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Background Minimally invasive liver surgery (MILS) has been progressively adopted on a nationwide scale. The aim of this study is to investigate MILS implementation in a high-volume Dutch hepato-pancreato-biliary and transplant center, which is considered a moderate to low-volume center from a European standpoint. Methods All patients who underwent MILS at Erasmus Medical Center between April 2010 and December 2021 were retrospectively reviewed. Patients’ surgical outcomes were compared after stratification according to resections’ difficulty and liver cirrhosis. Results A total of 212 cases were included. Major liver resections were performed in 24 patients (11%), while minor resections were performed in 188 patients (89%). Among those, 177 (94%) resections were classified as technically minor and 11 (6%) as technically major. Major morbidity was reported in 14/177 patients (8%) after technically minor resections and in 3/24 patients (13%) after major resections. Anatomically and technically major resections had higher intraoperative blood losses (425 (0–2100) vs. 240 (50–110) vs. 100 (0–2400) mL; p-value p-value Conclusion MILS program implementation can lead to encouraging surgical outcomes even in low- to moderate-volume centers. Although low procedural volume might be predictive of impaired outcomes, long-standing experience in the HPB and liver transplant field could mitigate low-case volume effects on surgical outcomes.

Objective: To determine the nationwide implementation and surgical outcome of minor and major robotic liver surgery (RLS) and assess the first phase of implementation of RLS during the learning curve. Background: RLS may be a valuable alternative to laparoscopic liver surgery. Nationwide population-based studies with data on implementation and outcome of RLS are lacking. Methods: Multicenter retrospective cohort study including consecutive patients who underwent RLS for all indications in 9 Dutch centers (August 2014-March 2021). Data on all liver resections were obtained from the mandatory nationwide Dutch Hepato Biliary Audit (DHBA) including data from all 27 centers for liver surgery in the Netherlands. Outcomes were stratified for minor, technically major, and anatomically major RLS. Learning curve effect was assessed using cumulative sum analysis for blood loss. Results: Of 9437 liver resections, 400 were RLS (4.2%) procedures including 207 minor (52.2%), 141 technically major (35.3%), and 52 anatomically major (13%). The nationwide use of RLS increased from 0.2% in 2014 to 11.9% in 2020. The proportion of RLS among all minimally invasive liver resections increased from 2% to 28%. Median blood loss was 150 mL (interquartile range 50-350 mL] and the conversion rate 6.3% (n=25). The rate of Clavien-Dindo grade ≥III complications was 7.0% (n=27), median length of hospital stay 4 days (interquartile range 2-5) and 30-day/in-hospital mortality 0.8% (n=3). The R0 resection rate was 83.2% (n=263). Cumulative sum analysis for blood loss found a learning curve of at least 33 major RLS procedures. Conclusions: The nationwide use of RLS in the Netherlands has increased rapidly with currently one-tenth of all liver resections and one-fourth of all minimally invasive liver resections being performed robotically. Although surgical outcomes of RLS in selected patient seem favorable, future prospective studies should determine its added value.

Background: Despite a lack of high-level evidence, current guidelines recommend laparoscopic left lateral sectionectomy (LLLS) as the routine approach over open LLS (OLLS). Randomized studies and propensity score matched studies on LLLS vs OLLS for all indications, including malignancy, are lacking.Methods: This international multicenter propensity score matched retrospective cohort study included consecutive patients undergoing LLLS or OLLS in six centers from three European countries (January 2000-December 2016). Propensity scores were calculated based on nine preoperative variables and LLLS and OLLS were matched in a 1:1 ratio. Short-term operative outcomes were compared using paired tests.Results: A total of 560 patients were included. Out of 200 LLLS, 139 could be matched to 139 OLLS. After matching, baseline characteristics were well balanced. LLLS was associated with shorter operative time (144 (110-200) vs 199 (138-283) minutes, P < 0.001), less blood loss (100 (50-300) vs 350 (100-750) mL, P = 0.005) and a 3-day shorter postoperative hospital stay (4 (3-7) vs 7 (5-9) days, P < 0.001).Conclusion: This international multicenter propensity score matched study confirms the superiority of LLLS over OLLS based on shorter postoperative hospital stay, operative time, and less blood loss thus validating current guideline advice.

Background Few studies have investigated the learning curves of minimally invasive donor nephrectomy (MIDN) using the cumulative sum (CUSUM) analysis. In addition, no study has compared the learning curves of the different surgical MIDN techniques in one cohort study using the CUSUM analysis. This study aims to evaluate and compare learning curves for several MIDN using the CUSUM analysis. Methods A retrospective review of consecutive donors, who underwent MIDN between 1997 and 2019, was conducted. Three laparoscopic-assisted techniques were applied in our institution and included for analysis: laparoscopic (LDN), hand-assisted retroperitoneoscopic (HARP), and robot-assisted laparoscopic (RADN) donor nephrectomy. The outcomes were compared based on surgeon volume to develop learning curves for the operative time per surgeon. Results Out of 1895 MIDN, 1365 (72.0%) were LDN, 427 (22.5%) were HARP, and 103 (5.4%) were RADN. The median operative time and median blood loss were 179 (IQR, 139–230) minutes and 100 (IQR, 40–200) mL, respectively. The incidence of major complication was 1.2% with no mortality, and the median hospital stay was three (IQR, 3–4) days. The CUSUM analysis resulted in learning curves, defined by decreased operative time, of 23 cases in LDN, 45 cases in HARP, and 26 cases in RADN. Conclusions Our study shows different learning curves in three MIDN techniques with equal post-operative complications. The LDN and RADN learning curves are shorter than that of the hand-assisted donor nephrectomy. Our observations can be helpful for informing the development of teaching requirements for fellows to be trained in MIDN.

