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Objectives: Acoustic radiation force impulse (ARFI) quantification estimates tissue elasticity by measuring shear-wave velocity (SWV) and has been applied to various organs. We evaluated the impact of variations in the transducer force applied to the skin on the SWV ultrasound measurements in kidney transplant cortex and ARFI's ability to detect fibrosis in kidney transplants.Methods: SWV measurements were performed in the cortex of 31 patients with kidney allografts referred for surveillance biopsies. A mechanical device held the transducer and applied forces were equal to a compression weight of 22, 275, 490, 975, 2,040 and 2,990 g.Results: SWV group means were significantly different by repeat measures ANOVA [F(2.85,85.91) = 84.75, P < 0.0005 for 22, 275, 490, 975 and 2,040 g compression weight] and also by pairwise comparisons. Biopsy specimens were sufficient for histological evaluation in 29 of 31 patients. Twelve had grade 0, 11 grade 1, five grade 2 and one grade 3 fibrosis. One-way ANOVA showed no difference in SWV performed with any of the applied transducer forces between grafts with various degrees of fibrosis.Conclusion: SWV measurements in kidney transplants are dependent on the applied transducer force and do not differ in grafts with different grades of fibrosis.Key Points: • Acoustic radiation force impulses (ARFI) can quantify tissue elasticity during ultrasound examinations. • Elasticity estimated by ARFI in kidney transplants depends on applied transducer force. • ARFI quantification cannot detect renal allograft fibrosis. • ARFI elasticity estimates may in general vary with applied transducer force. [ABSTRACT FROM AUTHOR]

Background: Chronic allograft nephropathy (CAN) characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. The diagnosis can currently only be verified by a graft biopsy. Purpose: To evaluate whether non-invasive dynamic color Doppler sonographic parenchymal perfusion measurements are different in grafts with various degrees of biopsy proven renal transplant fibrosis. Material and Methods: Forty-nine adult patients were prospectively included. Four patients were excluded. Color Doppler videos from the renal cortex were recorded. Perfusion in the renal cortex was evaluated using a software package which calculates color pixel area and flow velocity, encoded by each pixel inside a region of interest of a video sequence. The software calculates parameters that describe tissue perfusion numerically. Two of these, the perfusion intensity and tissue pulsatility index, were compared to grade of interstitial fibrosis (0-3) in biopsies. Observer agreement was evaluated in a subset of 12 patients. Results: Of the 45 patients analyzed, 18 patients had grade 0, 18 had grade 1, seven had grade 2 and two had grade 3 fibrosis. The mean perfusion intensity of grade 0 was significantly higher than that of grade 2 and 3 fibrosis in the proximal cortical layer (1.65 m/s vs. 0.84 m/s, P = 0.008). No significant difference was found between grade 0 and grade 1 fibrosis. Perfusion intensity was correlated to estimated glomerular filtration rate (Pearson r 0.51, P = 0.001, R(2) = 0.26 and 0.46, P = 0.001, R(2) = 0.22 in the distal and proximal cortex, respectively). Inter-observer agreement of the perfusion intensity, expressed as intraclass correlation coefficient was 0.69 in the proximal part of the cortex. Intra-observer agreement was 0.85 for observer 1 and 0.82 for observer 2. Conclusion: Perfusion intensity assessed by dynamic color Doppler measurements is significantly reduced in allografts with grade 2 and 3 fibrosis compared to allografts without fibrosis. Further studies involving longitudinal assessment of allografts undergoing protocol biopsies would be of interest. [ABSTRACT FROM AUTHOR]

Objectives: Total tumor volume (TTV) is associated with overall and recurrence-free survival in patients with colorectal cancer liver metastases (CRLM). However, the labor-intensive nature of such manual assessments has hampered the clinical adoption of TTV as an imaging biomarker. This study aimed to develop and externally evaluate a CRLM auto-segmentation model on CT scans, to facilitate the clinical adoption of TTV., Methods: We developed an auto-segmentation model to segment CRLM using 783 contrast-enhanced portal venous phase CTs (CT-PVP) of 373 patients. We used a self-learning setup whereby we first trained a teacher model on 99 manually segmented CT-PVPs from three radiologists. The teacher model was then used to segment CRLM in the remaining 663 CT-PVPs for training the student model. We used the DICE score and the intraclass correlation coefficient (ICC) to compare the