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Background: The 5-year graft survival rate of donor kidneys transplanted in the Eurotransplant Senior Program (ESP) is only 47 per cent. Normothermic machine perfusion (NMP) may be a new preservation technique that improves graft outcome. This pilot study aimed to assess safety and feasibility of this technique within the ESP., Methods: Recipients were eligible for inclusion if they received a donor kidney within the ESP. Donor kidneys underwent 2 h of oxygenated NMP with a red cell-based solution at 37°C, additional to standard-of-care preservation (non-oxygenated hypothermic machine perfusion). The primary outcome was the safety and feasibility of NMP. As a secondary outcome, graft outcome was investigated and compared with that in a historical group of patients in the ESP and the contralateral kidneys., Results: Eleven patients were included in the NMP group; the function of eight kidneys could be compared with that of the contralateral kidney. Fifty-three patients in the ESP, transplanted consecutively between 2016 and 2018, were included as controls. No adverse events were noted, especially no arterial thrombosis or primary non-function of the transplants. After 120 min of oxygenated NMP, median flow increased from 117 (i.q.r. 80-126) to 215 (170-276) ml/min (P = 0.001). The incidence of immediate function was 64 per cent in the NMP group and 40 per cent in historical controls (P = 0.144). A significant difference in graft outcome was not observed., Discussion: This pilot study showed NMP to be safe and feasible in kidneys transplanted in the ESP. A well powered study is warranted to confirm these results and investigate the potential advantages of NMP on graft outcome., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit., Methods: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien-Dindo grade IIIA or higher) and 30-day or in-hospital mortality., Results: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20-69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events., Conclusion: Hospital volume and postoperative outcomes were not associated., (© 2020 The Authors. British Journal of Surgery published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Background: Hepatocellular adenoma (HCA) larger than 5 cm in diameter has an increased risk of haemorrhage and malignant transformation, and is considered an indication for resection. As an alternative to resection, transarterial embolization (TAE) may play a role in prevention of complications of HCA, but its safety and efficacy are largely unknown. The aim of this study was to assess outcomes and postembolization effects of selective TAE in the management of HCA., Methods: This retrospective, multicentre cohort study included patients aged at least 18 years, diagnosed with HCA and treated with TAE. Patient characteristics, 30-day complications, tumour size before and after TAE, symptoms before and after TAE, and need for secondary interventions were analysed., Results: Overall, 59 patients with a median age of 33.5 years were included from six centres; 57 of the 59 patients were women. Median tumour size at time of TAE was 76 mm. Six of 59 patients (10 per cent) had a major complication (cyst formation or sepsis), which could be resolved with minimal therapy, but prolonged hospital stay. Thirty-four patients (58 per cent) were symptomatic at presentation. There were no significant differences in symptoms before TAE and symptoms evaluated in the short term (within 3 months) after TAE (P = 0·134). First follow-up imaging was performed a median of 5·5 months after TAE and showed a reduction in size to a median of 48 mm (P < 0·001)., Conclusion: TAE is safe, can lead to adequate size reduction of HCA and, offers an alternative to resection in selected patients., (© 2019 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Background: Hepatocellular adenoma (HCA) is a benign liver tumour that may be complicated by bleeding or malignant transformation. Present guidelines advise cessation of oral contraceptives and surgical resection if the lesion is still larger than 5 cm at 6 months after diagnosis. The aim of this study was to evaluate whether this 6-month interval is sufficient to expect regression of a large HCA to 5 cm or smaller., Methods: This retrospective cohort study included all patients with an HCA larger than 5 cm diagnosed between 1999 and 2015 with follow-up of at least 6 months. Medical records were reviewed for patient characteristics, clinical presentation, lesion characteristics, management and complications. Differences in characteristics were assessed between patients kept under surveillance and those who underwent treatment for an HCA larger than 5 cm., Results: Some 194 patients were included, of whom 192 were women. Eighty-six patients were kept under surveillance and 108 underwent HCA treatment. Patients in the surveillance group had a significantly higher BMI (P = 0·029), smaller baseline HCA diameter (P < 0·001), more centrally located lesions (P < 0·001) and were more likely to have multiple lesions (P = 0·001) than those in the treatment group. There were no significant differences in sex, age at diagnosis, symptoms, complication rates and HCA subtype distribution. Time-to-event analysis in patients managed conservatively and those still undergoing treatment more than 6 months after diagnosis showed that 69 of 118 HCAs (58·5 per cent) regressed to 5 cm