Background & Aims: TIGIT is a co-inhibitory receptor, and its suitability as a target for cancer immunotherapy in HCC is unknown. PD1 blockade is clinically effective in about 20% of advanced HCC patients. Here we aim to determine whether co-blockade of TIGIT/PD1 has added value to restore functionality of HCC tumor-infiltrating T cells (TILs). Methods: Mononuclear leukocytes were isolated from tumors, paired tumor-free liver tissues (TFL) and peripheral blood of HCC patients, and used for flow cytometric phenotyping and functional assays. CD3/CD28 T-cell stimulation and antigen-specific assays were used to study the ex vivo effects of TIGIT/PD1 single or dual blockade on T-cell functions. Results: TIGIT was enriched, whereas its co-stimulatory counterpart CD226 was down-regulated on PD1high CD8+ TILs. PD1high TIGIT+ CD8+ TILs co-expressed exhaustion markers TIM3 and LAG3 and demonstrated higher TOX expression. Furthermore, this subset showed decreased capacity to produce IFN-γ and TNF-α. Expression of TIGIT-ligand CD155 was up-regulated on tumor cells compared with hepatocytes in TFL. Whereas single PD1 blockade preferentially enhanced ex vivo functions of CD8+ TILs from tumors with PD1high CD8+ TILs (high PD1 expressers), co-blockade of TIGIT and PD1 improved proliferation and cytokine production of CD8+ TILs from tumors enriched for PD1int CD8+ TILs (low PD1 expressers). Importantly, ex vivo co-blockade of TIGIT/PD1 improved proliferation, cytokine production, and cytotoxicity of CD8+ TILs compared with single PD1 blockade. Conclusions: Ex vivo, co-blockade of TIGIT/PD1 improves functionality of CD8+ TILs that do not respond to single PD1 blockade. Therefore co-blockade of TIGIT/PD1 could be a promising immune therapeutic strategy for HCC patients.

Background The purpose of this study was to evaluate surgical outcomes of kidney transplantation (KTX) based on surgeon volume and surgeon experience, and to develop the learning curve model for KTX using the cumulative sum (CUSUM) analysis. Methods A retrospective review of 1466 consecutive recipients who underwent KTX between 2010 and 2017 was conducted. In total, 51 surgeons, including certified transplant surgeons, transplant fellows and surgical residents were involved in these procedures using a standardized protocol. Outcomes were compared based on surgeon volume (low [1–30] versus high [31≥] volume) and surgeon's type (consultant surgeons, fellows or residents). Results Operative time (129 versus 135 min, P < 0.001) and warm ischemia time (20.9 versus 24.2 min, P < 0.001) were significantly shorter in the high-volume group, however postoperative outcomes were equal in both groups. The CUSUM analysis revealed that approximately 30 procedures were necessary to improve surgical skills. In addition, no effect of surgeon's type including consultant surgeons, fellows and residents on postoperative outcomes was found. Conclusions Surgical training in KTX using a standardize protocol can be accomplished with a steep learning curve without compromising perioperative outcomes under the careful selection of surgeons and procedures.

Background Several difficulty grading systems have been developed as a useful tool for selecting patients and training surgeons in laparoscopic procedures. However, there is little information on predicting the difficulty of laparoscopic donor nephrectomy (LDN). The aim of this study was to develop a grading system to predict the difficulty of LDN. Methods Data of 1741 living donors, who underwent pure or hand-assisted LDN between 1994 and 2018 were analyzed. Multivariable analyses were performed to identify factors associated with prolonged operative time, defined as a difficulty index with 0 to 8. The difficulty of LDN was classified into three levels based on the difficulty index. Results Multivariable analyses identified that male (odds ratio [OR] 1.69, 95% CI 1.37–2.09, P 28 (OR 1.36, 95% CI 1.08–1.72, P = 0.009), pure LDN (OR 1.99, 95% CI 1.53–2.60, P P P P P P = 0.04) and the intermediate difficulty group (3.0%, P = 0.27). No significant difference in major complications was found between the groups. Conclusion We developed a novel grading system with simple preoperative donor factors to predict the difficulty of LDN. This grading system may help surgeons in patient selection to advance their experiences and/or teach fellows from simple to difficult LDN.

