Friday, October 31, 2014

Retroperitoneal Fibrosis (RPF): Insidious Obstructor of the Ureters

Retroperitoneal fibrosis (RPF) is a benign condition in which the proliferation of fibrotic and inflammatory tissue obstructs retroperitoneal structures including one or both ureters. While RPF is most often managed by nephrologists, it represents a benign proliferation of tissue that may require evaluation and management by urology.  This blog will review the basics of RPF.

Epidemiology and Etiology

In large, cross-sectional studies RPF is a rare disease, presenting in only 0.1 to 1 per 100,000 to 200,000 people.[1, 2] It is more common in men than women (ratio 2-3:1) and typically presents later in life - in the 6th-7th decade - although has been found in both the pediatric and elderly populations.[3, 4] While an inheritance pattern has not been documented, RPF is linked to a number of autoimmune disorders and the HLA-DRB1*03 allele which is linked to multiple sclerosis and rheumatoid arthritis.[5]

The etiology of RPF is not well understood and a number of theories exist. Possible causes include a vasculitis (inflammation) of the small vessels associated with the aorta,[6] immunologic dysregulation that produces an antibody reaction to fibroblasts or a B-cell disorder,[7, 8] or reactive inflammation in response to environmental toxins. As such, a number of medications, chemicals, radiation treatment, local and systemic diseases are associated with the development of RPF (Table).[7, 9] However, a specific etiology is identified in only 30% of RPF cases.[10] Malignancy is associated with 8-10% of RPF cases and should always be considered during initial work-up.[11]  Breast and prostate cancers are historically the cancers that can create a retroperitoneal mass similar to RPF.

Autoimmune Disorders

Medications (cont.)
Ankylosing Spondylitis
Primary Biliary Cirrhosis
Rheumatoid Arthritis
Sclerosing Cholangitis
Retroperitoneal Disease, Trauma or Surgery
Thyroid Disease
Aortic or iliac artery aneurysm; repair thereof
Ascending lymphangitis
Vasculitis, small- or medium-sized vessels
Collagen vascular disease
Henoch-Schonlein purpura with hemorrhage
Methyl methacrylate
Inflammatory response to advanced atherosclerosis
Talcum powder
Ruptured viscera
Retroperitoneal Malignancy
Chronic urinary tract infection
Renal Cell Carcinoma
Urothelial Carcinoma
Any radiation or chemotherapy thereof
β Blockers
Systemic Disease
Inflammatory Bowel Disease
Ergotamine alkaloids

Erdheim-Chester disease


RPF is an insidious, slowly developing disease.  Because it develops so slowsly, symptoms are often imperceivable.  Therefore, patients are often asymptomatic or present in an advanced stage when symptoms of ureteral or vascular obstruction occur.[11] Non-specific signs and symptoms may be related to the underlying etiology. Back, abdominal or flank pain have been described, as have constitutional symptoms (weight loss, anorexia, malaise), low-grade fever, hypertension or lower extremity edema related to chronic vascular obstruction. Blood tests may reveal changes in acute phase reactants (erythrocyte sedimentation rate, c-reactive protein) are elevated in 80-100% of patients and serum creatinine, hypergammaglobulinemia, anemia and autoimmune factors (antinuclear antibody, rheumatoid factor, etc.) may be abnormal but, in general, are not specific for RPF.[7, 12]

Typical findings on imaging include hydronephrosis (swelling of the renal pelvis and ureter), medial deviation of the ureter(s) and a smooth, well-demarcated retroperitoneal mass that surrounds the aorta, inferior vena cava (IVC), iliac vessels and ureters. CT and MRI are excellent modalities for establishing a diagnosis although ultrasound and intravenous pyelography can be used as adjuncts.[11, 13, 14] The retroperitoneal mass may involve one or both sides of the retroperitoneum. If unilateral, the mass may progress to cross the midline and involve bilateral structures (i.e. ureters) over time.