student model's segmentations and the TTV obtained from these segmentations to those obtained from the merged segmentations. We evaluated the student model in an external test set of 50 CT-PVPs from 35 patients from the Oslo University Hospital and an internal test set of 21 CT-PVPs from 10 patients from the Amsterdam University Medical Centers., Results: The model reached a mean DICE score of 0.85 (IQR: 0.05) and 0.83 (IQR: 0.10) on the internal and external test sets, respectively. The ICC between the segmented volumes from the student model and from the merged segmentations was 0.97 on both test sets., Conclusion: The developed colorectal cancer liver metastases auto-segmentation model achieved a high DICE score and near-perfect agreement for assessing TTV., Critical Relevance Statement: AI model segments colorectal liver metastases on CT with high performance on two test sets. Accurate segmentation of colorectal liver metastases could facilitate the clinical adoption of total tumor volume as an imaging biomarker for prognosis and treatment response monitoring., Key Points: Developed colorectal liver metastases segmentation model to facilitate total tumor volume assessment. Model achieved high performance on internal and external test sets. Model can improve prognostic stratification and treatment planning for colorectal liver metastases., Competing Interests: Declarations. Ethics approval and consent to participate: The Medical Ethics Review Committee of the Amsterdam UMC, the Regional Ethical Committee of Norway, and the Data Protection Officer of Oslo University Hospital approved this study protocol. All patients were managed per institutional practices. All patients signed a written informed consent form permitting the use of their data for studies. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT., Methods: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039., Findings: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0])., Interpretation: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging., Funding: The Dutch Cancer Society and Bayer AG - Pharmaceuticals., Competing Interests: Declaration of interests BE received honoraria from Medtronic for lectures. KH has a leadership role in the Dutch Colorectal Cancer group. DJL received honoraria from Intuitive surgical. MMa received support for travel to attend the following courses where she gave lectures: ECIO 2023, ESGAR Liver Imaging workshop, and Alimentary tract cancer course New York 2023. MMe received grants from Medtronic–Covidien, Johnson & Johnson, Immunophotonics, and Angiodynamics. MMe also received consulting fees from Angiodynamics and Medtronic–Covidien; honoraria from Medtronic–Covidien, Johnson & Johnson, and Angiodynamics; and support for attending meetings from Angiodynamics. MMe is participating in the Data Safety and Monitoring Board of the Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma trial and had leadership or fiduciary roles in the Society of Interventional Oncology, CIRSE & ECIO, and CVIR. ÅAF received honoraria from Bayer AG, Olympus Healthcare, and Siemens Healthineers. JS received funding from the Dutch Cancer Society (grant number 11916) and is president-elect of the European Society of Gastrointestinal and Abdominal Radiology. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The aim of the present study is to report on the ability of metabolic tumor volume (MTV) of liver metastases from pre-transplant 18 F-FDG PET/CT in combination with conventional radiological measurements from CT scans to predict long-term disease-free survival (DFS), overall survival (OS), and survival after relapse (SAR) after liver transplantation for colorectal liver metastases. The total liver MTV was obtained from the 18 F-FDG PET/CT, and the size of the largest metastasis and the total number of metastases were obtained from the CT. DFS, OS, and SAR for patients with a low and high MTV, in combination with a low and high size, number, and tumor burden score, were compared using the Kaplan-Meier method and log-rank test. Patients with a low number of metastases and low MTV had a significantly longer OS than those with a high MTV, with a median survival of 151 vs. 26 months ( p = 0.010). Patients with a high number of metastases and low MTV had significantly longer DFS, OS, and SAR than patients with a high MTV ( p = 0.034, 0.006, and 0.026). The tumor burden score of group/zone 3, in combination with a low MTV, had a significantly improved DFS, OS, and SAR compared to those with a high MTV ( p = 0.034, <0.001, and 0.006). Patients with a low MTV of liver metastases had a long DFS, OS, and SAR despite a high number of liver metastases and a high tumor burden score.

