline in HbA1c levels from baseline. Mean percentage changes in HbA1c were -1.4 for the GlucoWatch group, -4.2 for the CGMS group, -5.1 for the attention control group and -4.9 for the standard care control group. At 18 months the relative percentage reduction in HbA1c in each of the intervention arms was less than that in the standard care control group. In the intention to treat analysis no significant differences were found between any of the groups at any of the assessment times. There was no evidence that the additional information provided by the devices resulted in any change in the number or nature of treatment recommendations offered by the nurses. The health economics analysis indicated no advantage in the groups who received the devices; a lower cost and higher benefit were found for the attention control arm. Assessment of device use and acceptability indicated a decline in use of both devices, which was most marked in the GlucoWatch group by 18 months (20% still using GlucoWatch versus 57% still using the CGMS). The GlucoWatch group reported more side effects, greater interference with daily activities and more difficulty in using the device than the CGMS group. CONCLUSIONS: Continuous glucose monitors do not lead to improved clinical outcomes and are not cost-effective for improving HbA1c in unselected individuals with poorly controlled insulin-requiring diabetes. On acceptability grounds the data suggest that the GlucoWatch will not be frequently used by individuals with diabetes because of the large number of side effects.

The EASTR study: a new approach to determine the reasons for transfusion in epidemiological studies.

Previous studies of blood use have used different methods to obtain and classify transfusion indications. Before undertaking a national study of transfusion recipients, a pilot study was performed over 2 months at two teaching and two district general hospitals to match information from hospital transfusion laboratories with clinical coding data from the hospital's Patients Administration System to determine the indication for transfusion in 2468 recipients. Data analysis revealed major limitations in the conventional use of primary diagnostic International Statistical Classification of Disease and Related Health Problems 10th Revision (ICD-10) or procedure Office of Population, Censuses and Surveys - Classification of Surgical Operations and Procedures - 4th Revision (OPCS-4) codes alone in allocating transfusion indications. A novel algorithm was developed, using both types of code, to select the probable indication for transfusion for each patient. A primary OPCS-4 code was selected for recipients transfused in relation to surgery (43%) and either the primary (36%) or the secondary (12%) ICD-10 code was chosen for recipients transfused for medical reasons. The remaining patients were unclassified. Selected codes were then collated into Epidemiology and Survival of Transfusion Recipients (EASTR) casemix groups (E-CMGs). The most frequent E-CMGs were haematology (15% of recipients), musculoskeletal (14%), digestive system (12%) and cardiac (10%). The haematology E-CMG includes patients with malignant and non-malignant blood disorders and recipients transfused for anaemia where no cause was listed. Recipients undergoing hip and knee replacement and coronary artery bypass grafting are within the musculoskeletal and cardiac E-CMGs. The digestive E-CMG includes recipients transfused for gastrointestinal (GI) bleeds and those undergoing GI surgery. This methodology provides a more useful means of establishing the probable indication for transfusion and arranging recipients into clinically relevant groups.

Feasibility and usefulness of self-assessment of bleeding in patients with haematological malignancies, and the association between platelet count and bleeding.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the collection of daily prospective information about bleeding outcomes in patients with thrombocytopenia, including information obtained by patient self-assessment. MATERIALS AND METHODS: Consecutive patients with haematological malignancies were enrolled in a study of bleeding data collection during the period of thrombocytopenia. A short educational session and information sheet was designed for self-assessment. Platelet counts and all transfusions were recorded daily. Bleeding scores were translated into World Health Organization (WHO) bleeding grades. RESULTS: Nineteen patients were included in the study. Four-hundred and ten days of thrombocytopenia were eligible for assessment of bleeds. Self-assessment was feasible, as defined by the total proportion of days on which self-assessment was completed (70%, 288 thrombocytopenic days). There was 86% agreement between bleeding data collected by self-assessment and by medical examination using a structured assessment form. Examples of discrepancies included the duration of petechiae/bruises and the reporting of minor bleeding. There was no evidence for an association between patients' morning platelet count and daily WHO bleeding grade. The incidences of WHO grade 1 and grade 2 bleeding on days with platelet counts < or = 10 x 10(9)/l, 11-20 x 10(9)/l, and > 20 x 10(9)/l were similar and did not reveal higher rates of bleeding at lower counts. CONCLUSIONS: Patient self-assessment can help to support comprehensive daily prospective monitoring of bleeding, specifically facilitating data collection following hospital discharge. The discrepancies between self-assessment and medical examination highlight the need to develop a validated international assessment tool. The association among platelet count, risk of bleeding and role of prophylactic platelet transfusions needs further evaluation in larger prospective trials.

