Potential value of EUS in pancreatic surveillance of VHL patients.

BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a head-to-head comparison, we evaluated endoscopic ultrasound (EUS) and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET) compared with conventional screening techniques for early detection of pancreatic solid lesions in VHL patients. METHODS: We conducted a cross-sectional, prospective study in 22 patients at a tertiary care university medical center. Patients with VHL mutation or with one VHL manifestation and a mutation carrier as first-degree family member, with recent screening by abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS), were eligible. Patients underwent EUS by linear Pentax echoendoscope and Hitachi EUB-525, and (11)C-5-HTP PET. Patient-based and lesion-based positivity for pancreatic solid lesions were calculated for all imaging techniques with a composite reference standard. RESULTS: In 10 of the 22 patients, 20 pancreatic solid lesions were detected: 17 with EUS (P < 0.05 vs CT/MRI+ SRS), 3 with (11)C-5-HTP PET, 3 with SRS, 9 with CT/MRI, and 9 with CT/MRI + SRS. EUS evaluations showed solid lesions with a median size of 9.7 mm (range 2.9-55 mm) and most of them were homogeneous, hypoechoic, isoelastic, and hypervascular. Moreover, EUS detected multiple pancreatic cysts in 18 patients with a median of 4 cysts (range 1-30). CONCLUSIONS: EUS is superior to CT/MRI + SRS for detecting pancreatic solid lesions in VHL disease.(11)C-5-HTP PET has no value as a screening method in this setting. EUS performs well in early detection of pNETs, but its role in VHL surveillance is unclear.

Hepatocellular carcinoma in tyrosinemia type 1 without clear increase of AFP.

Patients with hereditary tyrosinemia type 1 have an elevated risk of developing hepatocellular carcinoma, especially if initiation of treatment with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione is delayed. Hepatocellular carcinoma can usually be suspected when there are increased α1-fetoprotein levels and characteristic imaging features. The present case shows that a lack of a clear increase in α1-fetoprotein should still lead to consideration of liver transplantation when imaging features change.

Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic Kidney Disease at Various Levels of Kidney Function.

BACKGROUND: A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR. STUDY DESIGN: Clinical trial with comparisons before and after treatment. SETTING & PARTICIPANTS: Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting. INTERVENTION: Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively). OUTCOMES: Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers). MEASUREMENTS: GFR was measured by (125)I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression. RESULTS: In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron. LIMITATIONS: Limited sample size, no control group. CONCLUSIONS: In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with lower GFRs might benefit from long-term treatment with tolvaptan, as has been observed for patients with preserved GFRs.

EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1.

BACKGROUND: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (pNETs) are the leading MEN1-related cause of death. OBJECTIVE: To evaluate EUS and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET), compared with the recommended screening techniques in MEN1 patients for early detection of pNETs. DESIGN: Cross-sectional study. SETTING: Tertiary-care university medical center. PATIENTS: This study involved 41 patients with a proven MEN1 mutation or with one MEN1 manifestation and a mutation carrier as a first-degree family member, with recent screening by abdominal CT or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS). INTERVENTIONS: EUS by using a linear Pentax echoendoscope and Hitachi EUB-525 and (11)C-5-HTP PET. MAIN OUTCOME MEASUREMENTS: Patient-based and lesion-based positivity for pNET was calculated for all imaging techniques. The McNemar test was used to compare the yield of the 4 imaging techniques. RESULTS: In 35 of 41 patients, 107 pancreatic lesions were detected in total. EUS detected 101 pancreatic lesions in 34 patients, (11)C-5-HTP PET detected 35 lesions in 19 patients, and CT/MRI + SRS detected 32 lesions in 18 patients (P < .001). (11)C-5-HTP PET performed similarly to CT/MRI + SRS and better compared with SRS only (13 lesions in 12 patients), both at a patient-based and lesion-based level (P < .05). LIMITATIONS: Single-center study. CONCLUSION: EUS is superior to CT/MRI + SRS for pancreatic lesion detection in patients with MEN1. In this setting, (11)C-5-HTP PET is not useful. We recommend EUS as the first-choice pancreas imaging technique in patients with MEN1. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR1668.).

Clinical validation of FDG-PET/CT in the radiation treatment planning for patients with oesophageal cancer.