Importance: Liver transplant for colorectal cancer with liver metastases was abandoned in the 1990s due to poor overall survival. From 2006, liver transplant for in nonresectable colorectal liver metastases has been reexamined through different prospective trials., Objective: To determine predictive factors for transplant long-term survival and cure after liver transplant., Design, Setting, and Participants: This was a prospective, nonrandomized controlled cohort study derived from different clinical trials on liver transplant for colorectal liver metastases from 2006 to 2020 at Oslo University Hospital. The trials differed in prognostic inclusion criteria, but the design was otherwise identical regarding follow-up scheme to determine disease recurrence, overall survival, and survival after relapse. Final data analysis was performed on December 31, 2021. All patients with colorectal liver metastases from comparable prospective liver transplant studies were included., Exposure: Liver transplant., Main Outcomes and Measures: Disease-free survival, overall survival, and survival time after recurrence were determined in all participants., Results: A total of 61 patients (median [range] age, 57.8 [28.7-71.1] years; 35 male [57.4%]) underwent liver transplant at Oslo University Hospital. Posttransplant observation time ranged from 16 to 165 months, and no patient was lost to follow-up. Median disease-free period, overall survival, and survival after relapse were 11.8 (95% CI, 9.3-14.2) months, 60.3 (95% CI, 44.3-76.4) months, and 37.1 (95% CI, 4.6-69.5) months, respectively. Negative predictive factors for overall survival included the following: largest tumor size greater than 5.5 cm (median OS, 25.3 months; 95% CI, 15.8-34.8 months; P <.001), progressive disease while receiving chemotherapy (median OS, 39.8 months; 95% CI, 28.8-50.7 months; P = .02), plasma carcinoembryonic antigen values greater than 80 μg/L (median OS, 26.6 months; 95% CI, 22.7-30.6 months; P <.001), liver metabolic tumor volume on positron emission tomography of greater than 70 cm3 (26.6 months; 95% CI, 11.8-41.5 months; P <.001), primary tumor in the ascending colon (17.9 months; 95% CI, 0-37.5 months; P <.001), tumor burden score of 9 or higher (23.3 months; 95% CI, 19.2-27.4 months; P = .02), and 9 or more liver lesions (42.5 months; 95% CI, 17.2-67.8 months; P = .02). An Oslo score of 0 or Fong Clinical Risk Score of 1 yielded 10-year survival of 88.9% and 80.0%, respectively., Conclusions and Relevance: Results of this nonrandomized controlled trial suggest that selected patients with liver-only metastases and favorable pretransplant prognostic scoring had long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care.

Objective: To report 15 years of experience with metabolic tumor volume (MTV) of liver metastases from the preoperative 18 F-FDG PET/CT to predict long-term survival after liver transplantation (LT) for unresectable colorectal liver metastases (CRLM)., Methods: The preoperative 18 F-FDG PET/CT from all SECA 1 and 2 patients was evaluated. MTV was obtained from all liver metastases. The patients were divided into one group with low MTV (< 70 cm 3 ) and one group with high MTV (> 70 cm 3 ) based on a receiver operating characteristic analysis. Overall survival (OS), disease-free survival (DFS) and post recurrence survival (PRS) for patients with low versus high MTV were compared using the Kaplan-Meier method and log rank test. Clinopathological features between the two groups were compared by a nonparametric Mann-Whitney U test for continuous and Fishers exact test for categorical data., Results: At total of 40 patients were included. Patients with low MTV had significantly longer OS (p < 0.001), DFS (p < 0.001) and PRS (p = 0.006) compared to patients with high values. The patients with high MTV had higher CEA levels, number of liver metastases, size of the largest liver metastasis, N-stage, number of chemotherapy lines and more frequently progression of disease at LT compared to the patients with low MTV., Conclusion: MTV of liver metastases is highly predictive of long-term OS, DFS and PRS after LT for unresectable CRLM and should be implemented in risk stratification prior to LT., (© 2022. The Author(s).)