Silent myocardial ischaemia and haemoglobin concentration: a randomized controlled trial of transfusion strategy in lower limb arthroplasty.

BACKGROUND AND OBJECTIVES: Red cell transfusion is commonly used in orthopaedic surgery. Evidence suggests that a restrictive transfusion strategy may be safe for most patients. However, concern has been raised over the risks of anaemia in those with ischaemic cardiac disease. Perioperative silent myocardial ischaemia (SMI) has a relatively high incidence in the elderly population undergoing elective surgery. This study used Holter monitoring to compare the effect of a restrictive and a liberal red cell transfusion strategy on the incidence of SMI in patients without signs or symptoms of ischaemic heart disease who were undergoing lower limb arthroplasty. MATERIALS AND METHODS: We performed a multicentre, controlled trial in which 260 patients undergoing elective hip and knee replacement surgery were enrolled and randomized to transfusion triggers that were either restrictive (8 g/dl) or liberal (10 g/dl). Participants were monitored with continuous ambulatory electrocardiogram (ECG) (Holter monitoring), preoperatively for 12 h and postoperatively for 72 h. The tapes were analysed for new ischaemia by technicians blinded to treatment. The total ischaemia time in minutes was divided by the recording time in hours and an ischaemic load in min/h was calculated. Haemoglobin levels were measured preoperatively, postoperatively in the recovery room, and on days one, three and five after surgery. RESULTS: The mean postoperative haemoglobin concentration was 9.87 g/dl in the restrictive group and 11.09 g/dl in the liberal group. In the restrictive group, 34% were transfused a total of 89 red cell units, and in the liberal group 43% were given a total of 119 red cell units. A postoperative episode of silent ischaemia was experienced by 21/109 (19%) patients in the restrictive group and by 26/109 (24%) patients in the liberal group [mean difference -4.6%; 95% confidence interval (CI): -15.5% to 6%, P = 0.41). There was no significant difference (P = 0.53) between the overall ischaemic load in the restrictive group (median 0 min/h, range 0-4.18) and the liberal group (median 0 min/h, range 0-19.48). In those patients who did experience postoperative SMI, the mean ischaemic load was 0.48 min/h in the restrictive group and 1.51 min/h in the liberal group (ratio 0.32, 95% CI: 0.14-0.76, P = 0.011). The median postoperative length of hospital stay in the restrictive group was 7.3 days [range 5-11; interquartile range (IQR) 6-8] compared with 7.5 days (range 5-13; IQR 7-8) in the liberal group. The numbers were not large enough to conclude equivalence. CONCLUSIONS: In patients without preoperative evidence of myocardial ischaemia undergoing elective hip and knee replacement surgery, a restrictive transfusion strategy seems unlikely to be associated with an increased incidence of SMI. A proportion of these patients experience moderate SMI, regardless of the transfusion trigger. Use of a restrictive transfusion strategy did not increase length of hospital stay, and use of this strategy would lead to a significant reduction in red cell transfusion in orthopaedic surgery. Our data did not indicate any potential for harm in employing such a strategy in patients with no prior evidence of cardiac ischaemia who were undergoing elective orthopaedic surgery.

Accuracy of platelet counting haematology analysers in severe thrombocytopenia and potential impact on platelet transfusion.

Although haematology analysers provide reliable full blood counts, they are known to be inaccurate at enumerating platelets in severe thrombocytopenia. If the thresholds for platelet transfusion, currently set at 10 x 10(9)/l, are to be further reduced, it is vital that the limitations of current analysers are fully understood. The aim of this large multicentre study was to determine the accuracy of haematology analysers in current routine practice for platelet counts below 20 x 10(9)/l. Platelet counts estimated by analysers using optical, impedance and immunological methods were compared with the International Reference Method for platelet counting. The results demonstrated variation in platelet counting between different analysers and even the same type of analyser at different sites. Optical methods for platelet counting on the XE 2100, Advia 120, Cell-Dyn 4000 and H3* were not superior to impedance methods on the XE 2100, LH750 and Pentra analysers. All analysers except one overestimated the platelet count, which would result in under transfusion of platelets. This study highlights the inaccuracies of haematology analysers in platelet counting in severe thrombocytopenia. It re-emphasizes the need for external quality control to improve analyser calibration for samples with low platelet counts, and suggests that the optimal thresholds for prophylactic platelet transfusions should be re-evaluated.

