Clinical significance of soluble interleukin-2 receptor measurement in patients with idiopathic retroperitoneal fibrosis.

BACKGROUND: Idiopathic retroperitoneal fibrosis (iRPF) is a rare chronic fibro-inflammatory disorder of unknown etiology. Activated T-helper cells, which shed soluble interleukin-2 receptor (sIL-2R) into the circulation, may play a pathogenetic role. Hence, measuring sIL-2R may be of value in monitoring disease activity and treatment response in iRPF patients. METHODS: We performed a prospective inception cohort study of 82 patients with untreated (re)active iRPF stratified by elevated (> 623 U/mL) or normal sIL-2R level at baseline and compared disease characteristics among these groups. Baseline and changes in sIL-2R levels following treatment with tamoxifen (TMX) or prednisone (PDN) were analyzed and related to treatment response. RESULTS: Median sIL-2R level was 668 U/mL (IQR 502.8-827.5); 48 patients (59%) had elevated baseline sIL-2R levels. Patients with elevated sIL-2R presented with higher CRP (P = 0.049) and serum creatinine (sCr) levels (P < 0.001) and more often had hydroureteronephrosis (P = 0.01). There was an age and sex adjusted linear association between baseline sIL-2R and both CRP (P = 0.02) and sCr (P < 0.001). Baseline and serial levels of sIL-2R were predictive and concordant, respectively, with clinical response in patients treated with PDN. ROC curve analyses of sIL-2R on a continuous scale and PDN treatment success showed an AUC of 0.84. A serum sIL-2R cut-off value for PDN treatment success of ≤ 703 U/mL was found with a sensitivity of 100% and specificity of 72%. CONCLUSION: Serial measurement of sIL-2R may be of value in monitoring disease activity and PDN treatment response in iRPF patients.

Abdominal aortic diameter and cardiovascular status in patients with idiopathic retroperitoneal fibrosis.

Although much debated, an exaggerated inflammatory response to advanced atherosclerosis has been implicated in the pathogenesis of idiopathic retroperitoneal fibrosis (RPF). Clinical presentation, infrarenal abdominal aortic diameter and RPF mass thickness were retrospectively analyzed in 166 patients with idiopathic RPF seen at our referral center between April 1998 and December 2019. Patients were stratified to their infrarenal abdominal aortic diameter at presentation (i.e., non-ectatic [< 25 mm]; ectatic [25-29 mm]; and aneurysmal [≥ 30 mm]) to compare characteristics across groups with an undilated or dilated aorta. Ectatic or aneurysmal aortic dilatation was present in 34% of patients. Most clinical characteristics did not differ across abdominal aortic diameter stratified groups, but RPF mass thickness was greater in patients presenting with aortic aneurysmal dilatation compared to that in patients with an undilated aorta (49.0 mm [IQR 34.0-62.0] vs 32.5 mm [IQR 25.3-47.8]; P < 0.001). A positive linear association was found between aortic diameter on a continuous scale and RPF mass thickness (ß 0.32 [95% CI 0.34-0.96]; P < 0.001). This association remained significant after adjusting for age, sex and acute-phase reactant levels (ß 0.28 [95% CI 0.15-0.95]; P < 0.01). Treatment success across aortic diameter stratified groups did not differ (P = 0.98). Treatment induced RPF mass regression was not associated with an increase in aortic expansion rate (P = 0.44). Aortic dilatation was prevalent among patients. Infrarenal abdominal aortic diameter was independently associated with RPF mass thickness. Findings support the concept that at least in a subset of patients, RPF may be secondary to advanced atherosclerosis.

