Randomized clinical trial of laparoscopic versus open donor nephrectomy.

BACKGROUND: This randomized controlled trial was designed to determine the safety and efficacy of laparoscopic donor nephrectomy (LDN) in comparison with short-incision open donor nephrectomy (ODN). METHODS: Eighty-four live kidney donors were randomized in a 2 : 1 ratio to LDN (56 patients) or short-incision ODN without rib resection (28). Primary endpoints were pain relief and duration of inpatient stay. RESULTS: There was no donor death or allograft thrombosis in either group. The first warm ischaemic time median (range) 4 (2-7) versus 2 (1-5) min; P = 0.001) and the duration of operation (160 (110-250) versus 150 (90-200); P = 0.004) were longer for LDN. LDN led to a reduction in parenteral morphine requirement 59 (6-136) versus 90 (35-312) mg; P = 0.001) and hospital stay (4 (2-6) versus 6 (2-9) days; P = 0.001), and earlier return to employment (42 (14-84) versus 66.5 (14-112) days; P = 0.004). Postoperative respiratory function was improved after LDN. There were more postoperative complications per donor in the ODN group (0.6(0.7) versus 0.3(0.5); P = 0.033). At a median follow-up of 74 months, there were no differences in renal function or allograft survival between the groups. CONCLUSION: LDN removes some of the disincentives to live donation without compromising the outcome of the recipient transplant.

Case-matched comparison of long-term results of non-heart beating and heart-beating donor renal transplants.

BACKGROUND: Function and survival of non-heart-beating donor (NHBD) renal transplants have been shown to be comparable to those from heart-beating donors (HBDs) up to 10 years after transplantation. However, there are few data on outcome after 10 years, particularly from uncontrolled NHBD donors. METHODS: All NHBD renal transplants (predominantly uncontrolled) performed between April 1992 and January 2002 were retrospectively matched with HBD renal transplants performed over the same period. RESULTS: Some 112 NHBD renal transplants were compared with 164 HBD renal transplants. Delayed graft function was significantly higher in the NHBD group (83.9 versus 22.0 per cent respectively; P < 0.001). Primary non-function rates were similar (5.4 versus 1.8 per cent respectively; P = 0.164). Overall serum creatinine was significantly higher in NHBDs (P < 0.001). Median graft and patient survival was 126 months for NHBD and 159 months for HBD kidneys. Death-censored graft survival at 1, 5, 10 and 15 years was respectively 91.8, 77.5, 61.0 and 44.2 per cent for NHBD, and 91.1, 86.3, 71.7 and 58.5 per cent for HBD kidneys (P = 0.108). CONCLUSION: Despite increased delayed graft function rates and serum creatinine levels, the long-term survival of NHBD renal transplants was similar to those from HBDs. However, there was a trend to poorer function and survival from 10 years after transplant.

Large-scale purification of human islets utilizing discontinuous albumin gradient on IBM 2991 cell separator.

A new method is described for the large-scale purification of human pancreatic islets with a discontinuous gradient of bovine serum albumin formed on an IBM 2991 cell separator. Fifteen human pancreases were processed, and after density-gradient centrifugation, a mean of 2643 islets/ml pancreatic digest were recovered with a mean purity of 63% and contained in 430 microliter mean vol. Viability of gradient-isolated islets was compared with that of non-density-gradient islets (handpicked) and showed no difference in function. This technique allows isolation of intact, viable human islets of Langerhans of sufficient purity for potential human transplantation.

A case-control comparison of the results of renal transplantation from heart-beating and non-heart-beating donors.

INTRODUCTION: The decline in heart-beating brainstem dead organ donors has necessitated the search for other organ sources. In the field of renal transplantation one alternative source currently available, but little used, is that of kidneys from non-heart-beating donors (NHBD). Reticence to use NHBD kidneys is in part due to concerns over the effect that warm ischemic may have subsequent graft function. Presented here are the results of the NHBD renal transplants at the Leicester transplant unit, and compared with matched heart-beating donor transplants as a case control analysis. METHODS: In order to analyze any differences in graft performance between the two organ sources, the confounding effect of other variables known to influence the outcome of renal transplantation was minimized by matching NHBD and HBD transplants for the following criteria: donor age and sex, first or re-transplant, anastomosis and cold times, tissue match and PRA sensitisation. Transplant performance was assessed primarily by graft survival, the statistical evaluation of which was by log rank analysis of Kaplan-Meier curves. RESULTS: 72 NHBD and 192 HBD transplants were performed over an eight year period. Of the 192 HBD transplants, 105 matched one or more of the NHBD by the criteria outlined above, and thus constituted the control group for comparison. There was no significant difference in overall graft survival between the two groups. The 5 year survival for the NHBD was 73% compared with 65% for HBD kidneys. When death with a functioning graft is treated as censored data, then these figures become 75% and 81% respectively, again without statistical significance. CONCLUSION: NHBD kidneys are a valuable additional source of organs for transplantation, with long-term survival, comparable to transplants from HBD.