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs < 50 mm compared to HCAs ≥ 50 mm. Changes in final postoperative diagnosis were assessed. We performed a retrospective study that included patients who underwent resection for (suspected) HCAs in the Netherlands from 2014 to 2019. Indication for resection was analyzed and stratified for small (50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size

Background: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale. Methods: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume. Results: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0–13%, mortality

Background: Data on surgical outcomes of laparoscopic liver resection (LLR) versus open liver resection (OLR) of benign liver tumour (BLT) are scarce. This study aimed to provide a nationwide overview of postoperative outcomes after LLR and OLR of BLT. Methods: This was a nationwide retrospective study including all patients who underwent liver resection for hepatocellular adenoma, haemangioma and focal nodular hyperplasia in the Netherlands from 2014 to 2019. Propensity score matching (PSM) was applied to compare 30-day overall and major morbidity and 30-day mortality after OLR and LLR. Results: In total, 415 patients underwent BLT resection of whom 230 (55.4%) underwent LLR. PSM for OLR and LLR resulted in 250 matched patients. Median (IQR) length of stay was shorter after LLR than OLR (4 versus 6 days, 5.0–8.0, p < 0.001). Postoperative 30-day overall morbidity was lower after LLR than OLR (12.0% vs. 22.4%, p = 0.043). LLR was associated with reduced 30-day overall morbidity in multivariable analysis (aOR:0.46, CI:0.22–0.95, p = 0.043). Both 30-day major morbidity and 30-day mortality were not different. Conclusions: LLR for BLT is associated with shorter hospital stay and reduced overall morbidity and is preferred if technically feasible.

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use. The considered outcomes and patient- reported outcome measures were generated from systematic literature reviews. Feedback was sought from patients and health professionals. Patients with very high-risk CKD (stages G3a/A3 and G3b/A2- G5, including dialysis, kidney transplantation, and conservative care) were selected as the target population. Using an online modified Delphi process, outcomes important to all patients were selected, such as survival and hospitalization, and to treatment-specific subgroups, such as vascular access survival and kidney allograft survival. Patient-reported outcome measures were included to capture domains of health-related quality of life, which were rated as the most important outcomes by patients. Demographic and clinical variables were identified to be used as case-mix adjusters. Use of these consensus recommendations could enable institutions to monitor, compare, and improve the quality of their CKD care.

Background Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. Method An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. Results A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P Conclusion High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Background & Aims TIGIT is a co-inhibitory receptor, and its suitability as a target for cancer immunotherapy in HCC is unknown. PD1 blockade is clinically effective in about 20% of advanced HCC patients. Here we aim to determine whether co-blockade of TIGIT/PD1 has added value to restore functionality of HCC tumor-infiltrating T cells (TILs). Methods Mononuclear leukocytes were isolated from tumors, paired tumor-free liver tissues (TFL) and peripheral blood of HCC patients, and used for flow cytometric phenotyping and functional assays. CD3/CD28 T-cell stimulation and antigen-specific assays were used to study the ex vivo effects of TIGIT/PD1 single or dual blockade on T-cell functions. Results TIGIT was enriched, whereas its co-stimulatory counterpart CD226 was down-regulated on PD1high CD8+ TILs. PD1high TIGIT+ CD8+ TILs co-expressed exhaustion markers TIM3 and LAG3 and demonstrated higher TOX expression. Furthermore, this subset showed decreased capacity to produce IFN-γ and TNF-α. Expression of TIGIT-ligand CD155 was up-regulated on tumor cells compared with hepatocytes in TFL. Whereas single PD1 blockade preferentially enhanced ex vivo functions of CD8+ TILs from tumors with PD1high CD8+ TILs (high PD1 expressers), co-blockade of TIGIT and PD1 improved proliferation and cytokine production of CD8+ TILs from tumors enriched for PD1int CD8+ TILs (low PD1 expressers). Importantly, ex vivo co-blockade of TIGIT/PD1 improved proliferation, cytokine production, and cytotoxicity of CD8+ TILs compared with single PD1 blockade. Conclusions Ex vivo, co-blockade of TIGIT/PD1 improves functionality of CD8+ TILs that do not respond to single PD1 blockade. Therefore co-blockade of TIGIT/PD1 could be a promising immune therapeutic strategy for HCC patients., Graphical abstract

The presence of hepatocellular adenoma (HCA) in pregnant women requires special consideration, as it has been reported to carry the risk of growth and clinically significant haemorrhage. In this prospective study we assessed aspects of growth of HCA5 cm during pregnancy.This was a multicentre prospective cohort study in pregnant women with suspected HCA5 cm on imaging. Definitive HCA diagnosis was established by MRI with hepatobiliary contrast agents (LCE-MRI), preferably before pregnancy. If at study inclusion a definitive diagnosis was lacking, LCE-MRI was performed after giving birth. Growth of the adenoma (defined as an increase of20%) was closely monitored with ultrasound examinations throughout pregnancy.Of the 66 women included, 18 were excluded from analysis because postpartum LCE-MRI did not confirm the diagnosis of HCA and showed the lesion to be focal nodular hyperplasia. The remaining 48 women, with an HCA confirmed by LCE-MRI, were followed during 51 pregnancies. Median age was 30 years (IQR 27-33) and median body mass index 31.9 kg/mThis study suggests that an HCA5 cm confers minimal risk to a pregnant woman and none to her child. HCA increased in size during a quarter of pregnancies, so we recommend close monitoring with ultrasound examinations, enabling intervention if needed. In light of the large proportion of misdiagnosed HCA, LCE-MRI should be performed to prevent unnecessary anxiety in women with a benign liver lesion.The presence of hepatocellular adenoma in pregnant women requires special consideration, as it carries the risk of growth and haemorrhage. In this study we followed 48 patients with hepatocellular adenoma5 cm during 51 pregnancies and found that a hepatocellular adenoma during pregnancy confers minimal risk to the pregnant woman and none to her child.