or smaller after a median of 104 (95 per cent c.i. 80-128) weeks. Larger HCAs took longer to regress (P < 0·001). No complications were documented during follow-up., Conclusion: This study suggests that a 6-month cut-off point for assessment of regression of HCA larger than 5 cm to no more than 5 cm is too early. As no complications were documented during follow-up, the cut-off point in women with typical, non-β-catenin-activated HCA could be prolonged to 12 months, irrespective of baseline diameter., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Transplant surgery is facing a shortage of deceased donor organs. In response, the criteria for organ donation have been extended, and an increasing number of organs from older donors are being used. For recipients, the benefits of transplantation are great, and the growing ageing population has led to increasing numbers of elderly patients being accepted for transplantation., Methods: The literature was reviewed to investigate the impact of age of donors and recipients in abdominal organ transplantation, and to highlight aspects of the fine balance in donor and recipient selection and screening, as well as allocation policies fair to young and old alike., Results: Overall, kidney and liver transplantation from older deceased donors have good outcomes, but are not as good as those from younger donors. Careful donor selection based on risk indices, and potentially biomarkers, special allocation schemes to match elderly donors with elderly recipients, and vigorous recipient selection, allows good outcomes with increasing age of both donors and recipients. The results of live kidney donation have been excellent for donor and recipient, and there is a trend towards inclusion of older donors. Future strategies, including personalized immunosuppression for older recipients as well as machine preservation and reconditioning of donor organs, are promising ways to improve the outcome of transplantation between older donors and older recipients., Conclusion: Kidney and liver transplantation in the elderly is a clinical reality. Outcomes are good, but can be optimized by using strategies that modify donor risk factors and recipient co-morbidities, and personalized approaches to organ allocation and immunosuppression., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Preoperative risk assessment in cancer surgery is of importance to improve treatment and outcome. The aim of this study was to assess the impact of CT-assessed sarcopenia on short- and long-term outcomes in patients undergoing surgical resection of gastrointestinal and hepatopancreatobiliary malignancies., Methods: A systematic search of Embase, PubMed and Web of Science was performed to identify relevant studies published before 30 September 2014. PRISMA guidelines for systematic reviews were followed. Screening for inclusion, checking the validity of included studies and data extraction were carried out independently by two investigators., Results: After screening 692 records, 13 observational studies with a total of 2884 patients were included in the analysis. There was wide variation in the reported prevalence of sarcopenia (17.0-79 per cent). Sarcopenia was independently associated with reduced overall survival in seven of ten studies, irrespective of tumour site. Hazard ratios (HRs) of up to 3.19 (hepatic cancer), 1.63 (pancreatic cancer), 1.85 (colorectal cancer) and 2.69 (colorectal liver metastases, CLM) were reported. For oesophageal cancer, the HR was 0.31 for increasing muscle mass. In patients with colorectal cancer and CLM, sarcopenia was independently associated with postoperative mortality (colorectal cancer: odds ratio (OR) 43.3), complications (colorectal cancer: OR 0.96 for increasing muscle mass; CLM: OR 2.22) and severe complications (CLM: OR 3.12)., Conclusion: Sarcopenia identified before surgery by single-slice CT is associated with impaired overall survival in gastrointestinal and hepatopancreatobiliary malignancies, and increased postoperative morbidity in patients with colorectal cancer with or without hepatic metastases., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Although benign in itself, hepatocellular adenoma (HCA) can be complicated by hormone-induced growth, and subsequent haemorrhage and rupture. The exact risk of haemorrhage and rupture is not known. This systematic review of the literature was carried out with the aim of estimating the risk of haemorrhage and rupture in HCA., Methods: A systematic literature search of the PubMed and Embase databases was performed for all articles relevant to haemorrhage and/or rupture of HCA, published between 1969 and March 2011., Results: Twenty-eight articles met the selection criteria, containing a total of 1176 patients. Haemorrhage was reported with an overall frequency of 27·2 per cent among patients, and in 15·8 per cent of all HCA lesions. Rupture and intraperitoneal bleeding were reported in 17·5 per cent of patients. Bleeding was the first symptom in 68·5 per cent of patients with a bleeding HCA. Six of 13 articles reporting the size of HCA lesions in which bleeding occurred mentioned haemorrhage in HCAs smaller than 5 cm., Conclusion: Haemorrhage and rupture are common in patients with HCA., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Recent evidence suggests that depletion of skeletal muscle mass (sarcopenia) and an increased amount of intra-abdominal fat (central obesity) influence cancer