The importance of E-selectin as a marker for renal transplant rejection.

Vascular endothelial cells express membrane bound adhesion molecules which play a direct role in the localization and subsequent movement of leucocytes from the blood into sites of inflammation. E-Selectin is a cytokine induced adhesion molecule, known to be expressed by endothelial cells in inflammatory conditions, which binds to various leucocyte subpopulations. In a prospective study we have investigated the expression and distribution of E-selectin on renal allograft needle biopsies taken from 16 pretransplant kidneys and 119 post-transplant kidneys. Post-transplant biopsies were taken at times of graft dysfunction and at times of normal graft function. Formal histology was also performed and assessed independently. E-Selectin was found predominantly on the intertubular endothelium and on the endothelium of larger vessels. E-Selectin was present, at low intensity, in some pretransplant biopsies and also some post-transplant biopsies which were reported histologically as normal. In post-transplant biopsies taken for dysfunction E-selectin was present in the majority of cases. Expression was strong in biopsies showing acute cellular rejection and this was associated with a CD4 positive cellular infiltrate. Biopsies showing other causes of dysfunction, in particular acute tubular necrosis, also were E-selectin and CD4 positive with lower intensity than those with acute cellular rejection. These results suggest that E-selectin is a good marker for endothelial activation in renal transplant biopsies. Its presence in histologically apparently normal biopsies suggests that its in vivo kinetics may differ from previously reported in vitro kinetics. E-Selectin may be a potential target for therapeutic intervention.

Lack of correlation of soluble E-selectin level with renal transplant rejection.

E-Selectin is a 115-kDa cell surface glycoprotein transiently expressed on vascular endothelium in response to interleukin-1 and tumour necrosis factor-alpha with a peak in expression at four hours. Its distribution in transplant biopsies has been associated with inflammatory events such as allograft rejection. Recently, a soluble isoform of E-selectin has been detected in the culture medium of cytokine activated endothelial cells by an ELISA method. In this study soluble E-selectin levels in renal allograft recipients were compared with the incidence of rejection, acute tubular necrosis (ATN), cyclosporin A (CyA) toxicity, and use of orthoclone OKT3 (muromonab-CD3) to establish whether early endothelial activation and inflammatory damage could be detected. The mean soluble E-selectin level in normal volunteers was 89 ng/ml serum compared to 120 ng/ml for a group of chronic renal failure patients. Soluble E-selectin levels declined upon transplantation but this was not significant, nor was the difference in samples from patients experiencing rejection, ATN or CyA toxicity. A dramatic and sustained rise in soluble E-selectin levels was found within 24 hours of the first dose of OKT3 treatment. This study shows that soluble E-selectin does not provide early unequivocal indication of pathological sequelae in renal transplantation, although extensive endothelial activation can be demonstrated with OKT3 treatment.

Selection criteria for preoperative endoscopic retrograde cholangiopancreatography in the laparoscopic era.

BACKGROUND: Indicators for cholangiography were originally designed to select patients at risk for common bile duct (CBD) stones for intraoperative cholangiography. OBJECTIVE: To refine these criteria to apply to the much more invasive procedure of preoperative endoscopic retrograde cholangiopancreatography (ERCP). DESIGN: Retrospective review of selection criteria for ERCP in consecutive patients referred over 18 months following the introduction of laparoscopic cholecystectomy. SETTING: Two ERCP units in adjacent teaching hospitals. PATIENTS: Three hundred seventeen patients with gallstones and in situ gallbladders. INTERVENTION: Common bile duct imaging at ERCP. MAIN OUTCOME MEASURES: Abnormalities justifying ERCP. RESULTS: Abnormalities justifying ERCP were found in 66% of patients. This group differed significantly from those with normal ducts, with more being referred with abnormal results of all liver function tests (P < .001), jaundice (P < = .001), a dilated CBD on ultrasound (P < .001), or CBD stones on ultrasound (P < .001). On the other hand, patients with normal ducts were significantly more likely to have been referred with pancreatitis (P = .003) or elevated results of individual liver function tests (P < .001). A logistic regression model using age, presence of jaundice at ERCP, levels of alkaline phosphatase and albumin, and ultrasonography showing dilated ducts or visible CBD stones was found to have a specificity of 75% and a sensitivity of 89%. Past pancreatitis or elevated results of individual liver function tests were not predictive factors. CONCLUSION: The use of such a model rather than individual criteria would improve the selection of patients for preoperative ERCP, optimizing its role in the laparoscopic era.

