Retroperitoneal fibrosis Department of nephrology R2 우용식 Lancet Jan 21;367(9506):

Introduction  retroperitoneal tissue of chronic inflammation, marked fibrosis.  can entraps ureters or other abdominal organs  1st description French urologist Albarran, 1905 : surgical treatment of extensive fibrotic retroperitoneal process causing ureteral obstruction  Ormond, 1948 : published his account of two cases in English

Schematic representation of idiopathic retroperitoneal fibrosis, inflammatory abdominal aneurysm, perianeurysmal retroperitoneal fibrosis

Epidemiology and diagnosis  incidence - 0.1/ person-yrs prevalence / inhabitants  Men, twice ~ three times as often as women mean age at presentation 50–60 yrs  children, older adults are not uncommon  no evidence of familial clustering in cases, reported in twins and siblings

Epidemiology and diagnosis  no standard diagnostic criteria  CT or MRI scans : choice for diagnosis, follow-up  suggests a diagnosis of retroperitonealfibrosis : finding of soft-tissue mass, surrounding abdominal aorta, iliac arteries and with possible encasement of neighbouring structures such as ureters and IVC  raised concentrations of acute phase reactants (ESR,CRP et al)

Epidemiology and diagnosis  histological examination of retroperitoneal tissue : needed when atypical localisations (pelvic, peripancreatic) presence of underlying malignant disease or infections

Pathogenesis (Idiopathic retroperitoneal fibrosis) Two potential pathogenetic mechanisms of chronic periaortitis

Pathogenesis (Idiopathic retroperitoneal fibrosis)  antigens (LDL,ceroid) laden macrophages →B,T lymphocytes activated in medial, adventitial layers → inflammatory extends into periaortic retroperitoneum  chronic periaortitis,initiated in adventitia → vasa vasorum vasculitis → weakening of aortic wall → extend into retroperitoneum

Pathogenesis (Idiopathic retroperitoneal fibrosis)  mediated by antibodies against fibroblasts  presence of IgG4-bearing plasma cells  environmental factors (exposure to asbestos)

Pathogenesis (secondary retroperitoneal fibrosis)  Carcinoids may induce without metastasising to retroperitoneum  : probably through serotonin-mediated mechanism or by release of profibrogenic growth factors

Clinical manifestations

 Ureteral involvement, reported in 80~100%  involvement is often bilateral  pt with unilateral obstruction, contralateral can develop even within a short period.  with non-functioning kidneys, probably caused by long-lasting hydronephrosis

Laboratory findings  routine lab. consistent with inflammatory dz  Con. of acute-phase reactants (ESR,CRP) high in 80–100% of pts often used to monitor clinical course of disease  Azotemia depends on extent of ureteral obstruction  Mild-to-moderate anemia both chronic inflammation and present—renal insufficiency  Leucocytosis, eosinophilia, proteinuria, microscopic haematuria less common

 tests for autoimmune disease ANA(+) - most frequent, detected in 60% of pts RF, anti-sm, anti-dsDNA, ENA → titres ; low, non-specific but can suggest presence of connective tissue disease  ab against thyroid microsome & thyroglobulin usually indicates autoimmune thyroiditis

Imaging  Sonography as a first-line study, of azotemic patient appears as a hypoechoic or isoechoic mass involve the ureters, cause unilateral or bilateral hydronephrosis  Intravenous urography triad : medial deviation, extrinsic comp. of ureters, hydronephrosis can be caused by ureteral tumours, inflammatory processes, and adenopathy

Imaging  CT and MRI : most reliable imaging modalities  unenhanced CT homogeneous plaque, isodense with muscle, surrounding the lower abdominal aorta and the iliac a. often enveloping the ureters and inferior vena cava  most retroperitoneal fibrosis secondary to malignancy tend to displace aorta anteriorly, ureters laterally  Contrast medium improves visibility in only early stages

Imaging  MRI - avoidance of nephrotoxic contrast provides better definition hypointense in T1-weighted images in T2-weighted images high in the early or active stages low in the late stages malignant retroperitoneal fibrosis : inhomogeneous signal on T2-weighted images

Imaging  Fluorodeoxyglucose-positron emission tomography (FDG-PET) not useful for the diagnosis of retroperitoneal fibrosis d/t low specificity assessing the metabolic activity of retroperitoneal mass reveal other disease detect occult neoplastic or infectious to secondary can assess full extent of vascular involvement

medial deviation and Extrinsiccompression (arrows) of ureters andhydroureteronephrosis.

soft tissue mass, surrounding abdominal aorta (arrows, right panel) common iliac arteries (arrows, left panel) with associated left ureterohydronephrosis (arrowheads, left panel)

Scans show pronounced uptake of 18F fluorodeoxyglucose in thoracic and abdominal aorta (arrows; left panel=tridimensional view, central panel=sagittalview, right panel=coronal view).

Associated autoimmune diseases

Differential diagnoses  Retroperitoneal fibromatosis characterised by a uniform proliferation of fibroblasts Originates from connective tissue of m. & fascia infiltrative growth, often recurs after excision, but not metastasise ass. with Gardner’s syndrome, a variant of familial adenomatous polyposis  Inflammatory myofibroblastic tumour mainly affects children characterized by myofibroblast proliferation,ass. with myxoid & inflammatory areas. local recurrence, but rare distant meta.

Differential diagnoses  Inflammatory malignant fibrous histiocytoma inflammatory fibrosarcoma show increased cellularity,vascularity, nuclear atypism, mitoses.

Treatment and course  aims of treatment of idiopathic retroperitoneal fibrosis to stop progression of fibroinflammatory reaction, to inhibit or relieve obstruction of ureters or other retroperitoneal structures, to switch off acute-phase reaction, systemic manifestations to prevent disease recurrence or relapse.

 Corticosteroids initial daily dose of prednisone 40–60 mg to prevent relapses, treatment of up to 2 yrs.  some resistant to steroids.  optimum dose, duration of therapy not well established  most published studies only small case series and are retrospective and uncontrolled.

 Immunosuppressants (cyclophosphamide,azathioprine,methotrexate, cyclosporin, mycophenolate mofetil, tamoxifen) used as second-line therapy in steroid-refractory patients  Surgery done to relieve ureteral obstruction (open ureterolysis with intraperitoneal transposition, omental wrapping of the ureters)  not prevent disease progression and recurrence  no effect on systemic manifestations

 Monitoring after the initiation of therapy by subjective symptoms and regular assessment of ESR and CRP concentrations. sono. : useful in follow-up of ureteral obstruction. CT and MRI :reliable in assessment of changes in size of retroperitoneal tissue

 outlook for pts : usually be good severe complications can arise.  predictors of response to therapy, corticosteroid requirement, or disease relapse : no identified.  relapse rate after therapy : difficult to establish  ureteral obstruction estimated to recur up to half of pts surgery alone about 10% treated with steroids