__Background__ There are 2 endoscopic surgical techniques that implement 3-dimensional (3D) vision to overcome visual misperception: 3D endoscopy and the da Vinci surgical system. 3D endoscopy has several advantages, such as the presence of tactile feedback and easy implementation, at lower costs. We aimed to assess whether 3D endoscopy could be an alternative to the robot during living donor nephrectomy. __Methods__ Between April 2015 and April 2016, we prospectively collected data on 40 patients undergoing 3D endoscopic living donor nephrectomies in 1 center, performed by a da Vinci-certified surgeon. Data on donors' perioperative results and recipient and graft survival were collected. These data were compared to 40 robot-assisted donor nephrectomies performed in the same center (between January 2012 and May 2014). __Results__ Baseline characteristics for both groups were comparable. Intraoperative results showed a significantly shorter median skin-to-skin time of 138.5 minutes (125.8-163.8) versus 169.0 (141.5-209.8) minutes in favor of the 3D group (P = 0.001). Warm ischemia time (P = 0.003) and hilar phase for both single (1 artery and vein) and multiple anatomies (≥1 artery and/or vein [P = 0.002 and P = 0.010, respectively]) were also significantly reduced in favor of the 3D group, with a flat learning curve. Follow-up demonstrated no readmissions nor significant differences for donors, recipients, and graft survival. __Conclusions__ 3D endoscopy may be a good alternative to robot-assisted donor nephrectomy because morbidity, graft, and recipient survival were comparable, with a significantly shorter median skin-to-skin time, warm ischemia time, and hilar dissection phase. Furthermore, implementation was easy and at lower costs, whereas tactile feedback was preserved.

__Aim__ To identify patient and lesion characteristics associated with the occurrence of single or multiple hepatocellular adenoma (HCA). __Patients and methods__ Using a tertiary centre database, we retrospectively collected information on patient and lesion characteristics, management and follow-up of all patients with HCA included between 2001 and 2016. Patients were classified into three groups; patients with a single HCA, 2-9 HCA and at least 10 HCA. __Results__ A total of 458 patients were diagnosed with HCA, including 121 (26.4%) with single HCA, 235 (51.3%) with 2-9 HCA and 102 (22.3%) with at least 10 HCA. Significant differences in the mean BMI were found, with the highest BMI in patients with more than 10 HCA (P

The role of ureteral stents in living-donor kidney transplantation remains uncertain. In this randomized controlled trial (SPLINT), we compared urological complications in living-donor kidney transplantations performed with or without stents. We included 200 consecutive patients that received living-donor kidney transplantations at the Erasmus MC, University Medical Center, Rotterdam. Patients (124 males, 76 females, mean age 54 ± 13) were randomized for suprapubic externalized single J stents (N = 100) or no stent (N = 100). The primary outcome was the probability of a percutaneous nephrostomy insertion (PCN) during a 12-month follow-up. To assess whether no stenting is noninferior to stenting, we allowed the probability of a PCN to increase by at most 5% (this is the noninferiority margin). Baseline characteristics were comparable between groups. In the no-stent group, there were more PCN insertions, 14% (95% CI 4.3–23.7%); urinary leakages, 12% (95% CI 5.4–21.3%); and surgical re-interventions because of urological complications, 8% (95% CI 1.5–14.5%). The stent group had more hematuria, 26% (95% CI 13.1–38.9%); and graft rejections, 15% (95% CI 2.7–27.3%). Patients in both groups had similar mean GFRs at several time points. Besides a better Euro-Qol-5D in the no-stent group at 2 and 6 weeks postoperative, similar quality of life was reported based on SF-36 and Euro-Qol-5D scores. In this trial, noninferiority has not been demonstrated for no-stent placement in relation to the number urological complications.

Background: Kidney re-transplantation is a relevant option for patients who are returning to dialysis after graft failure. However, evidence is lacking to what extend a third kidney transplantation in the ipsilateral iliac fossa is safe and effective. The aim of this study was to investigate the outcomes of third kidney transplantations in the ipsilateral iliac fossa compared to first and second ipsilateral fossa kidney transplantations. Material/Methods: There were 2074 kidneys transplanted at the Erasmus MC Rotterdam and at the University Medical Centre Groningen. Donor, recipient, and surgical data were collected. The cohort was divided into 3 groups: recipients of a first graft (I KTx; n=1744), recipients of a second graft (II KTx; n=44), and recipients of a third graft (III KTx; n=7). Results: Recipients from the II KTx group had a significantly higher rate of primary non-function (PNF) compared to recipients in the I KTx group and recipients in the III KTx group (4.5% versus 0.7% and 0% respectively; P=0.006). The 1-year graft survival did not differ between groups: 96% for I KTx, 91% for II KTx, and 85% for III KTx (P=0.214). The 5-year graft survival did differ significantly between groups: 89% for I KTx, 82% for II KTx, and 68% for III KTx (P=0.029). There were no differences regards hospital stay and rate of complications between groups. Conclusions: Third kidney transplantation in the ipsilateral iliac fossa is feasible and viable. Short-term results are comparable to the first and the second kidney transplantation, however, long-term results are inferior but acceptable compared to dialysis.