Endoscopic-assisted intrathoracic oesophagogastrostomy without thoracotomy for tumours of the lower oesophagus and cardia.

AIMS: This study aimed to evaluate the efficacy of a novel technique enabling a trans-hiatal oesophagectomy with intrathoracic anastomosis under direct vision, without thoracotomy. METHODS: Trans-hiatal dissection of the oesophagus was performed using direct and laparoscopic visualization. The oesophagus was transected above the tumour with a linear endo-GIA-2 60 mum stapler. The stomach was transected and a gastric tube fashioned. The anvil of an appropriately sized CEEA circular stapler was modified enabling it to flatten. It was attached to a novel delivery system introduced under direct vision along a guidewire into the stapled oesophagus. The anvil was realigned to its original position in the distal oesophagus, docked with the body of the stapler and an intrathoracic anastomosis performed. RESULTS: Ten patients (female n=3, male n=7) aged from 39--77 years (mean age 65 years), ASA 2--3 with distal third tumours were treated. Duration of procedure ranged from 2--5 hours (mean 4 hours). One patient suffered a post-operative chest infection and an anastomotic leak treated successfully with a self-expanding metal stent. Hospital stay ranged from 6--28 days (mean 17 days). There was no mortality. CONCLUSION: This technique allows a safe intrathoracic anastomosis to be performed trans-hiatally under direct vision, avoiding the need for thoracotomy in patients with high comorbidity.

Anti-CD3 enhancement of cellular cytotoxicity in cancer patients treated with interleukin-2.

Anti-CD3 monoclonal antibody was found to enhance non-MHC restricted cellular cytotoxicity in vitro in the peripheral blood mononuclear cells from normal healthy individuals. This effect was dose dependent (maximal at 0.11 micrograms/ml) and was complete within 30 minutes. Peripheral blood mononuclear cells from 4 out of 8 cancer patients treated with Interleukin-2 were deficient in their ability to respond to anti-CD3 in vitro. In contrast, peripheral blood mononuclear cells from cancer patients who subsequently displayed a tumour response to Interleukin-2, were able to respond to anti-CD3 by enhanced non-MHC restricted cellular cytotoxicity. This study demonstrates the importance of CD3+ lymphocytes in the generation of antitumour activity following in vivo Interleukin-2 administration and the ability of CD3+ve lymphocytes to respond to anti-CD3 in vitro may indicate those patients who would benefit from Interleukin-2 therapy.

Changes in biochemical laboratory investigation in patients treated with constant infusion recombinant interleukin-2.

Eight patients with metastatic hypernephroma were treated with constant infusion recombinant Interleukin-2 (rIL-2), changes in renal and hepatic function and protein levels were monitored during 2 cycles of treatment. The rIL-2 infusion caused a reversible fall in ures and a non-reversible rise in creatinine. Liver function tests (bilirubin, ALT, ALP and GGT) rose during rIL-2 treatment and had returned to pretreatment levels 3 weeks after the last day of rIL-2. There was also a reversible fall in serum protein levels during rIL-2 infusion. Although constant infusion rIL-2 ameliorated much of the severe toxicities usually seen with high-dose bolus rIL-2, the non-reversible rise in serum creatinine levels is not a previously reported feature of rIL-2 therapy.

Evaluation of the safety of recombinant interleukin-2 (rIL-2) and rIL-2 plus 5-fluorouracil (5-FU) in the adjuvant treatment of gastric cancer patients.

Eight patients received either recombinant Interleukin-2 (rIL-2) alone or rIL-2 plus 5-Fluorouracil (5-FU) by constant infusion after undergoing potentially curative surgery for gastric cancer. rIL-2, given at a dose of 18 x 10(6) IU/m2/24 hours, was safely tolerated and only two episodes of WHO grade 3 toxicities occurred, both of which promptly responded to treatment and temporary interruptions of rIL-2 infusions. 5-FU infusions given at 12.5 mg/kg/24 hours did not alter the rebound lymphocytosis seen after completion of rIL-2 infusions. We conclude that the administration of rIL-2 and rIL-2 plus 5-FU to cancer patients recovering from major surgery is safe and well tolerated.