Elevated serum IgG4 levels in diagnosis and treatment response in patients with idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (iRPF) may be a manifestation of IgG4-related disease. Measuring serum IgG4 (sIgG4) may be of value in monitoring iRPF, but this has scarcely been evaluated. It is unknown if tamoxifen (TMX) affects sIgG4 levels. We performed a prospective inception cohort study of 59 patients with untreated (re)active iRPF stratified by elevated (>1.4 g/L) or normal sIgG4 level. Changes in sIgG4 levels following TMX initiation and, if treatment failed, during subsequent corticosteroid (CS) treatment were analyzed. The median sIgG4 level was 1.1 g/L (interquartile range (IQR) 0.4-2.2); 24 patients (40%) had elevated sIgG4 level. Patients with elevated sIgG4 tended to present with higher ESR (46 vs. 34 mm/h; P = 0.08) and more frequent locoregional lymphadenopathy adjacent to the mass (41.7 vs. 20.0%; P = 0.08). sIgG4 also correlated with ESR (ρ = 0.26; P = 0.05) and serum creatinine (SC) (ρ = 0.26; P = 0.04). Following TMX initiation, sIgG4 level decreased, particularly when achieving treatment success (P < 0.01). Odds ratio for TMX treatment success in patients with elevated sIgG4 level was 0.77 (95% CI 0.53-1.14; P = 0.19). After adjusting for age, sex, and SC, the odds ratio was 0.78 (95% CI 0.51-1.18; P = 0.24). ROC curve analyses of sIgG4 on a continuous scale and treatment success showed an AUC of 0.62. Treatment success and concurrent sIgG4 decrease (P < 0.01) were achieved in 78% of patients who converted to CS therapy. Patients with elevated sIgG4 level may be more inflammatory than patients with normal sIgG4 level, but this needs further study. TMX affects sIgG4 levels, but to a lesser extent than CSs. sIgG4 cannot be used as an outcome prediction tool, irrespective of which cutoff value was chosen.

Mesenteric panniculitis: prevalence, clinicoradiological presentation and 5-year follow-up.

OBJECTIVE: To determine prevalence, clinicoradiological characteristics and outcome of patients with mesenteric panniculitis (MP) in a large hospital-based population. METHODS: Consecutive abdominal CT examinations of 3820 patients were evaluated for MP. Clinical characteristics, therapy and outcome of patients with MP were evaluated during a 5-year follow-up period. A matched pair analysis was performed to further investigate the relation between MP and malignancy. RESULTS: 94 (2.5%) patients with MP were identified (mean age, 66.6 ± 11.2 years, 70.2% male). MP coexisted with malignancy (especially prostatic carcinoma) in 48.9% of patients, and this was slightly but significantly higher than in age- and sex-matched control patients (n = 188, 46.3%). In 48 patients, MP was presumed to be idiopathic. The most frequent presenting symptom was pain (54.3%). Laboratory findings revealed increased acute-phase reactants in half of the patients with MP. CT findings included increased density of mesenterial fat (mean, -56.8 ± 10.8 HU), fat ring sign, tumoural pseudocapsule and small soft-tissue nodules. Patients with MP (14.6%) developed significantly more malignancies during a 5-year follow-up than did the control group (6.9%). One patient was treated with prednisone without satisfactory response. CONCLUSION: The prevalence of MP in this study was 2.5%. In most patients, radiologic features included increased mesenteric fat density, fat ring sign and small soft-tissue nodules. MP was associated with a significant higher prevalence of coexisting malignancies and a higher prevalence of future cancer development. ADVANCES IN KNOWLEDGE: A more accurate prevalence of MP on CT is demonstrated. An underlying malignancy may play a role.

Long-term safety and efficacy of a tamoxifen-based treatment strategy for idiopathic retroperitoneal fibrosis.

BACKGROUND: Tamoxifen may be a viable treatment option for idiopathic retroperitoneal fibrosis (iRPF) but data are limited and its long-term safety and efficacy is unclear. We describe the long-term course and outcomes in a large group of patients with iRPF treated with tamoxifen monotherapy. METHODS: This is a single-center prospective, observational study of 55 patients with iRPF treated with tamoxifen for 2years from April 1998 through April 2011. Measurements included clinical improvement, laboratory parameters and follow-up computed tomographic (CT) scanning. Treatment success was the composite endpoint of clinical improvement, mass regression and definite resolution of ureteral obstruction. RESULTS: Forty-seven (85%) patients reported substantial resolution of symptoms after median treatment duration of 3.0weeks (IQR 1.4-4.8weeks). Repeated CT scanning showed mass regression in 39 (71%) patients at 4months and 47 (85%) patients at 8months of follow-up, respectively. Nineteen (34.5%) patients did not meet the composite endpoint of treatment success, 56% of whom responded satisfactorily to second-line immunosuppressive treatment. Recurrence-free survival in patients with treatment success after post-treatment follow-up of 21months (IQR 9.0-35.0months) was 68%. Tamoxifen was well tolerated. Pulmonary embolism occurred in 2 patients receiving tamoxifen and in one patient receiving second-line treatment. CONCLUSION: Tamoxifen is a safe and viable therapeutic option in the treatment of iRPF.