BACKGROUND: The aim of this prospective study was to determine the proportion of locoregional recurrences (LRRs) that could have been prevented if radiotherapy treatment planning for oesophageal cancer was based on PET/CT instead of CT. MATERIALS AND METHODS: Ninety oesophageal cancer patients, eligible for high dose (neo-adjuvant) (chemo)radiotherapy, were included. All patients underwent a planning FDG-PET/CT-scan. Radiotherapy target volumes (TVs) were delineated on CT and patients were treated according to the CT-based treatment plans. The PET images remained blinded. After treatment, TVs were adjusted based on PET/CT, when appropriate. Follow up included CT-thorax/abdomen every 6months. If LRR was suspected, a PET/CT was conducted and the site of recurrence was compared to the original TVs. If the LRR was located outside the CT-based clinical TV (CTV) and inside the PET/CT-based CTV, we considered this LRR possibly preventable. RESULTS: Based on PET/CT, the gross tumour volume (GTV) was larger in 23% and smaller in 27% of the cases. In 32 patients (36%), >5% of the PET/CT-based GTV would be missed if the treatment planning was based on CT. The median follow up was 29months. LRRs were seen in 10 patients (11%). There were 3 in-field recurrences, 4 regional recurrences outside both CT-based and PET/CT-based CTV and 3 recurrences at the anastomosis without changes in TV by PET/CT; none of these recurrences were considered preventable by PET/CT. CONCLUSION: No LRR was found after CT-based radiotherapy that could have been prevented by PET/CT. The value of PET/CT for radiotherapy seems limited.

The cumulative risk of multiple CT exposures using two different methods.

The aim of this study was to compare the summing method (A) with the complement method (B) for calculating the cumulative lifetime-attributable-risk (LAR(tot)) of tumor incidence and mortality of multiple CT exposures. Method A defines LAR(tot) as the summation of the risk of each separate exposure. Method B was defined as the complement of the probability of inducing no cancer in N separate exposures. The risk of each separate exposure was estimated using dose, gender, and age at exposure (BEIR VII phase 2). Both methods were compared in a simulation and applied to a database of 11,884 patients exposed to multiple CTs. The relative difference between the methods was defined as ΔP%. Simulation confirmed that Method A always overestimates LAR(tot). ΔP% was proportional to the dose per exposure and the number of exposures. The differences between Methods A and B were small. Average LAR(tot) of tumor incidence was 0.140% (Method A) and 0.139% (Method B) with maxima of 5.70% and 5.56%, respectively. Average LAR(tot) of mortality was 0.085% for both methods, with maxima of 2.20% and 2.18%, respectively. ΔP% was highest (2.43%) for a female patient (3-y old) exposed to eight recurrent scans and a cumulative dose of 144 mSv. Although Method B is more accurate, both methods can be used to estimate the cumulative risk of multiple CT exposures. These results have to be interpreted, however, in the perspective of the uncertainties in the cancer risk model, which have been estimated at a factor of 2 or 3.

Evaluation of progression prior to surgery after neoadjuvant chemoradiotherapy with computed tomography in esophageal cancer patients.

BACKGROUND: The risk of tumor progression during neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) is around 8% to 17%. We assessed the efficacy of computed tomography (CT) to identify these patients before esophagectomy. METHODS: Ninety-seven patients with locally advanced EC treated with Carboplatin/Paclitaxel and 41.4 Gy neoadjuvantly were restaged with CT. Two radiologists reviewed pre- and post-CRT CT images. The primary outcome was detection of clinically relevant progressive disease. Missed metastases were defined as metastatic disease found during surgery or within 3 months after post-CRT CT. RESULTS: Progressive disease was detected in 9 patients (9%). Both radiologists detected 5 patients with distant metastases (liver, n = 4; lung metastasis, n = 1), but missed progressive disease in 4 cases. One radiologist falsely assessed 2 metastatic lesions, but after agreement progressive disease was detected with sensitivity and specificity of 56% and 100%, respectively. CONCLUSION: CT is effective in detecting clinically relevant progressive disease in EC patients, after neoadjuvant treatment.

Duct-to-duct reconstruction in liver transplantation for primary sclerosing cholangitis is associated with fewer biliary complications in comparison with hepaticojejunostomy.