Combined abdominal hernia repair and continuous ambulatory peritoneal dialysis (CAPD) catheter insertion.

Out of a series of 290 surgically inserted continuous ambulatory peritoneal dialysis (CAPD) catheters, 19 patients had 24 abdominal hernias repaired at the same time as CAPD catheter insertion. All catheters were used immediately after our normal postoperative break in protocol. There were no fluid leaks from the hernia repair site but 3 catheters failed due to complications unrelated to the hernia repair. CAPD technique survival was not adversely affected in the hernia repair group.

The role of omentectomy in continuous ambulatory peritoneal dialysis.

Long-term survival of the peritoneal catheter is essential for successful CAPD. In our unit, all CAPD catheters are now placed by an open surgical technique, which in some cases has included performing a partial omentectomy. The aim of this study was to assess the influence of omentectomy on CAPD catheter survival. Three hundred consecutive CAPD catheters inserted over a 5-year period were analyzed. Omentectomy was performed in 113 cases (38%). Data relating to a number of potentially significant risk/benefit factors were analyzed using multiple regression analysis (proportional hazards method of Cox). Performing a partial omentectomy at the time of catheter insertion was found to significantly improve CAPD catheter survival (p = 0.0002).

An improved method for oesophageal intubation.

The authors describe a method of inserting an Atkinson tube using a flexible upper gastrointestinal endoscope which does not require the use of X-ray screening. A retrospective review of 50 patients intubated by this technique has been undertaken and the results presented. Of the lesions, 40% were squamous cell carcinoma and 40% adenocarcinoma, with 84% being situated in the lower third of the oesophagus; 94% of patients only required one intubation. The two major complications of the procedure are tube displacement and oesophageal leak; a tube displacement rate of 13% was recorded, comparable with other series. Eleven patients (20.8%) were found to have an oesophageal leak, but this resulted in death in only three patients (6%). The reasons for these figures are explained. An operative mortality rate of 12% is comparable with series using other methods. The authors conclude that this method of intubation is as safe as Atkinson's original method but has the advantage that X-ray screening is not required.

A relationship between perioperative blood transfusion and recurrence of carcinoma of the sigmoid colon following potentially curative surgery.

Preoperative blood transfusions are used to improve graft survival in renal transplantation. If such an immunomodulating effect occurred in cancer surgery perioperative blood transfusion may be detrimental to patient outcome. A retrospective study of 68 patients undergoing potentially curative surgery for adenocarcinoma of the sigmoid colon, over a 10 year period was performed. Thirty-three patients (49%) had a perioperative blood transfusion of which two-thirds received either one or two units. Transfused patients had a poorer prognosis compared to non-transfused patients (0.28 and 0.53 five year product limit recurrence free fractions respectively; P less than 0.01 on generalised Savege test of entire recurrence free curves). Perioperative transfusion was the most sensitive prognostic indicator of recurrence on Cox proportional hazards regression analysis (relative risk 2.6; P less than 0.01, after adjustment for histological stage). Although a causal relationship is not proven, prospective work is urgently needed.

Laparoscopic cholecystectomy in Leicester: an audit of 555 patients.

Laparoscopic techniques have revolutionised the surgical approach to cholecystectomy, even though there have been no published randomised controlled trials to demonstrate the safety of this approach. We present an audit of 555 patients offered laparoscopic cholecystectomy. In all, 54 patients (9.7%) were converted to an open procedure. Peroperative cholangiography (POC) was attempted in 190 cases (34.2%) and achieved in 141 (25.4%). Major complications occurred in 26 cases (4.7%) including 5 (0.9%) deaths, two of whom had major pre-existing morbidity. There was one common bile duct (CBD) injury (0.18%). There were 30 patients (5.4%) found to have CBD stones, 27 of which were cleared at ERCP, and three converted to open exploration. Cholecystectomy by any route is a major operation and we conclude that careful case selection remains imperative. However, morbidity is favourable compared with open cholecystectomy, and comparable with other reports using the laparoscopic technique. Our experience of CBD injury (0.18%) is also acceptable compared with the risk of injury during open cholecystectomy. There were 312 patients (56.2%) who did not undergo perioperative CBD imaging with ERCP or POC and three of these developed early symptomatic retained stones. This group requires further follow-up.

Laparoscopic hernia repair in Leicester General Hospital: a prospective audit of 94 patients.

