Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P = .009), decreased expression of injury biomarker NGAL (P = .012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P = .019, medulla P = .001), downregulation of interleukin (IL)-1ß (P = .050), and upregulation of IL-10 (P < .047) and Indolamine-2, 3-dioxygenase (P = .050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P < .001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

Prehabilitation prior to surgery for pancreatic cancer: A systematic review.

INTRODUCTION: Prehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection. METHODS: A systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting. RESULTS: Six studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes. CONCLUSION: Early evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

BACKGROUND: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. METHODS: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. RESULTS: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52-0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs 27% OR 0.39 (CI 0.22-0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44-0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34-0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05-0.32), p = 0.015). CONCLUSION: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.

Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials.

BACKGROUND: Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. METHODS: A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. RESULTS: Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. CONCLUSIONS: Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.

A Systematic Review and Network-Meta-Analysis of Gastro-Enteric Reconstruction Techniques Following Pancreatoduodenectomy to Reduce Delayed Gastric Emptying.

INTRODUCTION: This network meta-analysis aimed to identify the reconstruction technique associated with lowest rates of DGE following pancreatoduodenectomy (PD) from randomised controlled trials (RCTs). METHODS: A systematic literature search of PubMed, Embase and MEDLINE databases was carried out using the PRISMA framework to identify all RCTs comparing reconstruction techniques of gastrojejunostomy after PD, with overall DGE as the primary endpoint. The primary outcome measure was overall DGE. Secondary outcomes were grade B/C DGE, duration of nasogastric tube, time to solid food intake, overall and grade B/C pancreatic fistula, bile leaks, reoperation, length of hospital stay and in-hospital mortality. RESULTS: The search strategy identified eight RCTs including 761 patients. Six RCTs compared antecolic (n = 291 patients) and retrocolic Billroth II (n = 289 patients) reconstruction (n = 6 studies), and two RCTs compared antecolic Billroth II (n = 92 patients) and Roux-en-Y (n = 89 patients) reconstruction. Overall, antecolic Billroth II ranked best for overall and grade B/C DGE, bile leak, surgical site infection, length of stay and in-hospital mortality. Roux-en-Y was best for overall and grade B/C pancreatic fistula. CONCLUSION: Antecolic Billroth II gastroenteric reconstruction is associated with the lowest rates of delayed gastric emptying after PD amongst the currently available techniques of gastrojejunostomy reconstructions.

A systematic review and network meta-analysis of parenchymal transection techniques during hepatectomy: an appraisal of current randomised controlled trials.

BACKGROUND: Major liver resection can lead to significant morbidity and mortality. Blood loss is one of the most important factors predicting a good outcome. Although various transection methods have been reported, there is no consensus on the best technique. This systematic review and network meta-analysis aims to characterise and identify the best reported technique for elective parenchymal liver transection based on published randomised controlled trials (RCT's). METHODS: A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Central to identify RCT's up to 5th June 2019 that examined parenchymal transection for liver resection. Data including study characteristics and outcomes including intraoperative (blood loss, operating time) and postoperative measures (overall and major complications, bile leaks) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. RESULTS: This study identified 22 RCT's involving 2360 patients reporting ten parenchymal transection techniques. Bipolar cautery has lower blood loss and shorter operating time than stapler (mean difference: 85 mL; 22min) and Tissue Link (mean difference: 66 mL; 29min). Bipolar cautery was ranked first for blood loss and operating time followed by stapler and TissueLink. Harmonic scalpel is associated with lower overall complications than Hydrojet (Odds ratio (OR): 0.48), BiClamp forceps (OR: 0.46) and clamp crushing (OR: 0.41). CONCLUSION: Bipolar cautery techniques appear to best at reducing blood loss and associated with shortest operating time. In contrast, Harmonic scalpel appears best for overall and major complications. Given the paucity of data and selective outcome reporting, it is still hard to identify what is the best technique for liver resection. Therefore, further high-quality large-scale RCT's are still needed.

Review of abdominal solid organ transplantation in Jehovah's Witness patients.

Managing blood loss in Jehovah's Witness (JW) patients is a matter of controversy. These patients will not accept transfusions of red blood cells, white blood cells, platelets or plasma, even if that is required to save their lives. There are many discussions regarding safety of operating upon JW patients in general surgical procedures, but in solid organ transplantation there is a paucity of literature on this subject. We have reviewed individual case reports and small series documenting on experience with solid organ transplantation in JW patients and the strategies adopted to facilitate that. It is clear that such patients require the surgical team to dedicate more time to ensure their safe management. This begins with a thorough, detailed consent of exactly which products and interventions they will or will not accept. Planning must begin weeks before surgery if possible. Each case must be assessed individually, but provided they meet fitness requirements, there are no absolute contraindications to abdominal organ transplantation.