Histology and Pathology

RPF appears as a fibrous, white plaque that encases the major retroperitoneal vessels and structures. Most commonly it involves the aorta, inferior vena cava, major branches of both great vessels and the ureters. The plaque usually extends cranially from the renal hilum to the pelvic brim caudally, although has been demonstrated to extend into the pelvis or mediastinum. Histologically the plaque is composed of fibrotic cellular material (myofibroblasts, type-1 collagen) and a chronic inflammatory infiltrate (lymphocytes, macrophages, plasma cells and eosinophils).[8]


Biopsy is required for the diagnosis of RPF and to exclude malignancy. Core biopsy is preferred to fine needle aspiration; open or laparoscopic biopsy can be performed during ureterolysis if indicated. If histologic findings are consistent with RPF, the first step is to stop all potentially inciting agents or exposures (Table). However, if obstructive uropathy is present, primary therapy should be directed at relieving the obstruction and maintaining renal function prior to initiating a biopsy for diagnosis or medical treatment. Retrograde ureteral stents are often easily passed in patients with RPF, however stents can paradoxically obstruct narrowed ureters associated with RPF. Alternatively, percutaneous nephrostomy tubes offer a reliable drainage method if stenting is not possible or unsuccessful.

Dr. Paul Scheel, MD
Once the urinary obstruction is relieved and a tissue diagnosis is obtained, medical therapy is the preferred initial treatment. Primary treatment is directed at assumed autoimmune and inflammatory etiologies of RPF, initially with a prolonged course of corticosteroids. Using prednisolone or prednisone, a number of dosing regimens are demonstrated to be initially effective in 67-89% of patients with follow-up extending from 15-55 months.[15-17] Azathioprine, colchicines, cyclophosphamide, mycophenolate mofetil and tamoxifen have been used to treat patients with severe RPF or RPF refractory to steroids.[16, 18-21] Importantly, no randomized, prospective studies exist addressing the utility of varying medical treatments or the initial use of medical versus surgical treatment for RPF. Dr. Paul Scheel, MD and Director of the Division of Nephrology at the Johns Hopkins Hospital, is a world expert and leader in the management of RPF. You can visit Dr. Scheel's website by clicking here or on the link below.

In patients refractory or unable to undergo medical treatment, ureterolysis can be performed to relieve ureteral obstruction. Ureterolysis involves completely freeing the ureters from the retroperitoneal mass. It can be performed via an open, laparoscopic or robot-assisted laparoscopic approach.[22, 23]  See the video below for robot-assisted laparoscopic ureterolysis.  Principles of ureterolysis include: biopsy of the fibrotic lesion, initiation of dissection in an area free of disease, avoidance of devascularization of the ureter, lateralization of the ureter, stenting for 6-8 weeks and enclosure within peritoneum or omentum to preserve ureteral vascularity and prevent recurrence.[24] In addition, bilateral ureterolysis should be performed in all cases (even if only a unilateral process is evident during evaluation) as disease can progress to involve both sides and reoperative surgery can be technically challenging. Successful treatment has been reported in 66-100% of surgical series with variable follow-up extending over many years.[22, 25, 26] However, ureterolysis is a complicated, challenging, rare surgery and should only be performed as a last resort. Therefore long-term follow-up is required with serial axial imaging and renal functional studies for an indefinite period of time.

Link: Retroperitoneal Fibrosis at Johns Hopkins Medicine.

This blog is adapted from the Handbook of Urology, Chapter 24: Angiomyolipoma, Oncocytoma and Retroperitoneal Fibrosis, by Phillip M. Pierorazio, MD; Edited by John Kellogg Parsons, John B. Eifler, and Misop Han available from Wiley.