The objective of the study was to determine the impact of PET uptake on liver metastases on overall survival (OS) after resection of pulmonary metastases in patients who had received liver transplantation (LT) due to unresectable colorectal liver-only metastases. Resection of pulmonary colorectal metastases is controversial. Some hospitals offer this treatment to selected patients, whereas other hospitals do not perform the procedure in colorectal cancer patients who develop pulmonary metastases. All patients included in the LT studies who developed pulmonary metastases as first site of relapse, and had resection of these as first treatment, were included in this report. Metabolic tumor volume (MTV) in liver was derived from the pre-transplant PET examinations. OS from time of resection was calculated by the Kaplan−Meier method. Patients with low MTV (<70 cm3) had significantly longer OS from time of resection of pulmonary metastases compared to patients with high MTV (>70 cm3). Patients with low MTV in the liver had 10-year OS from time of pulmonary resections of 86%. Liver MTV values from pre-transplant PET examinations may predict long OS in colorectal cancer patients with a resection of pulmonary metastases developing after LT. Thus, in selected colorectal cancer patients developing pulmonary metastases resection of these metastases should be the treatment of choice.

Liver transplantation (LT) in selected colorectal cancer (CRC) patients with nonresectable liver-only metastases may result in 5-year overall survival of up to about 70-100%. However, the majority will have recurrent disease. All patients included in this report were included in prospective studies. Forty-four out of 56 patients had a relapse, and all 44 patients received treatment for recurrent disease. The organ of the first relapse was lung metastases in 23 of the 44 patients. The first treatment modality of the relapse was the treatment with curative intent in 55.8% of the patients, and chemotherapy was the first treatment administered to 25.6% of the patients. Patients receiving surgery of lung metastases had a 5-year overall survival of 66.5% from the time of metastasectomy. Patients receiving treatment with curative intent for metastases to other organs had a 5-year overall survival of 24.8%. Nine of the 44 patients had no evidence of disease (NED) at the end of the follow-up. Median time of NED in these patients was 54.3 months, and median overall survival from the time of LT was 8.4 years. Because of the high incidence of recurrent disease, these patients should have a systematic long-term follow-up since many of the relapses may be treated with curative intent., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Importance: Portal vein embolization (PVE) has been implemented in patients with extensive colorectal liver metastases to increase the number of patients able to undergo liver resection. Liver transplant could be an alternative in selected patients with extensive liver-only disease, and we have recently shown promising survival outcomes., Objective: To compare overall survival (OS) among patients with colorectal cancer and high liver metastasis tumor load who were treated with liver transplant or with PVE and liver resection., Design, Setting, and Participants: This comparative effectiveness research study assessed 50 patients with colorectal cancer liver metastases who were previously enrolled in liver transplant studies between November 2006 and August 2019 at Oslo University Hospital in Norway. Those patients were compared with a retrospective cohort of 53 patients in the Oslo University Hospital PVE database from March 2006 through November 2015 with similar selection criteria who underwent PVE and liver resection., Main Outcomes and Measures: The OS among patients with high tumor load after liver transplant was compared with that among patients with high tumor load who underwent PVE and liver resection. High tumor load was defined as 9 or more metastatic tumors or a diameter of 5.5 cm or longer for the largest liver lesion., Results: In the PVE cohort of 53 patients, the median age was 61.8 years (range, 34.3-71.3 years), and 36 patients (68%) were men. The 5-year OS rate among 38 patients who underwent liver resection after PVE was 44.6%. The 5-year OS rate for patients with high tumor load was 33.4% for those who underwent liver transplant and 6.7% for those who underwent PVE. Among patients with high tumor load and left-sided primary tumors, the 5-year OS rate was 45.3% for those receiving a liver allograft and 12.5% for those treated with PVE and liver resection., Conclusions and Relevance: Patients with nonresectable disease, an extensive liver tumor load, and left-sided primary tumors had long OS after liver transplant, exceeding the survival outcome for those patients treated with PVE and liver resection.