Endoscopic ultrasound-guided fine-needle biopsy is superior to fine-needle aspiration in assessing pancreatic neuroendocrine tumors.

Background and study aims Pancreatic neuroendocrine tumors (PanNETs) outcomes are dependent upon grading by Ki67. This study compared endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) to fine-needle aspiration (FNA) in assessing PanNETs. Patients and methods All pancreatic histology for PanNET between January 2009 and June 2017 was included if EUS sampling was performed prior to surgical resection. Ki67 and grade from FNA and FNB samples was compared to surgical histology using correlation coefficient and kappa values. Subgroup analysis was performed for purely solid lesions, lesions < 2 cm and FNB needle type. Results One hundred sixity-four patients had PanNET of which 57 underwent surgical resection. Thirty-five lesions underwent FNA and 26 FNB (4 had both) confirming PanNET. 23/ of 35 FNA samples reported Ki67/grading compared to all 26 FNB samples ( P  = 0.0006). Compared to surgical histology, Ki67 on FNA correlated poorly overall (r = -0.08), in solid lesions (r = -0.102) and lesions < 2 cm (r = -0.149) whereas FNB correlated moderately overall (r = 0.65), in solid lesions (r = 0.64) and lesions < 2 cm (r = 0.61). Tumor grade showed poor agreement (kappa) with FNA overall (0.026), in solid lesions (0.044) and lesions < 2 cm (0.00) whereas FNB showed moderate-good agreement overall (0.474), in solid lesions (0.58) and lesions < 2 cm (0.745). Fork-tip FNB needles Ki67 showed strong correlation with surgical histology (r = 0.788) compared to reverse bevel FNB needles (r = 0.521). Both FNB needles showed moderate agreement with tumor grade. Conclusion FNB samples were significantly more likely than FNA to provide adequate material for Ki67/grading and showed a closer match to surgical histology. FNB needle types require prospective investigation.

UK registry analysis of donor substance misuse and outcomes following pancreas transplantation.

Substance abuse is unfortunately common in organ donors. Often, these organs are declined for transplant, not only because of concerns around blood-borne virus transmission but also because of perceived poor outcomes. In kidney transplantation, previous studies have demonstrated donor smoking status significantly impacts transplant outcome, but intravenous drug use or alcohol dependence does not. This study aims to clarify these issues in pancreas transplantation. Retrospective data on all UK solid organ pancreas transplants from 1994 to 2015 were obtained from the NHSBT UK Transplant Registry. The impact of illicit drug misuse, alcohol abuse, and smoking on graft and patient survival were analyzed using Kaplan-Meier plots and a Cox regression model. A total of 1175 of the 2317 (49.5%) donors were categorized as substance misusers. Univariate survival analysis revealed no significant impact of substance misuse on 10-year graft or patient survival. Multivariate analysis confirmed substance misuse was not associated with impaired graft or patient survival. A history of donor substance misuse does not negatively impact 10-year graft or patient survival following pancreas transplantation. This is a large national registry analysis with long-term follow-up data and should therefore provide clinicians with reassurance when considering pancreas grafts from substance misuse donors.

Antibody induction versus corticosteroid induction for liver transplant recipients.