Sociology and behaviour of West African blood donors: the impact of religion on human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVES: Ghana is one of the countries of sub-Saharan Africa where the human immunodeficiency virus (HIV) prevalence in blood donors ranges between 1 and 4%. Considering the social importance of religion and the very high level of religious practice observed in Ghana, the hypothesis that these factors may play a role in containing HIV was tested. MATERIALS AND METHODS: Consenting HIV-infected candidate blood donors, and two age- and gender-matched seronegative control donors, were asked to complete a questionnaire regarding their religious and sexual behaviour. Multivariable conditional logistic regression was used. RESULTS: Irrespective of their HIV status or religion, 95% of the respondents believed that extra-marital sex was a sin, and 79% of those tempted to have an extra-marital affair considered that their religious beliefs helped them to abstain. In the multivariable models, having a formal role in church activities was associated with reduced odds of HIV [odds ratio (OR) = 0.41; 95% confidence interval (CI): 0.21-0.80]. Worshipping at the same location for more than 20 years was associated with a reduced risk (OR = 0.30; 95% CI: 0.08-1.10). In addition to other factors limiting HIV spread, such as male circumcision, relatively high level of education and an absence of armed conflicts in Ghana, the use of condoms conferred a reduced risk. CONCLUSIONS: An active role in religion, and reporting a lengthy duration of worship at the same place was beneficial. Collecting blood at places of worship with a strict behavioural code and from donors practicing in the community of their birth might improve blood safety.

Management of tuberculous constrictive pericarditis and tuberculous pericardial effusion in Transkei: results at 10 years follow-up.

BACKGROUND: Tuberculous pericarditis is common in Transkei (Eastern Cape). Two randomized trials showed benefits at two years for prednisolone in patients with constrictive pericarditis, and open drainage plus prednisolone in patients with pericardial effusion. AIM: To see whether the advantages of prednisolone and open drainage were maintained up to 10 years. DESIGN: Follow-up of randomized, double-blind, placebo-controlled trials. METHODS: All 383 patients (143 constriction, 240 effusion) received the same anti-tuberculosis chemotherapy. They were randomized to prednisolone or placebo for the first 11 weeks, and were followed-up over 10 years. Among the 240 with effusion, 122 were also randomized to immediate open surgical drainage of pericardial fluid versus pericardiocentesis as required. Adverse outcomes were: death from pericarditis, pericardiectomy, repeat pericardiocentesis, and subsequent open drainage. RESULTS: The 10-year follow-up rate was 96%. In constriction patients, adverse outcomes occurred in 19/70 (27%) prednisolone vs. 28/73 (38%) placebo (p = 0.15), deaths from pericarditis being 2 (3%) vs. 8 (11%), respectively (p = 0.098, Fisher's exact test). In effusion patients, adverse outcomes occurred in 14/27 (52%) with neither drainage nor prednisolone, vs. 4/29 (14%) drainage and prednisolone, 4/35 (11%) drainage and placebo, and 6/31 (19%) prednisolone and no drainage (p = 0.08 for interaction). Drainage eliminated the need for repeat pericardiocentesis. In the 176 with effusion and no drainage, adverse outcomes occurred in 17/88 (19%) prednisolone vs. 35/88 (40%) placebo patients (p = 0.003), with repeat pericardiocentesis 20 (23%) placebo vs. 9 (10%) prednisolone (p = 0.025). In a multivariate survival analysis (stratified by type of pericarditis), prednisolone reduced the overall death rate after adjusting for age and sex (p = 0.044), and substantially reduced the risk of death from pericarditis (p = 0.004). At 10 years, the great majority of surviving patients in all treatment groups were either fully active or out and about, even if activity was restricted. DISCUSSION: In the absence of a clear contraindication, a corticosteroid should be used in addition to antituberculosis chemotherapy in the management of patients with tuberculous pericarditis.

Severe complications of hysterectomy: the VALUE study.