Pseudocyst formation in retroperitoneal fibrosis relapse.

We describe a 45-year-old male patient with recurrent retroperitoneal fibrosis (RPF), in whom a pseudocyst in the peri-aortic fibrotic mantle was diagnosed. Without any intervention other than oral treatment with tamoxifen, the pseudocyst showed significant regression. Although rare, pseudocyst formation may sometimes appear in RPF and may mimic other benign and malignant conditions. This is the first paper to describe pseudocyst formation in an RPF relapse.

(18)F-fluorodeoxyglucose position emission tomography (FDG-PET) for monitoring disease activity and treatment response in idiopathic retroperitoneal fibrosis.

OBJECTIVE: To evaluate the value of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in monitoring disease activity and predicting treatment response in idiopathic retroperitoneal fibrosis (iRPF). PATIENTS AND METHODS: This prospective study was approved by the institutional review board. Informed consent was obtained from all patients. Twenty-six patients with iRPF receiving tamoxifen monotherapy underwent repeated FDG-PET (baseline and, if positive, at 3 months) and computed tomographic (CT) scanning (baseline, 4 and 8 months). Maximal RPF mass thickness in 3 different view directions was measured on each CT scan; FDG-uptake was semi-quantified using a visual 4-point scale. Initial and follow-up PET scan results were correlated with clinical, laboratory and CT scan follow-up data. Treatment outcome was the aggregate measure of clinical, laboratory and CT-documented response to tamoxifen. RESULTS: FDG-PET was positive in 20 patients. Patients with positive PET scan result had higher C-reactive protein level (P=0.02) and larger mass size (P=0.01) compared with patients with negative PET scan result. Visual PET score correlated with C-reactive protein level (P=0.002) and CT-documented mass thickness (P=0.04). Visual PET score decreased following treatment (P<0.01). This decrease correlated with decrease in ESR (P<0.001) but not with CT-documented mass regression. Positive predicting value (PPV) of initial positive PET scan result was 0.63; PPV of negative follow-up PET scan result in patients with initial positive PET scan result was 0.66. CONCLUSION: FDG-PET is valuable in detecting (recurrent) disease activity. Short-term follow-up with FDG-PET cannot be routinely recommended for the therapeutic evaluation of RPF disease in tamoxifen-treated patients.

Idiopathic retroperitoneal fibrosis: prospective evaluation of incidence and clinicoradiologic presentation.

Retroperitoneal fibrosis (RPF) is a rare disorder of unknown etiology. Its incidence is unknown, and the insidious and nonspecific nature of symptoms may contribute to considerable diagnostic delay. We conducted the current study to assess the incidence and clinicoradiologic characteristics of idiopathic RPF. For this, we evaluated prospectively 53 consecutive patients with a diagnosis of idiopathic RPF at our tertiary care referral center from April 1998 through January 2008.Calculated annual incidence of RPF was 1.3/100,000 inhabitants. Mean age was 64 +/- 11.1 (SD) yr; male-female ratio was 3.3:1.0. Median duration of symptoms was 6.0 mo (IQR 3.0-12.0). Abdominal, flank, and/or back pain and discomfort were the major symptoms, with visual analogue scale scores of 49 +/- 27.2 mm and 43 +/- 29.4 mm for pain and discomfort, respectively. Female patients had higher erythrocyte sedimentation rate (ESR), higher white blood cell count, and lower hemoglobin content than male patients at presentation. Computed tomography-documented maximal mass thickness amounted to 35 +/- 16.6 mm; craniocaudal length amounted to 137 +/- 48.8 mm. RPF mass extension up to or above the level of the renal vessels was noted in 3 patients (6%). Six patients (11%) presented with atypical RPF localization and/or bulky mass. Localized lymphadenopathy adjacent to the RPF mass was observed frequently (25%). Patients with hydronephrosis (56%) presented earlier than patients without hydronephrosis, with higher creatinine and greater mass thickness but similar pain severity. Patients were typically at high cardiovascular risk with increased-often aneurysmal-infrarenal aortic diameter (25.0 mm, IQR 22.0-30.0). RPF mass distribution was similar in patients with or without aneurysmal dilation. Occupational asbestos exposure (20%) and asbestos-related pleural changes (17%) were frequent among males. Previous or concurrent chronic inflammatory disease and/or autoimmune disease was noted in 8 patients (15%). Multivariate analysis revealed an independent association of ESR values with severity of pain and discomfort. Smoking was independently associated with infrarenal aortic diameter.In summary, annual RPF incidence is higher than previously assumed. Age at diagnosis and male-female ratio seem to have changed over time. RPF typically affects patients at high cardiovascular risk, including increased aortic diameter. Clinical presentation is influenced by sex, severity of inflammation and presence of hydronephrosis. Prolonged asbestos exposure and asbestos-related pleural changes were frequent among males. Localized lymphadenopathy adjacent to the RPF mass occurs frequently and should not confuse RPF diagnosis.