BACKGROUND: Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell specific antibody induction compared with corticosteroid induction of immunosuppression after liver transplantation. OBJECTIVES: To assess the benefits and harms of T-cell specific antibody induction versus corticosteroid induction for prevention of acute rejection in liver transplant recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 September 2013 together with reference checking, citation searching, contact with trial authors and pharmaceutical companies to identify additional trials. SELECTION CRITERIA: We included all randomised clinical trials assessing immunosuppression with T-cell specific antibody induction versus corticosteroid induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should have received the same maintenance immunosuppressive therapy. DATA COLLECTION AND ANALYSIS: We used RevMan for statistical analysis of dichotomous data with risk ratio (RR) and of continuous data with mean difference (MD), both with 95% confidence intervals (CIs). We assessed risk of systematic errors (bias) using bias risk domains with definitions. We used trial sequential analysis to control for random errors (play of chance). MAIN RESULTS: We included 10 randomised trials with a total of 1589 liver transplant recipients, which studied the use of T-cell specific antibody induction versus corticosteroid induction. All trials were with high risk of bias. We compared any kind of T-cell specific antibody induction versus corticosteroid induction in 10 trials with 1589 participants, including interleukin-2 receptor antagonist induction versus corticosteroid induction in nine trials with 1470 participants, and polyclonal T-cell specific antibody induction versus corticosteroid induction in one trial with 119 participants.Our analyses showed no significant differences regarding mortality (RR 1.01, 95% CI 0.72 to 1.43), graft loss (RR 1.12, 95% CI 0.82 to 1.53) and acute rejection (RR 0.84, 95% CI 0.70 to 1.00), infection (RR 0.96, 95% CI 0.85 to 1.09), hepatitis C virus recurrence (RR 0.89, 95% CI 0.79 to 1.00), malignancy (RR 0.59, 95% CI 0.13 to 2.73), and post-transplantation lymphoproliferative disorder (RR 1.00, 95% CI 0.07 to 15.38) when any kind of T-cell specific antibody induction was compared with corticosteroid induction (all low-quality evidence). Cytomegalovirus infection was less frequent in patients receiving any kind of T-cell specific antibody induction compared with corticosteroid induction (RR 0.50, 95% CI 0.33 to 0.75; low-quality evidence). This was also observed when interleukin-2 receptor antagonist induction was compared with corticosteroid induction (RR 0.55, 95% CI 0.37 to 0.83; low-quality evidence), and when polyclonal T-cell specific antibody induction was compared with corticosteroid induction (RR 0.21, 95% CI 0.06 to 0.70; low-quality evidence). However, when trial sequential analysis regarding cytomegalovirus infection was applied, the required information size was not reached. Furthermore, diabetes mellitus occurred less frequently when T-cell specific antibody induction was compared with corticosteroid induction (RR 0.45, 95% CI 0.34 to 0.60; low-quality evidence), when interleukin-2 receptor antagonist induction was compared with corticosteroid induction (RR 0.45, 95% CI 0.35 to 0.61; low-quality evidence), and when polyclonal T-cell specific antibody induction was compared with corticosteroid induction (RR 0.12, 95% CI 0.02 to 0.95; low-quality evidence). When trial sequential analysis was applied, the trial sequential monitoring boundary for benefit was crossed. We found no subgroup differences for type of interleukin-2 receptor antagonist (basiliximab versus daclizumab). Four trials reported on adverse events. However, no differences between trial groups were noted. Limited data were available for meta-analysis on drug-specific adverse events such as haematological adverse events for antithymocyte globulin. No data were available on quality of life. AUTHORS' CONCLUSIONS: Because of the low quality of the evidence, the effects of T-cell antibody induction remain uncertain. T-cell specific antibody induction seems to reduce diabetes mellitus and may reduce cytomegalovirus infection when compared with corticosteroid induction. No other clear benefits or harms were associated with the use of T-cell specific antibody induction compared with corticosteroid induction. For some analyses, the number of trials investigating the use of T-cell specific antibody induction after liver transplantation is small, and the numbers of participants and outcomes in these randomised trials are limited. Furthermore, the included trials are heterogeneous in nature and have applied different types of T-cell specific antibody induction therapy. All trials were at high risk of bias. Hence, additional randomised clinical trials are needed to assess the benefits and harms of T-cell specific antibody induction compared with corticosteroid induction for liver transplant recipients. Such trials ought to be conducted with low risks of systematic error and of random error.

Antibody induction versus placebo, no induction, or another type of antibody induction for liver transplant recipients.