statistics. This study investigated the impact of sarcopenia and central obesity on survival in patients undergoing liver resection for colorectal liver metastases (CLM)., Methods: Diagnostic imaging from patients who had hepatic resection for CLM in one centre between 2001 and 2009, and who had assessable perioperative computed tomograms, was analysed retrospectively. Total cross-sectional areas of skeletal muscle and intra-abdominal fat, and their influence on outcome, were analysed., Results: Of the 196 patients included in the study, 38 (19·4 per cent) were classified as having sarcopenia. Five-year disease-free (15 per cent versus 28·5 per cent in patients without sarcopenia; P = 0·002) and overall (20 per cent versus 49·9 per cent respectively; P < 0·001) survival rates were lower for patients with sarcopenia at a median follow-up of 29 (range 1-97) months. Sarcopenia was an independent predictor of worse recurrence-free (hazard ratio (HR) 1·88, 95 per cent confidence interval 1·25 to 2·82; P = 0·002) and overall (HR 2·53, 1·60 to 4·01; P < 0·001) survival. Central obesity was associated with an increased risk of recurrence in men (P = 0·032), but not in women (P = 0·712)., Conclusion: Sarcopenia has a negative impact on cancer outcomes following resection of CLM., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

There is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose tissue-derived mesenchymal stem cells (ASC) were cultured with alloactivated peripheral blood mononuclear cells (PBMC) (mixed lymphocyte reaction: MLR), with proinflammatory cytokines [interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-6] or under control conditions, and their full genome expression and function examined. Proinflammatory cytokines mainly increased indoleamine-2,3-dioxygenase expression, whereas ASC cultured with MLR showed increased expression of COX-2, involved in prostaglandin E(2) production. Both conditions had a stimulatory, but differential, effect on the expression of proinflammatory cytokines and chemokines, while the expression of fibrotic factors was decreased only in response to proinflammatory cytokines. Functional analysis demonstrated that inflammatory conditions affected morphology and proliferation of ASC, while their differentiation capacity and production of trophic factors was unaffected. The immunosuppressive capacity of ASC was enhanced strongly under inflammatory conditions. In conclusion, ASC showed enhanced immunosuppressive capacity under inflammatory conditions, while their differentiation capacity was preserved. Therefore, in vitro preconditioning provides ASC with improved properties for immediate clinical immune therapy., (© 2010 Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.)

Background: The risk of major hepatic resection in patients with hepatic steatosis remains controversial. A meta-analysis was performed to establish the best estimate of the impact of steatosis on patient outcome following major hepatic surgery., Methods: A systematic search was performed following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Risk ratios (RRs) for complication and mortality rates were calculated for patients with no, less than 30 per cent and at least 30 per cent steatosis, and a meta-analysis was carried out., Results: Of six observational studies identified, four including a total of 1000 patients were subjected to meta-analysis; two others were tabulated separately. Compared with patients without steatosis, those with less than 30 per cent and at least 30 per cent steatosis had a significantly increased risk of postoperative complications, with a RR of 1.53 (95 per cent confidence interval (c.i.) 1.27 to 1.85) and 2.01 (1.66 to 2.44) respectively. Patients with at least 30 per cent steatosis had an increased risk of postoperative death (RR 2.79, 95 per cent c.i. 1.19 to 6.51)., Conclusion: Patients with steatosis had an up to twofold increased risk of postoperative complications, and those with excessive steatosis had an almost threefold increased risk of death., (Copyright 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Stereotactic body radiation therapy (SBRT) is a treatment option for colorectal liver metastases. Local control, patient survival and toxicity were assessed in an experience of SBRT for colorectal liver metastases., Methods: SBRT was delivered with curative intent to 20 consecutively treated patients with colorectal hepatic metastases who were candidates for neither resection nor radiofrequency ablation (RFA). The median number of metastases was 1 (range 1-3) and median size was 2.3 (range 0.7-6.2) cm. Toxicity was scored according to the Common Toxicity Criteria version 3.0. Local control rates were derived on tumour-based analysis., Results: Median follow-up was 26 (range 6-57) months. Local failure was observed in nine of 31 lesions after a median interval of 22 (range 12-52) months. Actuarial 2-year local control and survival rates were 74 and 83 per cent respectively. Hepatic toxicity grade 2 or less was reported in 18 patients. Two patients had an episode of hepatic toxicity grade 3., Conclusion: SBRT is a treatment option for patients with colorectal liver metastases who are not candidates for resection or RFA., ((c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Treatment of suspected hepatocellular adenoma (HA) remains controversial. The aim of this study was to evaluate the management of HA at a time when magnetic