There is no consensus on the preferred type of biliary reconstruction for patients undergoing orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC). The aim of this study was to compare long-term outcomes after OLT for PSC using either duct-to-duct anastomosis or Roux-en-Y hepaticojejunostomy for biliary reconstruction. In a consecutive series of 98 adult patients undergoing OLT for PSC, 45 underwent duct-to-duct reconstruction, and 53 underwent Roux-en-Y biliary reconstruction. The median follow-up was 8.2 years (interquartile range = 3.9-14.5 years). The outcomes of the 2 groups were compared. There were no significant differences in patient demographics or general surgical variables between the groups. The overall patient and graft survival rates were similar for the 2 groups. The incidence of biliary strictures and biliary leakage within the first year after transplantation did not differ between the 2 groups. However, significantly more patients in the Roux-en-Y group suffered at least 1 episode of cholangitis within the first year (9% in the duct-to-duct group versus 25% in the Roux-en-Y group, P = 0.04). In addition, Roux-en-Y reconstruction was associated with a significantly higher rate of late-onset (>1 year after transplantation) nonanastomotic biliary strictures (NAS) in comparison with duct-to-duct reconstruction (24% versus 7% at 5 years and 30% versus 7% at 10 years, P = 0.01). In conclusion, duct-to-duct biliary reconstruction in patients with PSC is associated with lower rates of posttransplant cholangitis and late-onset NAS in comparison with Roux-en-Y hepaticojejunostomy. If technically and anatomically feasible, duct-to-duct anastomosis can be performed safely in patients undergoing OLT for PSC.

Influence of preoperative chemotherapy on CT volumetric liver regeneration following right hemihepatectomy.

BACKGROUND: An increasing number of patients undergo major liver resection following preoperative chemotherapy. Liver regeneration may be impaired in these patients, predisposing them to postoperative liver dysfunction. The aim of the present study was to evaluate the effects of preoperative chemotherapy on liver regeneration after partial liver resection. METHODS: Patients planned to receive right hepatectomy either with (group B) or without (group A) prior chemotherapy were identified retrospectively from a prospective multi-institutional database created in the conduct of a national randomized controlled trial (RCT). Prior chemotherapy was neither an inclusion nor an exclusion criterion of the trial. Future remnant liver volume (FRLV) was calculated by measuring total functional liver volume and resection specimen on preoperative computed tomography (CT) scans. Remnant liver volume after 7 days (V RLV7days) was measured on scheduled postoperative CT scans. The early regeneration index 7 days after surgery (RI early) was calculated as [(V RLV7days - FRLV) / FRLV] × 100 %. Data are expressed as median (interquartile range). RESULTS: A total of 72 patients were enrolled: 45 in group A and 27 in group B. For the whole group, the liver remnant showed a 58 % (39 %) increase in volume at day 7 (1) day. The RI early was not significantly different between groups A and B, 60 % (36 %) and 50 % (43 %), respectively (p = 0.47). The RI early was significantly lower in patients who had undergone more than six cycles of chemotherapy. CONCLUSIONS: Preoperative chemotherapy does not seem to have a negative impact on early liver regeneration after partial liver resection.

Computer-assisted solid lung nodule 3D volumetry on CT: influence of scan mode and iterative reconstruction: a CT phantom study.

OBJECTIVE: To evaluate the effect of high-resolution scan mode and iterative reconstruction on lung nodule 3D volumetry. METHODS: Solid nodules with various sizes (5, 8, 10 and 12 mm) were placed inside a chest phantom. CT images were obtained with various tube currents, scan modes (conventional mode, high-resolution mode) and iterative reconstructions [0, 50 and 100 % blending of adaptive statistical iterative reconstruction (ASiR) and filtered back projection]. The nodule volumes were calculated using semiautomatic software and compared with the assumed volume from the nodules. RESULTS: The mean absolute and relative percentage error improved when using iterative reconstruction especially when using the conventional scan mode; however, this effect was not significant. Significant reduction in volume overestimation was observed when using high-resolution scan mode (P = 0.011). CONCLUSION: The high-resolution mode significantly reduces the volume overestimation of 3D volumetry. Iterative reconstruction shows a reduction in volume overestimation and error margin especially with the conventional scan mode; however, this effect was not significant.

The impact of hepatic steatosis on liver regeneration after partial hepatectomy.