Objective: To determine overall survival and disease-free survival in selected patients with nonresectable liver-only colorectal cancer receiving liver transplantation., Background: Patients with nonresectable colorectal cancer receiving palliative chemotherapy has a 5-year overall survival of about 10%. Liver transplantation provided an overall survival of 60% in a previous study (SECA-I). Risk factors for death were carcinoembryonic antigen (CEA) >80 μg/L, progressive disease on chemotherapy, size of largest lesion>5.5 cm, and less than 2 years from resection of the primary tumor to transplantation., Methods: In this prospective (SECA-II) study, we included colorectal cancer patients with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography scans and at least 10% response to chemotherapy. Time from diagnosis to liver transplant was required to be more than 1 year., Results: At a median follow-up of 36 months, Kaplan-Meier overall survival at 1, 3, and 5 years were 100%, 83%, and 83%, respectively. Disease-free survival at 1, 2, and 3 years were 53%, 44%, and 35%, respectively. Overall survival from time of relapse at 1, 2, and 4 years were 100%, 73%, and 73%, respectively. Recurrence was mainly slow growing pulmonary metastases amenable to curative resection. Fong Clinical Risk Score of 1 to 2 at the time of diagnosis resulted in longer disease-free survival than score 3 to 4 (P = 0.044). Patients included in the present study had significantly better prognostic factors than the previous SECA-I study., Conclusion: Liver transplantation provides the longest overall survival reported in colorectal cancer patient with nonresectable liver metastases. Improved selection criteria give patients with nonresectable colorectal liver metastases a 5-year overall survival comparable to other indications for liver transplantation.

Patients with nonresectable colorectal cancer receiving palliative chemotherapy have a 5-year overall survival rate of about 10%. Liver transplant provided a Kaplan-Meier-estimated 5-year overall survival of up to 83%. The objective of the study was to evaluate the ability of different scoring systems to predict long-term overall survival after liver transplant. Patients with colorectal cancer with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography (PET)-CT scans from 2 prospective studies (SECA-I and -II) were included. All included patients had previously received chemotherapy. PET-CT was performed within 90 days of the liver transplant. Overall survival, disease-free survival, and survival after relapse based on the Fong Clinical Risk Score, total PET liver uptake (metabolic tumor volume), and Oslo Score were compared. At median follow-up of 85 months for live patients, Kaplan-Meier overall survival rates at 5 years were 100%, 78%, and 67% in patients with Fong Clinical Risk Score 0 to 2, metabolic tumor volume-low group, and Oslo Score 0 to 2, respectively. Median overall survival was 101, 68, and 65 months in patients with Fong Clinical Risk Score 0 to 2, metabolic tumor volume-low, and Oslo Score 0 to 2. These selection criteria may be used to obtain 5-year overall survival rates comparable to other indications for liver transplant., (© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: There is an uncertainty whether total inflammation in early protocol kidney graft biopsies is associated with fibrosis progression. We investigated whether total inflammation, both in fibrotic and non-fibrotic areas, at week 6 would predict fibrosis progression at one yr post-transplant., Methods: We included 156 single adult ABO compatible kidney recipients with adequate week 6 and one yr transplant protocol biopsies (312 biopsies). Biopsies were scored according to the current Banff criteria. In addition, fibrosis and inflammation in fibrotic and non-fibrotic areas were scored in a 10-grade semi-quantitative eyeballing system from 0% to 100%., Results: Fibrosis increased significantly from week 6 to one yr both by the 10-grade scoring system from 0.69 ± 1.07 to 1.45 ± 1.86, (mean ± SD), p < 0.001 and by Banff interstitial fibrosis (ci) scoring 0.81 ± 0.65 to 1.13 ± 0.87, p < 0.001. The 10-grade scoring system detected a larger proportion of fibrosis progressors than the Banff scoring 40.4% vs. 35.5%, p < 0.001. No significant positive association was found between inflammation at week 6 and progression of fibrosis in either of the scoring systems., Conclusions: Total inflammation in kidney transplant biopsies at week 6 did not predict progression of fibrosis at one yr post-transplant., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: There is a need to determine biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC). We evaluated the prognostic utility of the enhanced liver fibrosis (ELF) score in Norwegian PSC patients. Serum samples were available from 305 well-characterized large-duct PSC patients, 96 ulcerative colitis patients, and 100 healthy controls. The PSC patients constituted a derivation panel (recruited 1992-2006 [n = 167]; median age 41 years, 74% male) and a validation panel (recruited 2008-2012 [n = 138]; median age 40 years, 78% male). We used commercial kits to analyze serum levels of hyaluronic acid, tissue inhibitor of metalloproteinases-1, and propeptide of type III procollagen and calculated ELF scores by the previously published algorithm. Results were also validated by analysis of ELF tests using the ADVIA Centaur XP system and its commercially available reagents. We found that PSC patients stratified by ELF score tertiles exhibited significantly different transplant-free survival in both panels (P < 0.001), with higher scores associated with shorter survival, which was confirmed in the validation panel stratified by ELF test tertiles (P = 0.003). The ELF test distinguished between mild and severe disease defined by clinical outcome (transplantation or death) with an area under the curve of 0.81 (95% confidence interval [CI] 0.73-0.87) and optimal cutoff of 10.6 (sensitivity 70.2%, specificity 79.1%). In multivariate Cox regression analysis in both panels, ELF score (hazard ratio = 1.9, 95% CI 1.4-2.5, and 1.5, 95% CI 1.1-2.1, respectively) was associated with transplant-free survival independently of the Mayo risk score (hazard ratio = 1.3, 95% CI 1.1-1.6, and 1.6, 95% CI 1.2-2.1, respectively). The ELF test correlated with ultrasound elastography in separate assessments., Conclusion: The ELF score is a potent prognostic marker in PSC, independent of the Mayo risk score., (© 2015 by the American Association for the Study of Liver Diseases.)