1.    Uibu, T., et al., Asbestos exposure as a risk factor for retroperitoneal fibrosis. Lancet, 2004. 363(9419): p. 1422-6.
2.    Debruyne, F.M., M.J. Bogman, and A.F. Ypma, Retroperitoneal fibrosis in the scrotum. Eur Urol, 1982. 8(1): p. 45-8.
3.    Wu, J., E. Catalano, and D. Coppola, Retroperitoneal fibrosis (Ormond's disease): clinical pathologic study of eight cases. Cancer Control, 2002. 9(5): p. 432-7.
4.    Miller, O.F., et al., Presentation of idiopathic retroperitoneal fibrosis in the pediatric population. J Pediatr Surg, 2003. 38(11): p. 1685-8.
5.    Martorana, D., et al., Chronic periaortitis and HLA-DRB1*03: another clue to an autoimmune origin. Arthritis Rheum, 2006. 55(1): p. 126-30.
6.    Baker, L.R., Auto-allergic periaortitis (idiopathic retroperitoneal fibrosis). BJU Int, 2003. 92(7): p. 663-5.
7.    Vaglio, A., C. Salvarani, and C. Buzio, Retroperitoneal fibrosis. Lancet, 2006. 367(9506): p. 241-51.
8.    Corradi, D., et al., Idiopathic retroperitoneal fibrosis: clinicopathologic features and differential diagnosis. Kidney Int, 2007. 72(6): p. 742-53.
9.    Kavoussi, L.R., et al., eds. Campbell-Walsh Urology. 10 ed. Vol. 2. 2012, Elsevier Saunders: Philadelphia, PA. 1108-1112.
10.    Koep, L. and G.D. Zuidema, The clinical significance of retroperitoneal fibrosis. Surgery, 1977. 81(3): p. 250-7.
11.    Amis, E.S., Jr., Retroperitoneal fibrosis. AJR Am J Roentgenol, 1991. 157(2): p. 321-9.
12.    Monev, S., Idiopathic retroperitoneal fibrosis: prompt diagnosis preserves organ function. Cleve Clin J Med, 2002. 69(2): p. 160-6.
13.    Mulligan, S.A., et al., CT and MR imaging in the evaluation of retroperitoneal fibrosis. J Comput Assist Tomogr, 1989. 13(2): p. 277-81.
14.    Vivas, I., et al., Retroperitoneal fibrosis: typical and atypical manifestations. Br J Radiol, 2000. 73(866): p. 214-22.
15.    Kardar, A.H., et al., Steroid therapy for idiopathic retroperitoneal fibrosis: dose and duration. J Urol, 2002. 168(2): p. 550-5.
16.    van Bommel, E.F., et al., Long-term renal and patient outcome in idiopathic retroperitoneal fibrosis treated with prednisone. Am J Kidney Dis, 2007. 49(5): p. 615-25.
17.    Fry, A.C., et al., Successful use of steroids and ureteric stents in 24 patients with idiopathic retroperitoneal fibrosis: a retrospective study. Nephron Clin Pract, 2008. 108(3): p. c213-20.
18.    Marcolongo, R., et al., Immunosuppressive therapy for idiopathic retroperitoneal fibrosis: a retrospective analysis of 26 cases. Am J Med, 2004. 116(3): p. 194-7.
19.    Swartz, R.D., et al., Idiopathic retroperitoneal fibrosis: a role for mycophenolate mofetil. Clin Nephrol, 2008. 69(4): p. 260-8.
20.    Adler, S., et al., Successful mycophenolate mofetil therapy in nine patients with idiopathic retroperitoneal fibrosis. Rheumatology (Oxford), 2008. 47(10): p. 1535-8.
21.    Scheel, P.J., Jr., et al., Combined prednisone and mycophenolate mofetil treatment for retroperitoneal fibrosis. J Urol, 2007. 178(1): p. 140-3; discussion 143-4.
22.    Duchene, D.A., et al., Multi-institutional survey of laparoscopic ureterolysis for retroperitoneal fibrosis. Urology, 2007. 69(6): p. 1017-21.
23.    Stifelman, M.D., et al., Minimally invasive management of retroperitoneal fibrosis. Urology, 2008. 71(2): p. 201-4.
24.    Varkarakis, I.M. and T.W. Jarrett, Retroperitoneal fibrosis. AUA Update Series, 2005. 24.
25.    Elashry, O.M., et al., Ureterolysis for extrinsic ureteral obstruction: a comparison of laparoscopic and open surgical techniques. J Urol, 1996. 156(4): p. 1403-10.
26.    Alexopoulos, E., et al., Idiopathic retroperitoneal fibrosis: a long-term follow-up study. Eur Urol, 1987. 13(5): p. 313-7.



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