BACKGROUND: Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell antibody induction for preventing rejection after liver transplantation. OBJECTIVES: To assess the benefits and harms of immunosuppressive T-cell specific antibody induction compared with placebo, no induction, or another type of T-cell specific antibody induction for prevention of acute rejection in liver transplant recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) until September 2013. SELECTION CRITERIA: Randomised clinical trials assessing immunosuppression with T-cell specific antibody induction compared with placebo, no induction, or another type of antibody induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should have received the same maintenance immunosuppressive therapy. We planned to include trials with all of the different types of T-cell specific antibodies that are or have been used for induction (ie., polyclonal antibodies (rabbit of horse antithymocyte globulin (ATG), or antilymphocyte globulin (ALG)), monoclonal antibodies (muromonab-CD3, anti-CD2, or alemtuzumab), and interleukin-2 receptor antagonists (daclizumab, basiliximab, BT563, or Lo-Tact-1)). DATA COLLECTION AND ANALYSIS: We used RevMan analysis for statistical analysis of dichotomous data with risk ratio (RR) and of continuous data with mean difference (MD), both with 95% confidence intervals (CIs). We assessed the risk of systematic errors (bias) using bias risk domains with definitions. We used trial sequential analysis to control for random errors (play of chance). We presented outcome results in a summary of findings table. MAIN RESULTS: We included 19 randomised clinical trials with a total of 2067 liver transplant recipients. All 19 trials were with high risk of bias. Of the 19 trials, 16 trials were two-arm trials, and three trials were three-arm trials. Hence, we found 25 trial comparisons with antibody induction agents: interleukin-2 receptor antagonist (IL-2 RA) versus no induction (10 trials with 1454 participants); monoclonal antibody versus no induction (five trials with 398 participants); polyclonal antibody versus no induction (three trials with 145 participants); IL-2 RA versus monoclonal antibody (one trial with 87 participants); and IL-2 RA versus polyclonal antibody (two trials with 112 participants). Thus, we were able to compare T-cell specific antibody induction versus no induction (17 trials with a total of 1955 participants). Overall, no difference in mortality (RR 0.91; 95% CI 0.64 to 1.28; low-quality of evidence), graft loss including death (RR 0.92; 95% CI 0.71 to 1.19; low-quality of evidence), and adverse events ((RR 0.97; 95% CI 0.93 to 1.02; low-quality evidence) outcomes was observed between any kind of T-cell specific antibody induction compared with no induction when the T-cell specific antibody induction agents were analysed together or separately. Acute rejection seemed to be reduced when any kind of T-cell specific antibody induction was compared with no induction (RR 0.85, 95% CI 0.75 to 0.96; moderate-quality evidence), and when trial sequential analysis was applied, the trial sequential monitoring boundary for benefit was crossed before the required information size was obtained. Furthermore, serum creatinine was statistically significantly higher when T-cell specific antibody induction was compared with no induction (MD 3.77 µmol/L, 95% CI 0.33 to 7.21; low-quality evidence), as well as when polyclonal T-cell specific antibody induction was compared with no induction, but this small difference was not clinically significant. We found no statistically significant differences for any of the remaining predefined outcomes - infection, cytomegalovirus infection, hepatitis C recurrence, malignancy, post-transplant lymphoproliferative disease, renal failure requiring dialysis, hyperlipidaemia, diabetes mellitus, and hypertension - when the T-cell specific antibody induction agents were analysed together or separately. Limited data were available for meta-analysis on drug-specific adverse events such as haematological adverse events for antithymocyte globulin. No data were found on quality of life.When T-cell specific antibody induction agents were compared with another type of antibody induction, no statistically significant differences were found for mortality, graft loss, and acute rejection for the separate analyses. When interleukin-2 receptor antagonists were compared with polyclonal T-cell specific antibody induction, drug-related adverse events were less common among participants treated with interleukin-2 receptor antagonists (RR 0.23, 95% CI 0.09 to 0.63; low-quality evidence), but this was caused by the results from one trial, and trial sequential analysis could not exclude random errors. We found no statistically significant differences for any of the remaining predefined outcomes: infection, cytomegalovirus infection, hepatitis C recurrence, malignancy, post-transplant lymphoproliferative disease, renal failure requiring dialysis, hyperlipidaemia, diabetes mellitus, and hypertension. No data were found on quality of life. AUTHORS' CONCLUSIONS: The effects of T-cell antibody induction remain uncertain because of the high risk of bias of the randomised clinical trials, the small number of randomised clinical trials reported, and the limited numbers of participants and outcomes in the trials. T-cell specific antibody induction seems to reduce acute rejection when compared with no induction. No other clear benefits or harms were associated with the use of any kind of T-cell specific antibody induction compared with no induction, or when compared with another type of T-cell specific antibody. Hence, more randomised clinical trials are needed to assess the benefits and harms of T-cell specific antibody induction compared with placebo, and compared with another type of antibody, for prevention of rejection in liver transplant recipients. Such trials ought to be conducted with low risks of systematic error (bias) and low risk of random error (play of chance).

Chemotherapy-associated liver injury in patients with colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: Chemotherapy-associated liver injury is a major cause for concern when treating patients with colorectal liver metastases. The aim of this review was to determine the pathological effect of specific chemotherapy regimens on the hepatic parenchyma as well as on surgical morbidity, mortality and overall survival. METHODS: A systematic review of the published literature and a meta-analysis were performed. For each of the variables under consideration, the effects of different chemotherapy regimens were determined by calculation of relative risks by a random-effects model. RESULTS: Hepatic parenchymal injury is regimen specific, with oxaliplatin-based regimens being associated with grade 2 or greater sinusoidal injury (number needed to harm 8; 95 % confidence interval [CI] 6.4-13.6), whereas irinotecan-based regimens associated with steatohepatitis (number needed to harm 12; 95 % CI 7.8-26). The use of bevacizumab alongside FOLFOX reduces the risk of grade 2 or greater sinusoidal injury (relative risk 0.34; 95 % CI 0.15-0.75). CONCLUSIONS: Chemotherapy before resection of colorectal liver metastases is associated with an increased risk of regimen-specific liver injury. This liver injury may have implications for the functional reserve of the liver for patients undergoing major hepatectomy for colorectal liver metastases.

