Transarterial chemoembolization of hepatocellular carcinoma before liver transplantation and risk of post-transplant vascular complications: a multicentre observational cohort and propensity score-matched analysis.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular cancer (HCC) on the waiting list for liver transplantation may be associated with an increased risk for hepatic artery complications. The present study aims to assess the risk for, primarily, intraoperative technical hepatic artery problems and, secondarily, postoperative hepatic artery complications encountered in patients who received TACE before liver transplantation. METHODS: Available data from HCC liver transplantation recipients across six European centres from January 2007 to December 2018 were analysed in a 1 : 1 propensity score-matched cohort (TACE versus no TACE). Incidences of intraoperative hepatic artery interventions and postoperative hepatic artery complications were compared. RESULTS: Data on postoperative hepatic artery complications were available in all 876 patients (425 patients with TACE and 451 patients without TACE). Fifty-eight (6.6 per cent) patients experienced postoperative hepatic artery complications. In total 253 patients who had undergone TACE could be matched to controls. In the matched cohort TACE was not associated with a composite of hepatic artery complications (OR 1.73, 95 per cent c.i. 0.82 to 3.63, P = 0.149). Data on intraoperative hepatic artery interventions were available in 825 patients (422 patients with TACE and 403 without TACE). Intraoperative hepatic artery interventions were necessary in 69 (8.4 per cent) patients. In the matched cohort TACE was not associated with an increased incidence of intraoperative hepatic artery interventions (OR 0.94, 95 per cent c.i. 0.49 to 1.83, P = 0.870). CONCLUSION: In otherwise matched patients with HCC intended for liver transplantation, TACE treatment before transplantation was not associated with higher risk of technical vascular issues or hepatic artery complications.

Lay Summary Patients with liver cancer may be treated with transarterial chemoembolization (TACE) during the period on the transplant waiting list. With TACE, chemotherapeutic coils are injected directly into the small arteries supplying the tumour, after which these vessels are closed. The aim of this therapy is to decrease the tumour size and slow down tumour growth. However, concerns are raised that manipulation of the main hepatic artery by TACE may cause damage to the artery itself. If this would result in problems during or after liver transplantation when the artery is connected to the artery supplying the donor liver, this may endanger the donor liver graft survival. The present study shows no increased risk in problems to connect the artery during liver transplantation after TACE treatment. Also, arterial complications after liver transplantation did not occur more frequently if patients had received TACE treatment. The authors therefore conclude that TACE treatment before liver transplantation could be considered a safe approach.

Conservative treatment versus elective repair of umbilical hernia in patients with liver cirrhosis and ascites: results of a randomized controlled trial (CRUCIAL trial).

PURPOSE: To establish optimal management of patients with an umbilical hernia complicated by liver cirrhosis and ascites. METHODS: Patients with an umbilical hernia and liver cirrhosis and ascites were randomly assigned to receive either elective repair or conservative treatment. The primary endpoint was overall morbidity related to the umbilical hernia or its treatment after 24 months of follow-up. Secondary endpoints included the severity of these hernia-related complications, quality of life, and cumulative hernia recurrence rate. RESULTS: Thirty-four patients were included in the study. Sixteen patients were randomly assigned to elective repair and 18 to conservative treatment. After 24 months, 8 patients (50%) assigned to elective repair compared to 14 patients (77.8%) assigned to conservative treatment had a complication related to the umbilical hernia or its repair. A recurrent hernia was reported in 16.7% of patients who underwent repair. For the secondary endpoint, quality of life through the physical (PCS) and mental component score (MCS) showed no significant differences between groups at 12 months of follow-up (mean difference PCS 11.95, 95% CI - 0.87 to 24.77; MCS 10.04, 95% CI - 2.78 to 22.86). CONCLUSION: This trial could not show a relevant difference in overall morbidity after 24 months of follow-up in favor of elective umbilical hernia repair, because of the limited number of patients included. However, elective repair of umbilical hernia in patients with liver cirrhosis and ascites appears feasible, nudging its implementation into daily practice further, particularly for patients experiencing complaints. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01421550, on 23 August 2011.

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area.

BACKGROUND: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. METHODS: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. RESULTS: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018). CONCLUSIONS: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment.

Molecular dynamics study of the melting of a supported 887-atom Pd decahedron.