BACKGROUND The aim of this study was to evaluate the number of urinary tract infections (UTI) that occur after kidney transplantation (KT) and to identify possible risk factors for development of a UTI. MATERIAL AND METHODS We retrospectively analyzed all KTs performed between January 2012 and December 2013 in the Erasmus University Medical Center, Rotterdam. UTI was scored if: (1) a patient had a urine culture with no more than 2 species of microorganisms, (2) at least 1 of which was a bacterium of ≥10^5 CFU/mL, (3) which was treated with antibiotics, and (4) which occurred within 3 months after KT. RESULTS A total of 417 patients were transplanted from January 2012 until December 2013. A UTI developed in 115 (28%), after a median of 13 days from transplantation (range: 3-82 days). The most common causative agent was Escherichia coli, followed by Enterococcus faecalis, Enterococcus faecium, and Klebsiella pneumoniae. The variables that were independently related to a UTI were female gender (OR 3.58, 95%CI 2.16-5.91), recipients age >60 y (OR 2.12, 95%CI 1.28-3.48), percutaneous nephrostomy placements (OR 6.29, 95%CI 3.35-11.85), and surgical re-interventions (OR 2.12, 95%CI 1.04-4.32). Mean glomerular filtration rate was significantly lower in the group of patients with a UTI at 3, 6, 9, and 12 months postoperatively compared to those patients who did not have a UTI. CONCLUSIONS We conclude that a UTI after KT is a common problem. We identified independent risk factors for the development of a UTI. UTI is associated with a GFR decrease postoperatively.

Novel systemic treatments for hepatocellular carcinoma (HCC) are strongly needed. Immunotherapy is a promising strategy that can induce specific antitumor immune responses. Understanding the mechanisms of immune resistance by HCC is crucial for development of suitable immunotherapeutics. We used immunohistochemistry on tissue-microarrays to examine the co-expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM and IDO, as well as tumor CD8(+) lymphocyte infiltration in HCC, in two independent cohorts of patients. We found that at least some expression in tumor cells was seen in 97% of cases for HVEM, 83% for PD-L1, 79% for Gal-9 and 66% for IDO. In the discovery cohort (n = 94), we found that lack of, or low, tumor expression of PD-L1 (p

Contains fulltext : 138363.pdf (Publisher’s version ) (Closed access) BACKGROUND: The worldwide introduction of multimodal enhanced recovery programs has also changed perioperative care in patients who undergo liver resection. This study was performed to assess current perioperative practice in liver surgery in 11 European HPB centers and compare it to enhanced recovery after surgery (ERAS) principles. METHODS: In each unit, 15 consecutive patients (N = 165) who underwent hepatectomy between 2010 and 2012 were retrospectively analyzed. Compliance was classified as "full," "partial," or "poor" whenever >/= 80, >/= 50, or

Urological complications after kidney transplantation are mostly related to the ureteroneocystostomy leading to significant morbidity, mortality, and high costs. The most commonly used techniques for the ureteroneocystostomy are the intravesical and the extravesical anastomosis. No evidence in favor of one of these two anastomoses exists. Our aim was to determine the technique with the best outcome regarding urological complications in a prospective randomized controlled trial (Netherlands Trial Register NTR2320). We randomized 200 consecutive recipients of a living donor kidney for either an intravesical or an extravesical anastomosis. The primary outcome was defined as placement of a percutaneous nephrostomy. No significant differences were found in the number of percutaneous nephrostomy placements or ureter reinterventions between both groups. Nevertheless, significantly fewer urinary tract infections occurred in the group with an extravesical anastomosis. In addition, this anastomosis was performed significantly faster compared with the intravesical anastomosis. Thus, extravesical ureteroneocystostomy was associated with significantly fewer urinary tract infections and might be preferable because of its surgical simplicity.

Hepatocellular adenoma (HCA) is a rare, benign liver tumor. Discovery of this tumor is usually as an incidental finding, correlated with the use of oral contraceptives, or pregnancy. Treatment options have focused on conservative management for the straightforward, smaller lesions (5 cm) that pose a greater risk of hemorrhage or malignant progression. In recent years, a new molecular subclassification of HCA has been proposed, associated with characteristic morphological features and loss or increased expression of immunohistochemical markers. This subclassification could possibly provide considerable benefits in terms of patient stratification, and the selection of treatment options. In this review we discuss the decision-making processes and associated risk analyses that should be made based on lesion size, and subtype. The usefulness of this subclassification system in terms of the procedures instigated as part of the diagnostic work-up of a suspected HCA will be outlined, and suitable treatment schemes proposed.

Purpose: To study the short- and long-term outcomes of kidney transplantation in patients with a bladder augmentation or urinary diversion compared to patients with a kidney transplantation in a normal functional bladder. Patients and methods: Between January 2000 and March 2011, 13 patients received 16 grafts into a reconstructed urinary tract. We performed a retrospective case-control study and matched each patient to 4 controls for donor and recipient gender and year of transplantation. Results: Short- and long-term complications of kidney transplantation occurred in 12 patients, varying from urinary tract infections to medical hospitalization with or without surgical or radiological intervention. In 5 patients, a percutaneous nephrostomy (PCN) was placed followed by surgical re-intervention. In three patients, the grafts failed as a result of chronic rejection and were re-transplanted. There was no graft loss as a result of surgical complications or the reconstructed urinary tract. One-year patient and graft survival was 100 %. After five years, all patients were alive and seven of nine grafts (77.8 %) were functioning. Mean follow-up time was 4.3 years. Among the controls, 55 grafts were transplanted in 52 patients. Ten patients received a PCN. Five patients needed surgical re-intervention. In three patients, transplantectomy was performed for ongoing rejection. Three patients were re-transplanted. One patient had a failing graft 7.5 years post-transplantation and became dialysis dependent. Conclusion: Kidney transplantation in patients with a reconstructed urinary tract has an increased complication rate. Nevertheless, the long-term results are comparable to patients with a normal urinary bladder.