Conventional hernia repair is effective in terms of cure but is associated with considerable postoperative pain and delay in return to normal activity. Laparoscopic repair has the potential to reduce pain and speed return to normal activity, but there have been few published reports of the outcome of this operation in the UK. We present a prospective audit of 94 patients who underwent laparoscopic repair. Of the 94 patients, 87 (92.6%) were male and 7 (7.4%) were female. Thirteen of the repairs were bilateral and 12 were recurrent. Two had to be converted to open repair. The mean operating time for unilateral repair was 56 min and for bilateral repair 98 min. Sixty-three patients (67%) were discharged within 24 h and 21 (22.4%) were discharged within 48 h. There were minor complications in 20 patients (21%), eight of whom (8.5%) developed a haematoma. The other minor complications included seromas (2), bruising at the site of the entry port (2), hyperaesthesia in the groin (2), port hernia (1), shoulder tip pain after surgery (3) and postoperative urinary retention (2). Nine (9.5%) patients claimed to have had no pain or discomfort at all; 35 (37.2%) were pain and discomfort free in 2 weeks. Thirty-two (34%) patients returned to normal activities in 2 weeks. With a median follow-up of 8 months 3 (3.2%) recurrences were noted. It is emphasised that this series represents a learning curve and that the operation is developmental. We are now restricting laparoscopic repair to recurrent and bilateral hernias where the technique offers particular advantages.

Factors influencing peritoneal catheter survival in continuous ambulatory peritoneal dialysis.

The success of continuous ambulatory peritoneal dialysis (CAPD) is to a great extent determined by the survival of the peritoneal catheter. The aim of this study was to identify technical factors which influence CAPD catheter survival. A total of 453 CAPD catheters inserted into 310 patients over an 8-year period were analysed. Access to the peritoneum was gained either by an open surgical technique (n = 290) or by a closed technique using a trocar and introducer (n = 163). Data relating to a number of potentially significant risk/benefit factors were analysed using multiple regression analysis (proportional hazards method of Cox). Three factors were found to be independently associated with improved catheter survival. They were: using an open surgical insertion technique, performing a partial omentectomy at the time of catheter insertion and the procedure being performed by a consultant.

Urological complications of renal transplantation: the impact of double J ureteric stents.

In a 10 year series of 350 consecutive renal transplant operations, the overall urological complication rate was 7.7%. During this period double J stents were introduced and were used either in the treatment of actual urological complications or as a prophylactic measure to protect ureters which had been damaged at retrieval. A total of 34 double J stents were used in 33 patients. The indications were: ureteric obstruction (n = 13), urinary leak (n = 5), short transplant ureter anastomosed using an extravesical ureteroneocystostomy (n = 10) and ureteric injury at the time of organ retrieval (n = 6). Thirty-two double J stents were inserted at open operation and two were inserted by an antegrade method after percutaneous nephrostomy. Improvement in renal function occurred in 16 out of the 18 cases of urological complications. No kidneys were lost and there were no deaths as a direct result of these complications. In a number of cases the insertion of a double J stent was the only treatment, thus eliminating the need for more complex surgery. All 16 patients who had a ureteric stent inserted as a prophylactic measure at the time of transplantation made uncomplicated postoperative recoveries. Urinary tract infection was relatively common (27%) after double J stent insertion, but other complications were rare. In conclusion, double J stents have proved to be a useful adjunct in the management of renal transplant related urological complications.

Intraoperative parathyroid hormone estimation: a valuable adjunct to parathyroid surgery.

Serial measurements of serum intact parathyroid hormone (PTH) and adjusted total calcium levels were performed on 10 patients during unilateral neck exploration for a solitary parathyroid adenoma localised preoperatively by ultrasound scan. Frozen section was performed peroperatively to establish the presence of parathyroid tissue. Levels of PTH were shown to be within the normal range within 15 min of adenoma removal (a mean of 13.4% of their preoperative values), allowing clear early distinction from unsuccessful surgery where no change occurred. Frozen section wrongly identified thyroid tissue as parathyroid in one case leading to a failure of the initial neck exploration. Our findings show that intraoperative PTH measurements can accurately predict whether all hyperfunctioning parathyroid tissue has been removed. This is not always possible using frozen section techniques. The wider use of intraoperative PTH measurement, particularly in difficult cases, may avoid the need for prolonged explorations to identify all four glands and, perhaps, biopsy of normal glands, replacing the current standard use of frozen section as a more reliable indicator of the success of parathyroid surgery.