We employ classical molecular dynamics simulations to investigate the melting behaviour of a decahedral Pd(887) cluster on a single layer of graphite (graphene). The interaction between Pd atoms is modelled with an embedded-atom potential, while the adhesion of Pd atoms to the substrate is approximated with a Lennard-Jones potential. We find that the decahedral structure persists at temperatures close to the melting point, but that just below the melting transition, the cluster accommodates to the substrate by means of complete melting and then recrystallization into an fcc structure. These structural changes are in qualitative agreement with recently proposed models, and they verify the existence of an energy barrier preventing softly deposited clusters from 'wetting' the substrate at temperatures below the melting point.

Evidence for a size-dependent transition between noncrystalline structures and crystalline structures with defects in frozen Lennard-Jones clusters.

Liquid Lennard-Jones clusters of 14 different sizes from N=55-923 atoms were cooled down in Monte Carlo simulations (40 runs for each size) to the reduced temperature T* = 0.05 . Structural analysis and visualization were applied for classification of the internal structure of all 560 final clusters. Small clusters revealed the presence of the multishell icosahedra or regular polyicosahedra. In larger clusters, beginning from N=309 , the noncrystalline atom ordering is often replaced by the formation of defected crystalline clusters in the form of layered face-centered cubic-hexagonal close-packed (fcc-hcp) clusters or defected layered clusters with some additional nonparallel hcp overlayers. The presence of regular polyicosahedral clusters, relatively numerous even at the largest analyzed sizes, is attributed to kinetic effects in structure formation.

['Will I receive a liver transplant in time?'; chance of survival of patients on the liver transplant waiting list]. / 'Komt mijn nieuwe lever wel op tijd?'.

OBJECTIVE: To calculate the chance of receiving a liver transplant for patients on the liver transplant waiting list in the Netherlands. DESIGN: Retrospective cohort research. METHOD: Data of all patients in the Netherlands on the waiting list for liver transplantation, from the introduction of the model of end-stage liver disease score on 16th December 2006 through to 31st December 2013 were collected. Survival analysis was computed with competing risk analyses. RESULTS: A total of 851 patients were listed, of whom 236 patients with hepatocellular carcinoma, 147 patients with primary sclerosing cholangitis, 142 patients with post-alcoholic liver disease, 93 patients with metabolic liver disease, 78 with viral hepatitis and 155 patients listed for other indications. The median waiting time till transplantation was 196 days. The chance to be transplanted at two years from listing was 65% and the risk of death was 17%. Patients with metabolic liver disease had the highest chance of undergoing liver transplantation. Patients with viral hepatitis were at highest risk of death while on the list, as well as having the lowest chance of undergoing liver transplantation. CONCLUSION: Our study shows a 65% chance of getting transplanted in time after a median waiting time of 6 months in the Netherlands. Sadly, 1 in 6 patients die before liver transplantation can be performed, with the highest risk of death occurring in patients with viral hepatitis.

Pretransplant Immune Interplay Between Donor and Recipient Influences Posttransplant Kidney Allograft Function.

BACKGROUND: Renal transplant candidates present immune dysregulation caused by chronic uremia, and deceased kidney donors present immune activation induced by brain death. Pretransplant donor and recipient immune-related gene expression were examined in the search for novel predictive biomarkers crosslinking recipient and donor pretransplant immune status with transplant outcome. MATERIALS AND METHODS: This study included 33 low-risk consecutive renal transplant recipients and matched deceased donors. The expression of 29 genes linked to tissue injury, T-cell activation, cell migration, and apoptosis were assessed in postreperfusion kidney biopsies, as well as 14 genes in pretransplant peripheral blood of the kidney recipients. Gene expression was analyzed with real-time polymerase chain reaction on custom-designed low-density arrays. RESULTS: Donor MMP9 expression was related to delayed graft function occurrence (P = .036) and short term kidney allograft function (14th day rs = -0.44, P = .012; 1st month rs = -0.46, P = .013). Donor TGFB1 expression was associated with short- and long-term graft function (14th day rs = -0.47, P = .007; 3rd month rs = -0.63, P = .001; 6th month rs = -0.52, P = .010; 12th month rs = -0.45, P = .028; 24th month rs = -0.64, P = .003). Donor TGFB1 expression was not related to donor age (rs = 0.32, P = .081), which was also an independent factor influencing the outcome. Recipient gene expression was not related to graft function but determined the acute rejection risk. Recipient IFNG and, to a lesser extent, IL18 expression were protective against acute rejection (area under the curve [AUC] 0.84, P < .001, and AUC 0.79, P < .001, respectively). CONCLUSION: Kidney transplant outcome depends on the interplay between donor-related immune factors, which mostly affect allograft function and recipient immune milieu, influencing an alloreactive response.