Urological complications are still a major problem postoperatively with a reported incidence of up to 30%, associated with significant morbidity, mortality, prolonged hospital stay and high medical costs. To date, there is no evidence favouring either an extravesical or an intravesical approach. The purpose of this systematic review and meta-analysis is to determine if an intravesical or extravesical anastomosis in kidney transplantation is to be preferred. Comprehensive searches were conducted in PubMed, Embase and the Cochrane Library. Reference lists were searched manually. The methodology was in accordance with the PRISMA statement. Two randomized controlled trials and seventeen cohort studies were identified. Based on the meta-analysis, outcome was in favour of the extravesical anastomosis. A relative risk (RR) for stenosis of 0.67 (confidence interval (CI), 0.48-0.93; p = 0.02), for leakage 0.55 (CI 0.39-0.80; p = 0.001) for the total number of urological complications 0.56 (CI 0.41-0.76; p < 0.001) and for haematuria of 0.41 (CI 0.22-0.76; p = 0.005) was demonstrated. Based on our results, we conclude that there is evidence in favour of the extravesical ureteroneocystostomy for having a smaller amount of urological complications in kidney transplantation.

The aim of this study was to evaluate the effects of 2 types of external ureteral stents on the number of urological complications after kidney transplant.Data were retrospectively collected from 366 consecutive transplants performed between January 2013 and January 2015 in our hospital, in which an external ureteral stent was placed during surgery and removed after 9 days. Urological complications were defined as urinary leakage or ureteral stenosis requiring percutaneous nephrostomy placement.A total of 197 patients received a straight stent with 2 larger side holes (type A; 8F "Covidien" tube; Covidien, Dublin, Ireland) and 169 patients received a single J stent with 7 smaller side holes (type B; 7F "Teleflex" single J stent; Teleflex Medical, Athlone, Ireland). We found a significantly higher number of percutaneous nephrostomy placements with type A stents, with 34 (17%) versus 16 (9%) in type B (P = .030). Reason for percutaneous nephrostomy placement, occurrence of stent dysfunction, and need for early removal (8 days) were equal in both groups (P = .397), whereas incidence of rejection and urinary tract infection were higher in type B stent group. Patient and graft survival did not differ between the groups.Use of the type B stent was associated with less urological complications compared with the type A stent.

We present the first case report of chylous ascites following total robot-assisted donor nephrectomy. A 39-year-old female underwent a transperitoneal left-sided total robot-assisted donor nephrectomy. The procedure was uneventful and the patient was discharged without any symptoms. At postoperative Day 29, the patient presented with abdominal pain, nausea and a distended, painful abdomen with shifting dullness. She was diagnosed with chylous ascites by ultrasonography and puncture analysis, and treated with therapeutic drainage and dietary restriction. After 4 weeks, she was free of symptoms. The occurrence of this complication is rare after donor nephrectomy. Fortunately, the complication can be successfully treated within a few weeks with minimal discomfort for the patient as demonstrated in this case. It is of utmost importance to minimize the risks and limit discomfort for live kidney donors who willingly undergo major surgery to improve the well-being of another individual.

Background Whether vascular multiplicity should be considered as contraindication and therefore ‘extended donor criterion’ is still under debate. Methods Data from all live kidney donors from 2006–2013 (n = 951) was retrospectively reviewed. Vascular anatomy as imaged by MRA, CTA or other modalities was compared with intraoperative findings. Furthermore, the influence of vascular multiplicity on outcome of donors and recipients was studied. Results In 237 out of 951 donors (25%), vascular multiplicity was present. CTA had the highest accuracy levels regarding vascular anatomy assessment. Regarding outcome of donors with vascular multiplicity, warm ischemia time (WIT) and skin-to-skin time were significantly longer if arterial multiplicity (AM) was present (5.1 vs. 4.0 mins and 202 vs. 178 mins). Skin-to-skin time was significantly longer, and complication rates were higher in donors with venous multiplicity (203 vs. 180 mins and 17.2% vs. 8.4%). Outcome of renal transplant recipients showed a significantly increased WIT (30 vs. 26.7 minutes), higher rate of DGF (13.9% vs. 6.9%) and lower rate of BPAR (6.9% vs. 13.9%) in patients receiving a kidney with AM compared to kidneys with singular anatomy. Conclusions We conclude that vascular multiplicity should not be a contra-indication, since it has little impact on clinical outcome in the donor as well as in renal transplant recipients.

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.