OBJECTIVES: To model the determinants of serious operative and post-operative complications of hysterectomy and their potential risk factors. DESIGN: A prospective cohort of women undergoing hysterectomies for benign indications in 1994/1995, with a six-week postsurgery follow up. POPULATION AND SETTING: A total of 37,512 women from 276 NHS and 145 private hospitals in England, Wales and Northern Ireland, originally recruited to compare the outcomes of endometrial destruction with those of hysterectomy. METHODS: Gynaecologists reported hysterectomies for non-malignant indications carried out during a 12-month period beginning in October 1994 and follow up data were obtained at outpatient follow up six weeks postsurgery. Odds ratios of severe complications by indication and method, adjusting for measured intrinsic risk factors, were calculated. MAIN OUTCOME MEASURES: Severe operative and post-operative complications. RESULTS: Severe operative complications occurred in 3%. The risk decreased with age and increased with greater parity and history of serious illness. Women with symptomatic fibroids (4.4%, 95% CI 3.9-4.9) experienced more complications than women with dysfunctional uterine bleeding (3.6%, 3.2-3.8), adjusted odds ratio (OR) = 1.3 (95% CI 1.1-1.6). Laparoscopic procedures (6.1%) doubled the risk of operative complications of abdominal hysterectomy (3.6%) (adjusted OR = 1.9, 1.5-2.5). Post-operative complications occurred in around 1% of women, with a slight decrease with increasing age, and the strongest risk factor was a history of operative complications. Relative to dysfunctional uterine bleeding (1.0%), a higher risk for fibroids (1.2%) persisted after adjustments (RR = 1.5, 1.1-2.0). Both vaginal (1.2%) and laparoscopic (1.7%) techniques had significantly higher adjusted risks than abdominal operations (0.9%), RR = 1.4 (1.0-1.9) and RR = 1.6 (1.0-2.7). There were no operative deaths; 14 women died within the six-week postsurgery (a crude mortality rate of 3.8/1000, 2.5-6.4). CONCLUSIONS: Hysterectomy is a common, routine surgery with comparatively rare serious complications. However, younger women, women with more vascular pelvis, who undergo hysterectomy, especially laparoscopically assisted vaginal surgery for symptomatic fibroids, are at most risk of experiencing severe complications both operatively and post-operatively. Therefore, a less invasive alternative treatment for symptomatic fibroids could particularly benefit this group of women, while less invasive treatments for dysfunctional uterine bleeding, such as various methods of endometrial ablations or resections, would need to meet the current low levels of clinical complications in order to replace hysterectomy.

The role of prophylactic fresh frozen plasma in decreasing blood loss and correcting coagulopathy in cardiac surgery. A systematic review.

Summary Fresh frozen plasma is commonly used in cardiac surgery in an attempt to replace clotting factors and to decrease bleeding. Despite this, there has been no previous review of the available literature to support this practice. The aim of this review was to study the effect of prophylactic peri-operative transfusion of fresh frozen plasma on bleeding and coagulopathy in patients undergoing cardiac surgery. A comprehensive literature search was performed and all randomised controlled trials of the use of fresh frozen plasma in cardiac surgery were included. Six small trials were found that included a total of 363 participants with six different dose regimens of fresh frozen plasma. The overall quality of the studies was poor due to small patient numbers and lack of allocation concealment. There was no evidence that the prophylactic use of fresh frozen plasma affected peri-operative blood loss in cardiac surgery. There was some evidence that it may improve platelet count and fibrinogen concentration.

Characterization of long-term survival of syngeneic hepatocytes in rat peritoneum.

Hepatocyte transplantation is a potential therapy for both acute and chronic hepatic insufficiency and also for treatment of inborn errors of metabolism affecting the liver. The peritoneum is one site for implantation and has several advantages: cells implanted there can be easily identified and observed, and it has a relatively large capacity. Long-term survival using "pure" hepatocytes in the peritoneum have been disappointing. We hypothesized that cotransplantation of hepatocytes with nonparenchymal cells would help maintain differentiated hepatocyte function. Rat liver cells transplanted intraperitoneally into August rats were sacrificed at 7 days, 1, 3, 6, 9, and 12 months and analyzed for presence, basal proliferation, and functionality of hepatocytes. To demonstrate that ectopic hepatocytes remained susceptible to exogenous growth factors affecting cell proliferation, rats 9 and 12 months after transplantation were stimulated with tri-iodothyronine and KGF. Hepatocytes were identified 7 days to >12 months, by H&E and immunohistochemically, as ectopic islands in the omental fat. Functionality was confirmed by glycogen deposition. Basal proliferation in 7-day rats was 28.0 +/- 10/1000 hepatocytes in ectopic islands (cf. 5.70 +/- 2.7/1000 in recipient liver). Proliferation in ectopic islands was greater than host liver. Growth factor-stimulated proliferation in ectopic islands induced a 70-fold increase in DNA synthesis. In conclusion, hepatocytes transplanted with nonparenchymal cells survive, proliferate, and function in the peritoneum of normal rats, and respond to exogenous growth stimuli. Their survival and proliferation in the presence of a normal functioning liver has implications for the potential use of the peritoneal site clinically for supplementation of liver function in metabolic disorders.