resonance imaging (MRI) and computed tomography (CT) are highly sensitive methods for diagnosing HA., Methods: Between January 2000 and January 2005, data from 48 consecutive women with HA (median age 36 years) were prospectively collected. The protocol for diagnostic work-up consisted of multiphasic MRI or CT. Management was observation if the tumour was smaller than 5 cm and surgical intervention if it was 5 cm or larger., Results: The median follow-up was 24 (range 3-73) months. Sixteen (33 per cent) patients had invasive procedures because of tumour size 5 cm or larger, malignant characteristics or haemorrhage. The remaining 32 patients (67 per cent) were observed; haemorrhage and malignant degeneration did not occur and none of the lesions showed enlargement after withdrawal of oral contraceptives. Multiple HAs were found in 32 (67 per cent) patients; liver steatosis was significantly more common in these patients than in those with a solitary lesion (59 versus 19 per cent; P = 0.008)., Conclusion: Observation of adenomas smaller than 5 cm is justified because of improved radiological reliability. Resection should be reserved for patients with malignant tumour characteristics or with single lesions 5 cm or larger.

The effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in peripheral blood of 24 kidney allograft recipients before and after transplantation, and in 23 donors before and after kidney donation. All patients were treated with tacrolimus, mycophenolate mofetil and prednisone. Surgery resulted in a strong decline in the number of myeloid and plasmacytoid DCs, both in kidney donors and in their recipients. However, in donors this effect was transient, as the numbers of both DC subsets had normalized completely by the third postoperative month. In contrast, the recovery of myeloid DC counts in kidney transplant recipients was only incomplete at the end of the 3-month follow-up, despite tapering of immunosuppression. The seven patients who required additional immunosuppressive treatment because of acute rejection experienced an even more marked decrease in DC counts in the early postoperative period compared with patients who remained rejection-free. Surgical procedures markedly affect the numbers of circulating myeloid and plasmacytoid DCs. Immunosuppressive drugs have important additional in vivo effects on this cell type and impair the reconstitution of the myeloid DC subset in peripheral blood after renal transplantation.

Background: The aim was to determine the degree of local control of hepatocellular carcinoma (HCC) in patients with cirrhotic liver disease when treated with ultrasonographically guided interstitial laser coagulation (ILC) with temporary hepatic artery occlusion., Methods: Sixteen patients with 24 HCC tumours were treated. Follow-up was by computed tomography or magnetic resonance imaging every 3 months., Results: Nineteen of 24 tumours showed complete necrosis immediately after treatment, and there was no tumour recurrence during follow-up (mean 14 months, median 12 months). No effect on liver function was observed after 1 week and there was no death. In 13 of the 16 patients, new HCC foci developed at other sites., Conclusion: Percutaneous ILC combined with temporary hepatic artery occlusion during a single session is an effective local treatment for HCC nodules smaller than 5 cm. However, new HCC lesions develop in the majority of patients, which underscores the need for adjuvant therapy or repeated treatment in these patients., (Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

In experimental animals inhibition of T cell co-stimulation immediately after organ transplantation effectively prevents rejection. We investigated whether the expression of co-stimulatory molecules is enhanced in cadaveric liver transplants, whether their expression is influenced by the transplantation procedure, and whether variation in expression between liver transplants is related to the occurrence of acute rejection. Expression of CD80, CD86 and the macrophage marker CD68 were determined by immunohistochemistry in biopsies from 40 clinical liver transplants obtained at different time-points during the transplantation procedure, and in normal liver tissue obtained from 10 human livers. Expression of CD80 and CD86 on Kupffer cells was graded by comparison with CD68-staining. In a subgroup CD80 and CD86 mRNA was quantified by real-time detection polymerase chain reaction. CD86 was expressed in all liver transplants and normal livers on the majority of Kupffer cells. CD80 was absent or sporadically expressed in normal liver tissue, but in 18 of 40 liver transplants at least one-quarter of Kupffer cells expressed CD80. CD80- and CD86-mRNA and protein expression in liver transplants did not change during the warm ischaemic and reperfusion phases of the transplantation procedure. CD80-expression on Kupffer cells varied strongly between individual donor livers; this variation was, however, not significantly related to the occurrence of acute rejection after transplantation. In conclusion, in nearly half of cold-preserved cadaveric liver transplants an increased proportion of Kupffer cells express CD80 at the time of transplantation in comparison with normal liver tissue. The expression was not further induced by warm ischaemia and reperfusion. However, the observed variation in CD80-expression between liver transplants is not a accurate predictive measure for acute rejection.