Purpose: To investigate the correlation between magnetic resonance (MR) imaging findings and pathologic subtype classification of hepatocellular adenoma (HCA). Materials and Methods: This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. MR imaging studies of 61 lesions (48 patients; median age, 36 years) were available and were independently reviewed by two radiologists. Consensus readings on all morphologic and signal-intensity imaging features were obtained. Previously, these lesions had been classified on the basis of pathologic findings and immunohistochemical analysis. Fisher exact and chi(2) tests were performed to compare the results between the different subtypes. A Bonferroni correction was applied to correct for multiple testing (alpha < .0033). Results: MR imaging signs of diffuse intratumoral fat deposition were present in seven (78%) of nine liver-fatty acid binding protein (L-FABP)-negative HCAs compared with five (17%) of 29 inflammatory HCAs (P = .001). Steatosis within the nontumoral liver was present in 11 (38%) of 29 inflammatory HCAs compared with none of the L-FABP-negative HCAs (P = .038). A characteristic atoll sign was only seen in the inflammatory group (P = .027). Presence of a typical vaguely defined type of scar was seen in five (71%) of seven beta-catenin-positive HCAs (P = .003). No specific MR imaging features were identified for the unclassified cases. Conclusion: L-FABP-negative, inflammatory, and beta-catenin-positive HCAs were related to MR imaging signs of diffuse intratumoral fat deposition, an atoll sign, and a typical vaguely defined scar, respectively. Since beta-catenin-positive HCAs are considered premalignant, closer follow-up with MR imaging or resection may be preferred.

The safety of older live kidney donors, especially the decline in glomerular filtration rate (GFR) after donation, has been debated. In this study we evaluated long-term renal outcome in older live kidney donors. From 1994 to 2006 follow-up data of 539 consecutive live kidney donations were prospectively collected, during yearly visits to the outpatient clinic. Donors were categorized into two groups, based on age: < 60 (n = 422) and >= 60 (n = 117). Elderly had lower GFR predonation (80 vs. 96 mL/min respectively, p < 0.001). During median follow-up of 5.5 years, maximum decline in eGFR was 38% +/- 9% and the percentage maximum decline was not different in both groups. On long-term follow-up, significantly more elderly had an eGFR < 60 mL/min (131 (80%) vs. 94 (31%), p < 0.001). However, renal function was stable and no eGFR of less than 30 mL/min was seen. In multivariate analysis higher body mass index (HR 1.09, 95%CI 1.03-1.14) and more HLA mismatches (HR 1.17, 95%CI 1.03-1.34) were significantly correlated with worse graft survival. Donor age did not influence graft survival. After kidney donation decline in eGFR is similar in younger and older donors. As kidney function does not progressively decline, live kidney donation by elderly is considered safe.

Purpose: To investigate the safety and efficacy of radiofrequency (RF) ablation for the treatment of hepatocellular adenoma (HCA). Materials and Methods: From 2000 to 2009, 170 patients with HCA were referred to a single tertiary hepatobiliary center. Medical records of 18 patients treated with RF ablation were retrospectively analyzed. Results: All patients were female, and the majority had a history of hormonal contraceptive use. Ten patients (56%) had multiple HCAs, with a median number of two lesions (range, one to 12) per patient. Median size of HCA at the time of RF ablation was 3.0 cm (range, 0.8-7.3 cm). A total of 45 HCAs were ablated in 32 sessions (open, n = 4; percutaneous, n = 28). RF ablation was complete after the first session in 26 HCAs (57.8%), and the majority of patients underwent multiple RF ablation sessions to fully ablate all HCAs. Major complications developed in two patients. Conclusions: RF ablation can be used effectively in the treatment of HCA. However, multiple sessions are often required, and signs of residual adenoma might persist in some patients despite repetitive treatment. RF ablation might be especially beneficial in cases not amenable to surgery or in patients who would require major hepatic resection otherwise.

Background & Aims: Hepatocellular adenoma in pregnant women requires special considerations because of the risk of hormone induced growth and rupture. To prevent these potential lethal complications, pregnancy is either often discouraged or the surgical resection of large adenomas is recommended. It may be questioned whether it is justified to deny a young woman a pregnancy, as the biological behaviour of hepatocellular adenoma may be less threatening than presumed. In this study we establish the management of hepatocellular adenoma during pregnancy based on our own experience and literature. Methods: Twelve women with documented hepatocellular adenoma were closely monitored during a total of 17 pregnancies between 2000 and 2009. Their files were reviewed. Results: In four cases, hepatocellular adenomas grew during pregnancy, requiring a Caesarean section in one patient (two pregnancies) at 36 and 34 weeks.because of an assumed high risk of rupture. In one case radiofrequency ablation therapy was applied in the first trimester to treat a hormone sensitive hepatocellular adenoma, thereby excluding potential growth later in pregnancy. No intervention was performed in the other 14 cases and all pregnancies had an uneventful course with a successful maternal and fetal outcome. Conclusions: A "wait and see" management may be advocated in pregnant women presenting with a hepatocellular adenoma. In women with large tumours or in whom hepatocellular adenoma had complicated previous pregnancies, surgical resection may be recommended. In women with smaller adenomas it may no longer be necessary to discourage pregnancy. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

P>Laparoscopic donor nephrectomy (LDN) is less traumatic and painful than the open approach, with shorter convalescence time. Hand-assisted retroperitoneoscopic (HARP) donor nephrectomy may have benefits, particularly in left-sided nephrectomy, including shorter operation and warm-ischemia time (WIT) and improved safety. We evaluated outcomes of HARP alongside LDN. From July 2006 to May 2008, 20 left-sided HARP procedures and 40 left-sided LDNs were performed. Intra and postoperative data were prospectively collected and analysis on outcome of both techniques was performed. More female patients underwent HARP compared to LDN (75% vs. 40%, P = 0.017). Other baseline characteristics were not significantly different. Median operation time and WIT were shorter in HARP (180 vs. 225 min, P = 0.002 and 3 vs. 5 min, P = 0.007 respectively). Blood loss did not differ (200 ml vs.150 ml, P = 0.39). Intra and postoperative complication rates for HARP and LDN (respectively 10% vs. 25%, P = 0.17 and 5% vs. 15%, P = 0.25) were not significantly different. During median follow-up of 18 months estimated glomerular filtration rates in donors and recipients and graft- and recipient survival did not differ between groups. Hand-assisted retroperitoneoscopic donor nephrectomy reduces operation and warm ischemia times, and provides at least equal safety. Hand-assisted retroperitoneoscopic may be a valuable alternative for left-sided LDN.