BACKGROUND & AIM: Experimental studies in animals have suggested that liver regeneration is impaired in steatotic livers. However, few studies have focused on the impact of steatosis in patients undergoing partial hepatectomy (PH). This study aims to determine the role of steatosis on liver regeneration in humans following PH. METHODS: Eighty-eight patients undergoing PH were included in this study. All patients underwent CT-scanning of the liver preoperatively and 7 days after surgery. Additional CT-scans were performed 6 months post-operatively. Preoperative and post-operative volumes of the total liver (TLV), future liver remnant (FLR) and liver remnant (LR) were measured on CT-scans. Regeneration indices (RI) were calculated at 7 days and 6 months using the formula: (Volume LR-Volume FLR)/Volume FLR × 100%. Based on histological examination of the resected part of the liver, patients were classified into three groups: (1) no steatosis, (2) mild steatosis (1-29%) and (3) moderate-to-severe steatosis (≥30%). RESULTS: The early RI (at day 7) was 40%, 24% and 20% for patients in group 1, 2 and 3 respectively. Late RI (at 6 months) was 81% for group 1, 44% for group 2 and 22% for group 3 (P = 0.019). At 7 days, the LR represented 79%, 80% and 79% of the TLV for groups 1-3. At 6 months, this was 93%, 92% and 79% respectively. CONCLUSION: Although early RI after PH did not differ in patients with or without steatosis, the late RI in patients with moderate-to-severe steatosis was lower, suggesting that late liver regeneration is impaired in these patients.

Fibrin sealant for prevention of resection surface-related complications after liver resection: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of fibrin sealant in reducing resection surface-related complications in liver surgery. BACKGROUND: Bile leakage, bleeding, and abscess formation are major resection surface-related complications after liver resection. It is unclear whether application of fibrin sealant to the resection surface is effective in reducing these complications. METHODS: In a multicenter, randomized trial in 310 noncirrhotic patients undergoing liver resection, we compared prophylactic application of fibrin sealant to the resection surface (156 patients) with no application of fibrin sealant (154 patients). In addition to clinical assessments, patients underwent protocolized computerized tomography (CT) scan 1 week postoperatively. Primary endpoint was a composite of postoperative resection surface-related complications (bile leakage, bleeding, or abscess), as adjudicated by a clinical-events committee that was unaware of the study-group assignments. RESULTS: Overall rate of resection surface-related complications was not different between the 2 groups: 24% (38/156 patients) in the fibrin sealant group and 24% (37/154 patients) in the control group. Bile leakage was detected in 14% of patients in the fibrin sealant group and in 14% of controls. CT scans showed a fluid collection at the resection surface 100 mL or more in 28% of patients in the fibrin sealant group and in 26% of controls (P = 0.800). The rate of reinterventions for resection surface-related complications (12% vs 10%; P = 0.492) and severity of complications did also not differ between the 2 groups. CONCLUSIONS: This randomized multicenter trial shows that prophylactic application of fibrin sealant at the resection surface after liver resections does not lead to a reduction in the incidence or severity of postoperative bile leakage or other resection surface-related complications (Controlled trial number, ISRCTN85205641).

Cost-effectiveness of adding FDG-PET or CT to the diagnostic work-up of patients with stage III melanoma.

OBJECTIVE: The aim of this prospective study was to assess predictive value of fludeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) and to analyze their cost-effectiveness in several diagnosis-treatment combinations. BACKGROUND: The incidence of melanoma continues to rise. A proportion will present or recur with lymph node metastases (American Joint Committee on Cancer/Union for International Cancer Control stage III). To detect distant metastases, CT and/or FDG-PET are available. However, few studies have assessed their value and costs in stage III. METHODS: All consecutive patients with melanoma with palpable, proven lymph node metastases (2003-2008) referred for examination with FDG-PET and CT were prospectively included. Sensitivity, specificity, and accuracy, and positive predictive value (PPV) and negative predictive value (NPV) were calculated. In economic evaluation, the costs of diagnostic work-up with and without FDG-PET and CT were compared. RESULTS: Overall, 253 patients with melanoma were included. FDG-PET showed a higher sensitivity than CT: 86.1% compared with 78.2%. Specificity was higher for CT (93.7%) compared with FDG-PET (93.1%). Overall, FDG-PET showed a higher PPV and NPV. Cost-consequence analysis showed that adding CT (True-Positive upstaging in 61 patients) to diagnostic work-up decreased cost by 5.5%, adding FDG-PET (True-Positive upstaging in 68 patients) increased cost by 7.2%, and adding both (True-Positive upstaging in 78 patients) increased cost by 15.1%. CONCLUSIONS: In this study, FDG-PET had higher sensitivity and predictive value, whereas CT had a higher specificity. Adding one of these diagnostic tools improved the staging of stage III patients with less than 10% cost increase. A proposal for stage-specific use of imaging modalities for clinicians caring for patients with melanoma is presented.