Persistent chronic peri-aortitis ('inflammatory aneurysm') after abdominal aortic aneurysm repair: systematic review of the literature.

Data on the outcome of aneurysmal chronic peri-aortitis ('inflammatory aneurysm') after open surgical aneurysm repair are few and contradictory. To what extent this inflammatory process is reversed after endovascular aneurysm repair (EVAR) is even more unclear. The objective of this review was to study the outcome of peri-aortic fibrosis (PAF) and ureteral obstruction in patients with aneurysmal chronic peri-aortitis treated with open surgery or EVAR. Medical literature was searched for pertinent articles on the outcome of PAF and ureteral obstruction after open surgery or EVAR from 1970 through October 2007. Studies were included if specific follow-up data were available on outcomes of interest. A total of 19 studies were included comprising 478 patients (open surgical, n = 426; EVAR, n = 52). Age, sex and percentage of patients with ureteral obstruction (31% vs 37%) did not differ between groups. Regression of PAF occurred more frequently after open surgery compared to EVAR (86% vs 60%; p < 0.0001). Complete regression of PAF was more frequent after open surgery compared to EVAR (52% vs 14%; p < 0.0001). After excluding patients in whom concurrent ureterolysis was performed, the frequency of persistent ureteral obstruction remained lower in patients treated surgically compared to patients treated with EVAR, albeit not statistically significant (32% vs 56%; p = 0.09). In conclusion, although open surgery is superior to EVAR in achieving regression of chronic peri-aortitis, the frequency of persistent PAF and/or ureteral obstruction is not negligible. Additional medical and/or urological treatment should be considered in selected cases of aneurysmal chronic peri-aortitis.

Clinical value of gallium-67 SPECT scintigraphy in the diagnostic and therapeutic evaluation of retroperitoneal fibrosis: a prospective study.

BACKGROUND: Gallium-67 (67Ga) scintigraphy may be useful in evaluating patients with retroperitoneal fibrosis (RPF), but a systematic assessment of its value is lacking. OBJECTIVE: Prospective evaluation of the value of 67Ga scintigraphy in assessing active RPF disease and in predicting treatment response. METHODS: Thirty-four patients with nonmalignant RPF treated with tamoxifen underwent 67Ga scintigraphy at baseline and--if baseline gallium scan was positive--at 3 months follow-up. Gallium scans were visually scored according to pathologic 67Ga-uptake compared to normal bone marrow 67Ga-uptake. Results were correlated with other (follow-up) measurements. Value of (follow-up) 67Ga scintigraphy in predicting treatment response was also assessed. RESULTS: Gallium scans were positive in 24 patients (71%). Mass thickness was greater in patients with positive gallium scan compared with patients with negative gallium scan (P = 0.006). Visual gallium score correlated with mass thickness (P = 0.006). Visual gallium score decreased significantly following tamoxifen treatment (P < 0.0001). Decrease in visual gallium score correlated with decreases in C-reactive protein and erythrocyte sedimentation rate (P = 0.019) and with decrease in mass thickness (P < 0.01). Positive predicting value (PPV) of positive baseline gallium scan was 0.71; PPV of negative follow-up gallium scan in patients with initial positive scan was 0.89. 67Ga scintigraphy detected extra-abdominal involvement in one patient and recurrent active disease in two symptomatic patients with normal acute-phase reactants and stable residual mass. CONCLUSION: 67Ga scintigraphy is useful in assessing (recurrent) activity of RPF disease and in evaluating treatment response in patients with initial positive gallium scan.

[Diagnostic image (300). A man with progressive bilateral leg oedema]. / Diagnose in beeld (300). Een man met progressiefoedeem aan beide benen.

In a 76-year-old man bilateral leg oedema was caused by compression of the V. cava inferior by a large abdominal aortic aneurysm. The oedema resolved after an aortobiiliac prosthesis was placed.