Favorable resolution of hepatic infarctions in transplanted liver after portal vein thrombosis treated by surgical thrombectomy: a case report.

Portal vein thrombosis (PVT) after orthotopic liver transplantation (OLT) is a life-threatening complication associated with a high rate of graft loss and patient death, with reported incidence of 1% to 2% in adults. We report a case of an early PVT after OLT complicated by hepatic infarctions in the liver graft. After surgical thrombectomy and restoration of the portal inflow, hepatic infarctions resolved spontaneously within 6 months, which was confirmed by computed tomography.

Predictive value of Banff score of early kidney allograft biopsies for 1-year graft survival.

The aim of this study was to evaluate the Banff score of early kidney allograft biopsies, taken during the first month after transplantation, seeking an association between early rejection and acute tubular necrosis. We analyzed data from 71 patients transplanted between 2000 and 2004 who had renal allograft biopsies performed within the first posttransplant month (23 women, 48 men), ages 18 to 67 years. All biopsies performed in cases of delayed or deteriorated graft function were graded according to the Banff' 97 classification. Twelve months after transplantation, 19 patients exhibited excellent renal function (group 1, serum creatinine concentration [Scr] < or = 1.5 mg/dL); 25 patients demonstrated preserved renal function (group II, Scr 1.51-1.99 mg/dL); and 19 patients showed deteriorated renal function (group III, Scr > or = 2.0 mg/dL). Eight recipients lost their grafts within 1 year after transplantation (group IV). The Banff index was defined as a sum of all components (value of glomerulitis ["g"] + interstitial inflammation ["i"] + tubulitis ["t"] + arteriolar hyaline thickening ["ah"] + intimal arteritis ["v"]). The deterioration of renal function was associated with a higher Banff index; patients who lost their grafts showed the highest values of this index. Scores of "v," "ah," and Banff index were positively correlated with serum creatinine concentrations at 28, 90, 180, and 360 days (P < .05). Glomerulitis ("g") was correlated with creatinine concentrations at 90 and 360 days (P < .05). Tubulitis ("t") and interstitial inflammation ("i") displayed no association with renal function at any time.

Incidence and outcome of transplant renal artery stenosis: single center experience.

Since the incidence of transplant renal artery stenosis (TRAS) in renal allografts varies from 1% to 23%, we sought to examine its incidence, to analyze treatment options, and to ascertain its outcomes. Retrospective analysis of 793 kidney allograft recipients transplanted between 1996 and 2004 revealed an incidence of 0.9% (n = 7). Time from kidney transplantation to the first symptoms varied from 1 week to 3 years (median, 4 months). Three patients experiences refractory hypertension and six patients developed allograft dysfunction. Screening color Doppler ultrasonography showed hemodynamic changes in six patients with the definitive diagnosis confirmed by angiography in all patients. One patient with an anastomotic stenosis was treated with a surgical operation and six patients, percutaneous transluminal angioplasty (PTA), with stenting in three cases. Both surgical as well as PTA treatment were successful in all but one patient, who underwent PTA alone, developed chronic renal insufficiency necessitating hemodialysis and finally lost his allograft. In the other patients all symptoms resolved after treatment and the patients are doing well with functioning allografts. Although TRAS was an uncommon complication, if recognized promptly it could be treated by surgery or PTA with a high success rate.

Development of the IFJ single ion hit facility for cell irradiation.

In recent years, a single ion hit facility has been constructed at the IFJ ion microprobe. The setup is used for the precise irradiations of living cells by a controlled number of ions. Investigations of such type have two very important requirements: (1) cells must be examined in their natural state and environment (i.e. without previously being killed, preferentially neither fixed nor stained) and (2) the possibility of automatic irradiation of large number of cells (including computer recognition of cells positions) must be provided. This work presents some of the crucial features of the off-line and on-line optical systems, including self-developed software responsible for automatic cell recognition.

Activity of glutathione S-transferases in the urine of kidney transplant recipients during the first week after transplantation.