Increase in volume of ablation zones during follow-up is highly suggestive of ablation site recurrence in colorectal liver metastases treated with radiofrequency ablation.

PURPOSE: To test the hypothesis that volume changes of ablation zones (AZs) on successive computed tomography (CT) scans could predict ablation site recurrences (ASRs) in patients with colorectal liver metastases treated by radiofrequency (RF) ablation. MATERIALS AND METHODS: RF ablation was performed in 58 patients with 117 metastases. Metastasis volumes and AZ volumes were measured before RF ablation, 1 week after RF ablation (t1), and every 3 months in the first year after RF ablation (t2-t5). Volumetry was performed semiautomatically on CT scans by drawing freehand regions of interest in the portal venous phase on 2-mm-thickness slices. ASR was defined as contrast enhancement on follow-up imaging or by a hot spot on fludeoxyglucose F 18 positron emission tomography combined with computed tomography (FDG-PET/CT) scanning. Proportional volume change of an AZ was defined as the difference in volume percentages between two successive time points of measurement. Negative values represented a volume decrease, and positive values represented a volume increase. Intraobserver variability and interobserver variability were evaluated by using intraclass correlation coefficients (ICCs). RESULTS: ASRs occurred in 15 patients with 27 AZs. An increase in volume occurred in 26 AZs (96%) with ASRs. AZs without ASR showed no volume increase. Although proportional volume changes at t1-t2 were not predictive for ASR, subsequent volume changes were predictive for ASR. Contrast-enhanced CT-based evaluation detected ASRs in 17 (63%) of 27 AZs, 7 (26%) of 27 AZs were negative, and there was doubt in 3 (11%) of 27 AZs. Intraobserver variability and interobserver variability were good (0.998 [95% confidence interval [CI] 0.996-0.999; P < .001] and 0.993 [95% CI 0.987-0.996; P < .001]). CONCLUSIONS: Volumetry of AZs is useful because a volume increase of an AZ during follow-up is highly suggestive of ASR. Negative volume changes of the AZ from t1-t2 were not correlated with the development of ASRs, but subsequent volume changes were predictive for ASRs.

Lack of Anatomical Concordance between Preablation and Postablation CT Images: A Risk Factor Related to Ablation Site Recurrence.

Objective. Variation in the position of the liver between preablation and postablation CT images hampers assessment of treatment of colorectal liver metastasis (CRLM). The aim of this study was to test the hypothesis that discordant preablation and postablation imaging is associated with more ablation site recurrences (ASRs). Methods. Patients with CRLM were included. Index-tumor size, location, number, RFA approachs and ablative margins were obtained on CT scans. Preablation and postablation CT images were assigned a "Similarity of Positioning Score" (SiPS). A suitable cutoff was determined. Images were classified as identical (SiPS-id) or nonidentical (SiPS-diff). ASR was identified prospectively on follow-up imaging. Results. Forty-seven patients with 97 tumors underwent 64 RFA procedures (39 patients/63 tumors open RFA, 25 patients/34 tumours CT-targeted RFA, 12 patients underwent >1 RFA). Images of 52 (54%) ablation sites were classified as SiPS-id, 45 (46%) as SiPS-diff. Index-tumor size, tumor location and number, concomitant partial hepatectomy, and RFA approach did not influence the SiPS. ASR developed in 11/47 (23%) patients and 20/97 (21%) tumours. ASR occurred less frequently after open RFA than after CT targeted RFA (P < 0.001). ASR was associated with larger index-tumour size (18.9 versus 12.8 mm, P = 0.011). Cox proportional hazard model confirmed SiPS-diff, index-tumour size >20 mm and CT-targeted RFA as independent risk factors for ASR. Conclusion. Variation in anatomical concordance between preablation and postablation images, index-tumor size, and a CT-targeted approach are risk factors for ASR in CRLM.