To determine the effectiveness, costs, and cost-effectiveness of strategies for the management of hepatocellular adenoma (HA) in women who are otherwise healthy.A Markov model was developed to estimate the quality-adjusted life expectancy (in quality-adjusted life-years [QALYs]), lifetime costs (in 2007 U.S. dollars), and net health benefits (QALY equivalent) of surgery, transarterial embolization (TAE), radiofrequency ablation (RFA), and watchful waiting. Model parameters and their distributions were derived from the literature and the hospital database.In patients with HA tumors suitable for RFA, RFA had the highest effectiveness (23.89 QALYs) and lowest costs ($2965). The treatment decision was sensitive to RFA-related mortality. In patients with tumors unsuitable for RFA, watchful waiting combined with TAE in cases of hemorrhage had the highest effectiveness (23.83 QALYs) and lowest costs ($8493). The treatment decision was sensitive to probability of tumor growth, probability of hemorrhage, and hemorrhage-related mortality.According to the model results, the most favorable treatment strategy for patients with small HAs was RFA. In patients with HA unsuitable for RFA, watchful waiting was the optimal strategy.

Background. The objective was to evaluate the incidence and treatment of incisional hernia after kidney transplantation and to identify potential risk factors. Methods. A retrospective cohort study was performed. All kidney transplant recipients between 2002 and 2012 were included. Two groups were identified: patients with and without incisional hernia. An analysis of risk factors for the development of incisional hernia was performed. Results. A total of 1,564 kidney recipients were included. Fifty patients (3.2%) developed incisional hernia. On univariate analysis, female sex (54 vs 35 %), body mass index (BMI) >30 kg/m(2) (38 vs 17%), concurrent abdominal wall hernia (30 vs 16%), multiple explorations of the ipsilateral iliac fossa (38 vs 19%), left iliac fossa implantation (36 vs 24%), history of smoking (72 vs 57%), and duration of the kidney transplantation procedure (210 vs 188 minutes) were associated with the development of incisional hernia (P30; HR 2.9), multiple explorations of the ipsilateral iliac fossa (HR 2.0), duration of operation (HR 1.007), and concurrent abdominal wall hernia (HR 2.3) were independent risk factors. Twenty-six of 50 patients (52%) underwent operative repair, of whom 9 (35 %) required emergency repair. Conclusion. The incidence of incisional hernia after kidney transplantation with a median follow-up of 59 months is 3.2%. Obesity (BAIT >30), female sex, concurrent abdominal wall hernias, history of smoking, duration of surgery, and multiple explorations were independent risk factors for the development of incisional hernia after kidney transplantation. Attempts at preventing incisional hernias based on these risk factors should be explored.

The aim of this study was to evaluate the role of ureteral length on urological complications. Data were retrospective collected from the INEX-trial database, a RCT to compare the intravesical to the extravesical ureteroneocystostomy. Ureteral length was measured in 198 recipients and used to divide recipients into three categories based on interquartile ranges: short (≤8.5 cm), medium (8.6-10.9 cm) and long ureters (≥11 cm). Urological complications were defined as the number of percutaneous nephrostomy placements (PCN). Fifty recipients fell into the short, 98 into the medium and 50 recipients into the long ureter category. Median follow-up was 26 (range 2-45) months. There was no significant difference in number of PCN placements between the categories. There were 9 (18%) PCN placements in the short ureter category, 21 (20%) in medium ureter category and 10 (21%) in the long ureter category, P = 0.886. Risk factor analysis for gender, arterial multiplicity and type of ureteroneocystostomy showed no differences in PCN placements between the three ureteral length categories. We conclude that ureteral length alone does not seem to influence the number of urological complications.

With the routine use of improved imaging modalities, more benign liver lesions are detected nowadays. An accurate characterization of these incidental lesions may be a challenge, and frequently a biopsy or even unnecessary surgery is being performed. However, these interventions are not always to the benefit of the patient.A Medline search of studies relevant to imaging diagnosis and management of the most common, benign, solid and non-solid liver lesions was undertaken. References from identified articles were handsearched for further relevant articles. The authors' own experiences with benign liver lesions were also taken into account.Although atypical imaging features are the exception rather than the rule, it is sometimes difficult to differentiate between benign and malignant lesions, and knowledge of their imaging features is essential if unnecessary work-up is to be avoided. The use of tissue-specific contrast media, which has clearly improved the accuracy of highly advanced radiological techniques, may be helpful during differential diagnosis. Once having established an accurate diagnosis, surgery is rarely indicated for a benign liver lesion because of its asymptomatic nature.Knowledge of imaging features and a clear management strategy during diagnostic work-up, emphasizing the indications for surgery, will minimize the number of patients who have to undergo biopsy or unnecessary surgery.