UNLABELLED: Glutathione S-Tranferases (GST) are the enzymes which are strictly specific for epithelial cells of the proximal and distal tubules in the kidney. These enzymes are detected in the urine when some tubular damage process is found. In healthy people urine GST is hardly detected. The goal of this study was to evaluate the release of two isoenzymes -- alpha and pi GST in the urine of kidney graft recipients during the first week after kidney transplantation, aiming to differentiate the cause of the delayed function (DF) of transplanted kidney. MATERIAL AND METHODS: 50 cadaveric kidneys were procured using standard technique with "in situ" cooling using UW solution. All kidneys were machine perfused. After preservation kidneys were transplanted to 50 ERSD patients. Standard triple drug immunosuppression was applied (steroids, CsA, Cell-Cept or Aza.). Graft function and the release of alpha and pi GST in the urine were measured 1, 3 and 7 days after transplantation. RESULTS: immediate function (IF) was found in 72% (36pts), DF in 28% (14pts). 5 of DF patients had ATN, 4 had acute rejection (REJ) and the remaining 5 had ATN and acute rejection (see table below). CONCLUSIONS: High alpha and pi GST concentrations were found in pts with DF graft function during the first 7 days after Tx. Elevated pi GST and low alpha GST in the urine indicates acute rejection. High alpha and pi GST in pts with DF should raise suspicion of graft rejection.

Vascular complications after the treatment with Ilizarov external fixators.

Iatrogenic vascular injuries from external fixation in orthopaedics and traumatology are frequent. Three cases of vascular injuries after the treatment with Ilizarov external fixators were treated at our institution. These include two cases of pseudoaneurysms and one case of acute ischaemia of the lower limb. Two patients became symptomatic only after removal of the fixator. In all cases, the diagnosis was made by color flow duplex sonography. All vascular injuries needed surgical repair.

[The differences in liver regenerative rate after partial hepatectomy in rats treated wtih selected immunosuppressants]. / Róznice w stopniu odrostu watroby w zaleznosci od stosowanego leku immunosupresyjnego u szczurów po czesciowej hepatektomii.

The aim of this study was to assess the influence of selected immunosuppressants on liver regeneration. In fifty experiments were performed on fifty male Buffalo strain rats, 12 weeks old and weighing between 206 and 266 grams. Partial hepatectomy (2/3) was carried out under ether anaesthesia. Rats were randomly assigned to one of six groups (10 rats per group) and treated orally as follows: group 1--without immunosuppressant (control group), group 2--ciclosporin A (CyA) 10 mg/kg/day, group 3--azathioprine (Aza) 3 mg/kg/day, group 4--tacrolimus (Tac) 0.1 mg/kg/day and group 5--prednisolone (Pred) 1 mg/kg/day. After 42 days observation all rats were killed. Resected liver tissue was weighed at the day of operation and also the remnant liver was weighed after sacrification of the animal. The regenerative rate was obtained by dividing the wet weight of the remaining liver by the estimated preoperative weight of the whole liver and multiplying by 100. Regenerative rate of liver tissue was significantly higher in rats treated with CyA and Tac and significantly lower in rats treated with Pred. There were no significant differences between control group and rats treated with Aza. This study has shown that among immunosupressant used in experiment only CyA and Tac stimulated liver regeneration after partial hepatectomy. On the other hand only Pred inhibited liver regeneration, whereas Aza had no influence on liver restoration.

[Surgical treatment of primary liver cysts. Personal experience]. / Leczenie chirurgiczne pierwotnych torbieli watroby. Doswiadczenia wlasne.

Nonparasitic liver cysts are diagnosed more often now. The aim of this study was to report the authors' experience with treatment for nonparasitic liver cysts. Retrospective review of medical records of 25 patients with hepatic cyst between 1990 and 1999 was undertaken to determine optimal treatment. Polycystic liver disease (PLCD) occurred in 2 patients and remaining patients had a simple liver cyst. In eight patients liver cyst were diagnosed incidentally and 17 patients were symptomatic. Twenty one patients underwent operations: 9 open deroofing, 5 liver resection (2 segmentectomies and 3 nonanatomical), 4 cyst excision, one case of laparoscopic fenestration and in 2 cases open drainage in infected liver cyst were performed. Four patients with asymptomatic, small (< 2 cm) hepatic cyst had no operative procedures--they were observed with ultrasonography control every six months. There were no perisurgical deaths. The symptomatic recurrence occurred in one patients (4.7%). The complications rate was low (4.7%)--the patient with PLCD had liver abscess and the open drainage were performed. Open surgery is safe and effective for symptomatic liver cyst and complication rate is low. Small and asymptomatic liver cysts should be followed up under ultrasonographic examination.