Copeptin, a surrogate marker of vasopressin, is associated with disease severity in autosomal dominant polycystic kidney disease.

BACKGROUND AND OBJECTIVES: Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma copeptin concentration (a marker of endogenous vasopressin levels) was measured in 102 ADPKD patients (diagnosis based on Ravine criteria) by an immunoassay. Plasma and urinary osmolarity were also measured. To assess disease severity, GFR and effective renal blood flow were measured by continuous infusion of 125I-iothalamate and 131I-hippuran, total renal volume by magnetic resonance imaging, and 24-hour urinary albumin excretion by nephelometry. RESULTS: In these ADPKD patients, copeptin was associated with the various markers of disease severity in ADPKD (positively with total renal volume [R=0.47] and albuminuria [R=0.39] and negatively with GFR [R=-0.58] and effective renal blood flow [R=-0.52], all P<0.001). These associations were independent of age, gender, and use of diuretics. Copeptin was furthermore associated with plasma osmolarity (P<0.001) but not with 24-hour urinary volume, 24-hour urinary osmolarity or fractional urea excretion (P=0.7, 0.9, and 0.3, respectively). CONCLUSIONS: On cross-sectional analysis, copeptin is associated with disease severity in ADPKD patients, supporting the results of experimental studies that suggest that vasopressin antagonists have a renoprotective effect in ADPKD and offering a good prospect for clinical studies with these agents.

The combination of primary sclerosing cholangitis and CCR5-Δ32 in recipients is strongly associated with the development of nonanastomotic biliary strictures after liver transplantation.

BACKGROUND: The role of the immune system in the pathogenesis of nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) is unclear. A loss-of-function mutation in the CC chemokine receptor 5 (CCR5-Δ32) leads to changes in the immune system, including impaired chemotaxis of regulatory T cells. AIM: To investigate the impact of the CCR5-Δ32 mutation on the development of NAS. METHODS: In 384 OLTs, we assessed the CCR5 genotype in donors and recipients and correlated this with the occurrence of NAS. RESULTS: The CCR5-Δ32 allele was found in 65 (16.9%) recipients. The cumulative incidence of NAS at 5 years was 6.5% in wild-type (Wt) recipients vs 17.2% for carriers of the CCR5-Δ32 allele (P<0.01). In recipients with CCR5-Δ32, 50% of all NAS occurred >2 years after OLT, compared with 10% in the Wt group. In multivariate regression analysis, the adjusted risk of developing NAS was four-fold higher in recipients with CCR5-Δ32 (P<0.01). The highest risk of NAS was seen in patients transplanted for primary sclerosing cholangitis (PSC), who also carried CCR5-Δ32 (relative risk 5.4, 95% confidence interval 2.2-12.9; P<0.01). Donor CCR5 genotype had no impact on the occurrence of NAS. CONCLUSIONS: Patients with the CCR5-Δ32 mutation have a four-fold higher risk of developing NAS, compared with Wt recipients. This risk is even higher in patients with CCR5-Δ32 transplanted for PSC. Late development of NAS is significantly more present in patients with CCR5-Δ32. These data suggest that the immune system plays a critical role in the development of NAS after OLT.

Association of urinary biomarkers with disease severity in patients with autosomal dominant polycystic kidney disease: a cross-sectional analysis.