Barcode technology: its role in increasing the safety of blood transfusion.

BACKGROUND: Incorrect blood component transfusion is the most frequent serious incident associated with transfusion. Errors responsible for these incidents frequently involve patient misidentification. STUDY DESIGN AND METHODS: This study evaluated a barcode patient identification system involving hand-held computers for blood sample collection for compatibility testing and the administration of blood. Audit of practice was carried out before and after its introduction. RESULTS: The baseline audit revealed poor practice, particularly in patient identification. Significant improvements were found in the procedure for the administration of blood following the introduction of barcode patient identification, including an improvement from 11.8 to 100 percent in the correct verbal identification of patients (p

Characterization of Long-Term Survival of Syngeneic Hepatocytes in Rat Peritoneum.

Hepatocyte transplantation is a potential therapy for both acute and chronic hepatic insufficiency and also for treatment of inborn errors of metabolism affecting the liver. The peritoneum is one site for implantation and has several advantages: cells implanted there can be easily identified and observed, and it has a relatively large capacity. Long-term survival using "pure" hepatocytes in the peritoneum have been disappointing. We hypothesized that cotransplantation of hepatocytes with nonparenchymal cells would help maintain differentiated hepatocyte function. Rat liver cells transplanted intraperitoneally into August rats were sacrificed at 7 days, 1, 3, 6, 9, and 12 months and analyzed for presence, basal proliferation, and functionality of hepatocytes. To demonstrate that ectopic hepatocytes remained susceptible to exogenous growth factors affecting cell proliferation, rats 9 and 12 months after transplantation were stimulated with tri-iodothyronine and KGF. Hepatocytes were identified 7 days to >12 months, by H&E and immunohistochemically, as ectopic islands in the omental fat. Functionality was confirmed by glycogen deposition. Basal proliferation in 7-day rats was 28.0 ± 10/1000 hepatocytes in ectopic islands (cf. 5.70 ± 2.7/1000 in recipient liver). Proliferation in ectopic islands was greater than host liver. Growth factor-stimulated proliferation in ectopic islands induced a 70-fold increase in DNA synthesis. In conclusion, hepatocytes transplanted with nonparenchymal cells survive, proliferate, and function in the peritoneum of normal rats, and respond to exogenous growth stimuli. Their survival and proliferation in the presence of a normal functioning liver has implications for the potential use of the peritoneal site clinically for supplementation of liver function in metabolic disorders.

The VALUE national hysterectomy study: description of the patients and their surgery.

OBJECTIVES: To describe hysterectomies practised in 1994 and 1995: the patients, their surgery and short term outcomes. DESIGN: One of two large cohorts, with prospective follow up, recruited to compare the outcomes of endometrial destruction with those of hysterectomy. SETTING: England, Wales and Northern Ireland. POPULATION: All women who had hysterectomies for non-malignant indications carried out during a 12-month period. METHODS: Gynaecologists in NHS and independent hospitals were asked to report cases. Follow up data were obtained at outpatient follow up approximately six weeks post-surgery. MAIN OUTCOME MEASURES: Indication for surgery, method of hysterectomy, ovarian status post-surgery, surgical complications. RESULTS: 37,298 cases were reported which is estimated to reflect about 45% of hysterectomies performed during the period studied. The median age was 45 years, and the most common indication for surgery was dysfunctional uterine bleeding (46%). Most hysterectomies were carried out by consultants (55%). The proportions of women having abdominal, vaginal or laparoscopically-assisted hysterectomy were 67%, 30% and 3%, respectively. Forty-three percent of women had no ovaries conserved after surgery. The median length of stay was five days. The overall operative complication rate was 3.5%, and highest for the laparoscopic techniques. The overall post-operative complication rate was 9%. One percent of these was regarded as severe, with the highest rate for severe in the laparoscopic group (2%). There were no operative deaths; 14 deaths were reported within the six-week post-operative period: a crude mortality rate soon after surgery of 0.38 per thousand (95% CI 0.25-0.64). CONCLUSIONS: This large study describes women who undergo hysterectomy in the UK, and presents results on early complications associated with the surgery. Operative complications occurred in one in 30 women, and post-operative complications in at least one in 10. Laparoscopic techniques tend to be associated with higher complication rates than other methods.