Background: Formation of lymphocele (accumulation of lymphatic fluid) is a common surgical complication following kidney transplantation. This open randomized trial evaluated the effect of prophylactic fenestration on lymphocele formation., Methods: Adult recipients of kidney grafts from deceased donors were randomized to undergo peritoneal fenestration during the transplantation or to standard surgical procedure without fenestration. The incidence of symptomatic lymphocele in the two groups was compared at 1 year after transplantation. A protocol-based ultrasound examination was performed in the 1st, 5th, and 10th postoperative week. Any hypoechoic perirenal collection was registered., Results: One hundred thirty recipients were randomized to peritoneal fenestration (n = 69) or standard therapy (n = 61). Six patients were excluded. Nine of 58 (15.5%) patients in the standard group developed symptomatic lymphoceles requiring treatment during the first postoperative year, versus 2 of 66 (3.0%) in the fenestration group (relative risk = 0.20, 95% confidence interval: 0.04-0.82, P = 0.015). Seven major surgical procedures and five percutaneous drainages due to lymphoceles were performed in the standard group, compared with two percutaneous drainages in the fenestration group. The prevalence of fluid collections in the fifth postoperative week was significantly higher in the standard group (66% vs. 37%; relative risk = 0.57, 95% confidence interval: 0.37-0.71, P = 0.005)., Conclusion: Prophylactic fenestration reduced the risk of lymphoceles and the need for invasive procedures to treat this condition. The results need to be confirmed in a population of transplant recipients on lower steroids and with the use of wound drains.

Chronic allograft nephropathy characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness. We evaluated if the method could reveal renal transplant fibrosis. In a prospective study, 30 adult renal transplant recipients were included. ARFI quantification, given as shear wave velocity (SWV), of the renal cortex was performed by two observers. SWV was compared to grade of fibrosis (0-3) in biopsies. The median SWV was 2.8 m/s (range: 1.6-3.6), 2.6 m/s (range: 1.8-3.5) and 2.5 m/s (range: 1.6-3) for grade 0 (n = 12), 1 (n = 10) and grades 2/3 (n = 8) fibrosis respectively. SWV did not differ significantly in transplants without and with fibrosis (grade 0 vs. grade 1, P = 0.53 and grade 0 vs. grades 2/3, P = 0.11). The mean intraobserver coefficient of variation was 22% for observer 1 and 24% for observer 2. Interobserver agreement, expressed as intraclass correlation coefficient was 0.31 (95% CI: -0.03 to 0.60). This study does not support the use of ARFI quantification to assess low-grade fibrosis in renal transplants. ARFI quantification in its present stage of development has also high intra- and interobserver variation in renal transplants., (© 2010 The Authors. Transplant International © 2010 European Society for Organ Transplantation.)