BACKGROUND: Disease monitoring of autosomal dominant polycystic kidney disease (ADPKD) will become more important with potential upcoming therapeutic interventions. Because serum creatinine level is considered of limited use and measurement of effective renal blood flow (ERBF) and total renal volume are time consuming and expensive, there is a need for other biomarkers. We aimed to investigate which urinary markers have increased levels in patients with ADPKD; whether these urinary markers are associated with measured glomerular filtration rate (mGFR), ERBF, and total renal volume; and whether these associations are independent of albuminuria (urine albumin excretion [UAE]). STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 102 patients with ADPKD (Ravine criteria) and 102 age- and sex-matched healthy controls. INDEX TEST: 24-hour urinary excretion of glomerular (immunoglobulin G), proximal tubular (kidney injury molecule 1 [KIM-1], N-acetyl-ß-d-glucosaminidase, neutrophil gelatinase-associated lipocalin [NGAL], and ß(2)-microglobulin), and distal tubular (heart-type fatty acid binding protein [H-FABP]) damage markers and inflammatory markers (monocyte chemotactic protein 1 [MCP-1] and macrophage migration inhibitory factor). REFERENCE TEST: Disease severity assessed using measures of kidney function (mGFR and ERBF, measured using clearance of iothalamate labeled with iodine 125 and hippuran labeled with iodine 131 during continuous infusion, respectively) and structure (total renal volume, measured using magnetic resonance imaging). OTHER MEASUREMENTS: 24-hour UAE. RESULTS: In 102 patients with ADPKD (aged 40 ± 11 years; 58% men), levels of all measured urinary biomarkers were increased compared with healthy controls. Excretion of immunoglobulin G and albumin relatively were most increased. ERBF and mGFR values were associated with urinary excretion of ß(2)-microglobulin, NGAL, and H-FABP independent of UAE, whereas total renal volume was associated with KIM-1, NGAL, and MCP-1 independent of UAE. LIMITATIONS: Cross-sectional, single center. CONCLUSIONS: Levels of markers for multiple parts of the nephron are increased in patients with ADPKD. In addition to measurement of UAE, measurement of urinary ß(2)-microglobulin, KIM-1, H-FABP, MCP-1, and especially NGAL could be of value for determination of disease severity in patients with ADPKD.

Early renal abnormalities in autosomal dominant polycystic kidney disease.

BACKGROUND AND OBJECTIVES: Potential therapeutic interventions are being developed for autosomal dominant polycystic kidney disease (ADPKD). A pivotal question will be when to initiate such treatment, and monitoring disease progression will thus become more important. Therefore, the prevalence of renal abnormalities in ADPKD at different ages was evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Included were 103 prevalent ADPKD patients (Ravine criteria). Measured were mean arterial pressure (MAP), total renal volume (TRV), GFR, effective renal plasma flow (ERPF), renal vascular resistance (RVR), and filtration fraction (FF). Twenty-four-hour urine was collected. ADPKD patients were compared with age- and gender-matched healthy controls. RESULTS: Patients and controls were subdivided into quartiles of age (median ages 28, 37, 42, and 52 years). Patients in the first quartile of age had almost the same GFR when compared with controls, but already a markedly decreased ERPF and an increased FF (GFR 117 +/- 32 versus 129 +/- 17 ml/min, ERPF 374 +/- 119 versus 527 +/- 83 ml/min, FF 32% +/- 4% versus 25% +/- 2%, and RVR 12 (10 to 16) versus 8 (7 to 8) dynes/cm(2), respectively). Young adult ADPKD patients also had higher 24-hour urinary volumes, lower 24-hour urinary osmolarity, and higher urinary albumin excretion (UAE) than healthy controls, although TRV in these young adult patients was modestly enlarged (median 1.0 L). CONCLUSIONS: Already at young adult age, ADPKD patients have marked renal abnormalities, including a decreased ERPF and increased FF and UAE, despite modestly enlarged TRV and near-normal GFR. ERPF, FF, and UAE may thus be better markers for disease severity than GFR.

Diffusion weighted imaging in the liver.

Diffusion weighted magnetic resonance imaging (DWI) is an imaging technique which provides tissue contrast by the measurement of diffusion properties of water molecules within tissues. Diffusion is expressed in an apparent diffusion coefficient (ADC), which reflects the diffusion properties unique to each type of tissue. DWI has been originally used in neuroradiology. More recently, DWI has increasingly been used in addition to conventional unenhanced and enhanced magnetic resonance imaging (MRI) in other parts of the body. The reason for this delay was a number of technical problems inherent to the technique, making DWI very sensitive to artifacts, which had to be overcome. With assessment of ADC values, DWI proved to be helpful in characterization of focal liver lesions. However, DWI should always be used in conjunction to conventional MRI since there is considerable overlap between ADC values of benign and malignant lesions. DWI is useful in the detection of hepatocellular carcinoma in the cirrhotic liver and detection of liver metastases in oncological patients. In addition, DWI is a promising tool in the prediction of tumor responsiveness to chemotherapy and the follow-up of oncological patients after treatment, as DWI may be capable of detecting recurrent disease earlier than conventional imaging. This review focuses on the most common applications of DWI in the liver.