Background: The unknown natural history and risk of complications of large haemangiomas may pose therapeutic dilemmas. The authors describe their experience with the management of giant haemangiomas., Methods: Patients with a giant haemangioma were identified by a survey of the hospital database. Forty-nine patients with a haemangioma of at least 4 cm in diameter presented between January 1990 and December 2000. Medical records were analysed retrospectively., Results: Eleven patients had surgical treatment and 38 were managed conservatively. The median diameter of the tumours was 8.0 cm in surgically treated patients and 6.0 cm in the group managed by observation. Surgery-related morbidity occurred in three patients, and abdominal complaints persisted in three of ten patients with a symptomatic lesion. During a median follow-up of 52 months, 12 non-operated patients had mild abdominal complaints, considered to be unrelated to the lesion. In these patients symptoms either diminished or became minimal during follow-up. Complications did not occur., Conclusion: Observation of giant haemangiomas can be performed safely. The authors advocate resection of cavernous liver haemangiomas only in patients with persistent severe symptoms.

Stable cadaveric renal transplant patients were routinely converted from cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation to reduce the side effects of long-term immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered to 50% at 2 years after transplantation. We questioned whether a reduction of immunosuppressive treatment results in a rise of donor-specific T-cell reactivity. Before transplantation (no immunosuppression), 1 year (high dose immunosuppression) and 2 years (low dose immunosuppression) after transplantation, the T-cell reactivity of peripheral blood mononuclear cells (PBMC) against donor and third-party spleen cells was tested in mixed lymphocyte cultures (MLC) and against tetanus toxoid (TET) to test the general immune response. We also measured the frequency of donor and third-party reactive helper (HTLpf) and cytotoxic (CTLpf) T-lymphocyte precursors in a limiting dilution assay. Donor-specific responses, calculated by relative responses (RR = donor/third-party reactivity), were determined. Comparing responses after transplantation during high dose immunosuppression with responses before transplantation (no immmunosuppression), the donor-specific MLC-RR (P = 0.04), HTLp-RR (P = 0.04) and CTLp-RR (P = 0.09) decreased, while the TET-reactivity did not change. Comparing the responses during low dose with high dose immunosuppression, no donor- specific differences were found in the MLC-RR, HTLp-RR and CTLp-RR, although TET-reactivity increased considerably (P = 0.0005). We observed a reduction in donor-specific T-cell reactivity in stable patients after renal transplantation during in vivo high dose immunosuppression. Tapering of the immunosuppressive load had no rebound effect on the donor-specific reactivity, while it allowed recovery of the response to nominal antigens.

Background: The optimum method for inguinal hernia repair has not yet been determined. The recurrence rate for non-mesh methods varies between 0.2 and 33 per cent. The value of tension-free repair with prosthetic mesh remains to be confirmed. The aim of this study was to compare mesh and non-mesh suture repair of primary inguinal hernias with respect to clinical outcome, quality of life and cost in a multicentre randomized trial in general hospitals., Methods: Between September 1993 and January 1996, all patients scheduled for repair of a unilateral primary inguinal hernia were randomized to non-mesh or mesh repair. The patients were followed up at 1 week and at 1, 6, 12, 18, 24 and 36 months. Clinical outcome, quality of life and costs were registered., Results: Three hundred patients were randomized of whom 11 were excluded. Three-year recurrence rates differed significantly: 7 per cent for non-mesh repair (n = 143) and 1 per cent for mesh repair (n = 146) (P = 0.009). There were no differences in clinical variables, quality of life and costs., Conclusion: Mesh repair of primary inguinal hernia repair is superior to non-mesh repair with regard to hernia recurrence and is cost-effective. Postoperative complications, pain and quality of life did not differ between groups.