Serotonin (5-hydroxytryptamine, 5-HT) receptor pre-mRNA is alternatively spliced in human tissue to produce three splice variants, h5-HT7(a), h5-HT7(b) and h5-HT7(d), which differ only in their carboxyl terminal tails. Using membranes from transiently and stably transfected HEK293 cells expressing the three recombinant h5-HT7 splice variants we compared their pharmacological profiles and ability to activate adenylyl cyclase. Using PCR on cDNA derived from various human tissues, the 5-HT7(a) and 5-HT7(b) splice variants were detected in every tissue examined. The h5-HT7(d) splice variant was detected in 13 of 16 tissues examined, with predominant expression in the heart, small intestine, colon, ovary and testis. All three h5-HT7 splice variants displayed high affinity binding for [3H]5-HT (pKd=8.8-8.9) in the presence and absence of 100 microM GTP and had similar binding affinities for all 17 ligands evaluated. In HEK293 cells expressing similar, high levels of receptor (approximately 10,000 fmol/mg protein), 5-CT (5-carboxamidotryptamine), 5-MeOT (5-methoxytryptamine) and 5-HT were full agonists while 8-OH-DPAT ((2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin) was a partial agonist with relative efficacy of approximately 0.8. Even at this high receptor level, EC50 values for stimulation of adenylyl cyclase were 10- to 50-fold higher than the Kd values, indicating a lack of spare receptors. No significant differences in coupling to adenylyl cyclase were observed between the three splice variants over a wide range of receptor expression levels. For antagonists, binding affinities determined by displacement of [3H]5-HT binding and by competitive inhibition of 5-HT-stimulated adenylyl cyclase activity were essentially identical amongst the splice variants. These studies indicate that the three human splice variants are pharmacologically indistinguishable and that modifications of the carboxyl tail do not influence coupling to adenylyl cyclase.

5-Hydroxytryptamine (5-HT) increases human heart rate and atrial contractile force and hastens atrial relaxation through 5-HT4 receptors. Moreover, 5-HT may be arrhythmogenic and give rise to atrial fibrillation. It is not clear which splice variant(s) of the 5-HT4 receptor is expressed and mediates these effects of 5-HT in the human heart. Previous studies have indicated different pharmacological properties of 5-HT4 receptors in human heart and mouse colliculi neurones, possibly due to expression of different splice variants. We therefore cloned the human 5-HT4(b) receptor and compared its pharmacological properties with those of the cloned human 5-HT4(a) receptor and searched for the corresponding mRNA in human tissues. The primary structures of the two human 5-HT4 receptor splice variants are identical except for divergent C-terminal tails of 28 and 29 amino acids in the 5-HT4(a) and 5-HT4(b) receptors, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that both variants were coexpressed in various tissues, including cardiac atrium and ventricle. Additional bands suggested the presence of more than two human 5-HT4 receptor splice variants. With cloned receptors stably expressed in HEK293 cells or transiently expressed in COS-7 cells, [3H]GR 113808 consistently showed slightly higher binding affinity to h5-HT4(b) than to h5-HT4(a) receptor (pKd 0.1-0.2 log units higher). Competition of agonists, partial agonists and antagonists for [3H]GR113808 binding revealed no significant differences between the two receptors. For 5-HT4 receptor agonists and antagonists, their potencies in stimulating or inhibiting, respectively, 5-HT-stimulated adenylyl cyclase activity correlated well with their binding affinities. Tropisetron and SB207710 showed partial agonist activity at high receptor expression levels for both isoforms. Cisapride and renzapride were both partial agonists at moderate receptor levels and full agonists at high receptor levels. Cisapride was more potent than renzapride while the converse was the case in human atrium, for which cisapride had lower affinity and agonist potency than at the recombinant receptors. The binding affinities and agonist potencies of ligands for both 5-HT4(a) and 5-HT4(b) receptors correlated with the corresponding affinities and potencies in human atrium. The agonist potency of SB207710 was around 10 times lower than its binding and blocking affinity for both splice variants, suggesting that activation of adenylyl cyclase and blockade of 5-HT responses are mediated through different conformational states. The similar pharmacological properties of the two human 5-HT4 receptor splice variants together with their expression in human atrium would be consistent with mediation of the cardiostimulant effects of 5-HT through both variants. However, the effects of cisapride appear either mediated through non-a and non-b splice variants of the 5-HT4 receptor or 5-HT4(a) and 5-HT4(b) receptor expression in human atrial cells alters somewhat their pharmacological profile through still unknown mechanisms.