[The management in vascular trauma of extremities]. / Postepowanie w urazach naczyniowych konczyn.

Between 1990-1998 in the Department of Vascular Surgery, Medical Academy in Wroclaw, 104 patients were operated due to artery trauma: 28 women, 76 men. Mean age was 37 years. In 58 cases acute ischaemia occurred, in 46--haemorrhage. Preoperative procedure consisted of preparation and diagnostics, in some cases angiography. Predominantly autogenous material was used for artery reconstruction. In 25 cases prosthetic grafts were implanted. In 53 patients (79.1%) good results were obtained, complications occurred in 14 cases (20.9%).

[Radioisotopic diagnosis of infected anastomotic groin aneurysms after complications with aorto-bifemoral vascular prosthesis]. / Diagnostyka radioizotopowa tetniaków zespoleniowych w pachwinie po zabiegach wszczepienia protezy aortalno-dwuudowej.

UNLABELLED: Between 1990 and 1996 at the Department of Vascular Surgery, Medical Academy in Wroclaw 34 patients with groin aneurysms were operated. All patients had aorto-bifemoral graft implantation before. The age range between 41 and 81 years. Among patients there were 4 women and 30 men. The diagnosis of groin aneurysm was based on physical and ultrasound examination. In each case scintigraphy with 99Tc labeled leukocytes was performed. Scintigraphic picture showed graft infection in eight (23.5%) patients (group I). In 26 (76.5%) cases (group II) there was no infection on scintigraphy. In group I all patients were operated-the infected graft was excised and then implantation of straight PTFE or venous by-pass "in situ" was performed. In group II all patient were also operated, but through the groin approach only -in 9 cases reconstruction of the anastomosis between graft and artery was done and in 17 cases PTFE by-pass was performed. In group I the results of the treatment were good in 6 cases; in remaining two patients the amputation of the leg had to be done. In group II the results of the operation was good in 24 cases and 2 patients had amputation of the leg. CONCLUSION: Scintigraphy with 99Tc labeled leukocytes is beneficial in the diagnosis of infected groin aneurysms after previous vascular reconstruction.

[Comparison of peritoneal patch and vascular prosthesis monitored with isotopes and parameters of humoral and cell mediated response]. / Porównanie zachowania sie otrzewnej sciennej oraz protezy naczyniowej w ukladzie tetniczym, monitorowane badaniami izotopowymi oraz badaniami odpowiedzi humoralnej i komórkowej organizmu.

The aim of this experimental study was to assess the reaction of peritoneal patch and vascular graft after implantation in arterial system. We compare complement haemolytic activation CH-50%, serum elastase and scintigraphy using Tc99 labeled leukocytes. There were significant differences in parameters of humoral and cell-mediated response between implantation of peritoneal patch and vascular graft. Twelve months later histological examination was made to determine healing processes of implanted materials. The results of this study are encouraging and confirm benefits of peritoneal patch in vascular surgery creating a new possibilities of angioplasty.

[Early cellular and humoral response after vascular prosthesis implantation in the arterial system]. / Wczesna odpowiedz komórkowa i humoralna po wszczepieniu protezy naczyniowej w uklad tetniczy.

The aim of the study was to determine the level of leukocytes activation after the implantation of vascular graft. As an experimental model we used 20 dogs. The aorto-iliac unilateral graft (dacron 6 mm) was implanted to all animals. The adhesion and migration of the leukocytes was estimated postoperatively by scintigraphy using Tc99 labeled leukocytes. The increased migration and adhesion was found in both proximal and distal anastomoses till the 30th postoperative day and it was more intensive in the distal anastomosis.

[Clinical evaluation of a polyester vascular prosthesis impregnated with albumins from material of the Vascular Surgical Clinic AM in Wroclaw in the years 1994-1997. Introductory report]. / Ocena kliniczna poliestrowej impregnowanej albuminami protezy naczyniowej w materiale Kliniki Chirurgii Naczyniowej AM we Wroclawiu w latach 1994-1997. Doniesienie wstepne.

The aim of this work was clinical evaluation of impregnated (albumins) prostheses of Polish production. Those prostheses were compared with polyester knitted vascular prostheses. We evaluated a group of 48 patients to whom prostheses covered with albumins were implanted and 52 patients to whom nonimpregnated prosthesis was implanted in 1994-1997. The prostheses were implanted in aortofemoral segment. The achieved results prove the good quality of the impregnated prosthesis and its high value for vascular reconstructive surgery.