Endoscopic botulinum toxin injection for the treatment of diabetic gastropathy in pancreas and islet-cell transplant patients.

OBJECTIVES: Gastroparesis is a well-recognized, long-term complication of diabetes. Prokinetic drugs are often not effective, prompting the development of alternative therapies. We report our experience of using one such alternative, endoscopic botulinum toxin injection, to ameliorate diabetic gastropathy in association with pancreas and islet-cell transplant patients. MATERIALS AND METHODS: Three male diabetic patients aged 42 to 55 years had been treated with botulinum toxin in our center. Two patients were both after-simultaneous pancreas-kidney transplant and 1 was awaiting islet-cell transplant after pancreatectomy. Mechanical gastric outlet obstruction was first excluded by radiological and endoscopic studies. Between 100 and 200 IU of toxin were then injected in the prepyloric region using an endoscopic technique. A subjective scoring scale was used to assess symptoms before and after botulinum therapy. RESULTS: Improvement in subjective symptom severity scoring was seen in all patients, with a posttreatment improvement from 55% to 91%. Such improvement was temporary in 2 patients and long-lasting in 1 patient. CONCLUSIONS: The time for improvement of gastric autonomic function after pancreas or islet-cell transplantation remains unclear. Some patients may continue to be symptomatic, leading to increasing morbidity. However, endoscopic botulinum injections may provide short-term relief while waiting for improvement and spare patients the morbidity associated with more-invasive therapies.

Laparoscopic versus open nephrectomy for live kidney donors.

BACKGROUND: Waiting lists for kidney transplantation continue to grow and live organ donation has become more important as the number of brain stem dead cadaveric organ donors continues to fall. The major disincentive to potential kidney donors is the pain and morbidity associated with open surgery. OBJECTIVES: To identify the benefits and harms of using laparoscopic compared to open nephrectomy techniques to recover kidneys from live organ donors. SEARCH METHODS: We searched the online databases CENTRAL (in The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to January 2010) and EMBASE (January 1980 to January 2010) and handsearched textbooks and reference lists. SELECTION CRITERIA: Randomised controlled trials comparing laparoscopic donor nephrectomy (LDN) with open donor nephrectomy (ODN). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. MAIN RESULTS: Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta-analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0.06 to 1.48), delayed graft function (RR 1.09, 95% CI 0.52 to 2.30), acute rejection (RR 1.41, 95 % CI 0.87 to 2.27), ureteric complications (RR 1.51, 95% CI 0.69 to 3.31), kidney function at one year (SMD 0.15, 95% CI -0.11 to 0.41) or graft loss at one year (RR 0.76, 95% CI 0.15 to 3.85). AUTHORS' CONCLUSIONS: LDN is associated with less pain compared with open surgery; however, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using LDN procedures were exposed to longer warm ischaemia periods than ODN-acquired grafts, although this has not been reported as being associated with short-term consequences.

Laparoscopic liver resection for hepatic adenoma in pregnancy.

INTRODUCTION: Liver cell adenomas (LCA) can present during pregnancy with abdominal pain and bleeding. Assessment and management at this time are complicated by concerns over fetal well-being. METHODS: We reviewed cases from our own institution, including the only laparoscopic liver resection reported in pregnancy, and systematically reviewed the literature to identify successful management strategies for this clinical dilemma. RESULTS: Two cases of surgery for bleeding liver adenoma were identified in our own institution. One case was managed with an elective laparoscopic segmental resection at 16 weeks and 1 with open surgery and successful fetal delivery at 32 weeks gestation. In the second case hepatic rupture of a 3.5-cm lesion was precipitated by diagnostic biopsy. In the world literature, spontaneous rupture of an LCA during pregnancy has been reported in 19 cases and is associated with maternal mortality and fetal loss approaching 50%. CONCLUSIONS: We advocate an aggressive approach to management of LCA in pregnancy owing to the high mortality associated with rupture. Biopsy of LCA in pregnancy is unsafe and can be complicated by rupture. Hence, patients presenting de novo with clinical or radiologic signs of bleeding or large (>5 cm) undiagnosed lesions should be offered laparoscopic resection if feasible.