Excerpt from Retroperitoneal Fibrosis

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Background

The French urologist Albarran first described retroperitoneal fibrosis (RPF) in 1905,¹ but with Ormond's publication in 1948,² the disease became an established clinical entity.

In most patients (approximately 68%), no etiologic factor is found. Therefore, the term idiopathic RFP is used. Evidence suggests that RPF is an autoimmune response to an insoluble lipid called ceroid that has leaked through a thinned arterial wall from atheromatous plaques.^{3, 4} Other implicated causes include drugs, abdominal aortic aneurysm, ureteric renal injury, infection, retroperitoneal malignancy, postirradiation therapy, chemotherapy and hemilaminectomy, hypothyroidism and carcinoid tumor. No genetic predominance is seen in malignant retroperitoneal fibrosis.^{5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15}

RPF can be diagnosed on the basis of the history and the radiologic observations. At times, the diagnosis is not established firmly until surgical exploration. The use of steroids in RPF remains controversial; however, some authors believe that steroids can be used as an adjuvant to surgical ureterolysis. Immunosuppressive drugs, such as azathioprine, cyclophosphamide, and tamoxifen, have been used to treat RPF.^{16, 17, 18, 19, 20, 21, 22}

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Pathophysiology

Grossly, RPF appears as an exuberant mass of white, woody, fibrous tissue covering the retroperitoneal structures such as the aorta, vena cava, ureters, and psoas muscle. It may extend from the renal pedicle to below the pelvic brim. The center of the plaque is usually located at the level of the fourth or fifth lumbar vertebra, overlying the aortic bifurcation. Not uncommonly, the fibrous tissue bifurcates and follows the common iliac arteries. Rarely, the fibrous process extends into the root of the mesentery or passes through the crura of the diaphragm to continue as fibrous mediastinitis.

Histologically, the predominant finding is a fibrous tissue consisting of collagen fibrils and fibroblasts. A subacute nonspecific inflammatory reaction is often present, or completely hyalinized fibrosis may be the only finding. The cellular infiltrate includes polymorphonuclear cells, lymphocytes, eosinophils, or plasma cells. In the chronic phase, the only finding may be an acellular fibrosis.

The coexistence of RPF with primary biliary cirrhosis, fibrosing mediastinitis, panhypopituitarism, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus (SLE), polyarteritis nodosa, ankylosing spondylitis, and Riedel²³ or Hashimoto thyroiditis support the hypothesis of an immune-mediated mechanism.

The association of RPF with the prolonged use of certain drugs and with the improvement of clinical symptoms (in most instances after cessation of the drug therapy) indicates that the fibrotic process is the end stage of vasculitis resulting from a hypersensitivity reaction to various antigens such as drugs and diseases. Drugs implicated in causing RPF include methysergide, beta-adrenergic blockers, lysergic acid diethylamide, methyldopa, amphetamines, phenacetin, pergolide (withdrawn from US market March 29, 2007), and cocaine.

Frequency

United States

The overall incidence in the United States appears to be the same as that found internationally.

International

RPF is relatively uncommon, with an incidence of 1 case per 200,000 population.

Mortality/Morbidity

Although fatalities do occur, a satisfactory outcome can be expected if renal impairment is not too severe.

• Unlike idiopathic (nonmalignant) RPF, a distinctly poor prognosis is associated with malignant RPF, which occurs in response to metastatic tumor cells in the retroperitoneum.
• Most patients live only 3-6 months after receiving a diagnosis of malignant RPF, although prolonged survival has been reported. Close follow-up care is critically important to ensure the absence of progressive or recurrent disease.

Race

No racial preponderance has been recorded.

Sex

The disease is 3 times more common in males than in females; however, methysergide-related RPF has a female-to-male ratio of 2:1. No sex predominance is noted in malignant RPF.

Age

• The age range of patients is 7-85 years, with predominance in patients aged 40-60 years.
• RPF in children has been reported in the literature.
• One case has been reported in a stillborn fetus.

Anatomy

The retroperitoneum is a large space bounded anteriorly by the posterior parietal peritoneum, posteriorly by the transversalis fascia, and superiorly by the diaphragm. Inferiorly, it extends to the level of the pelvic brim.

On either side, the retroperitoneum is divided into 3 compartments by coronally oriented anterior and posterior renal fascia, which lie anterior and posterior to the kidneys, respectively. The anterior renal fascia is a thin layer of connective tissue, which is difficult to identify on images. The anterior and posterior renal fasciae fuse laterally to form the lateroconal fascia. The lateroconal fascia extends posterolaterally to the ascending and descending colon and fuses with the parietal peritoneum. Superiorly, both layers of renal fasciae blend with the diaphragmatic fascia, and inferiorly, this fuses with the iliac fascia and periureteric connective tissue at the level of the iliac crest. Medially, the anterior renal fascia blends with the connective tissue and fat that surround the great vessels, and the posterior renal fascia blends with the fascia of the psoas and quadratus lumborum muscles.

Each perirenal space, which is situated between the anterior and posterior renal fasciae, contains a kidney, adrenal gland, pelvocalyceal system, proximal ureter, and neurovascular and lymphatic structures. No potential communication exists between the 2 perirenal spaces.

The anterior pararenal space is limited anteriorly by the posterior parietal peritoneum and posteriorly by the anterior renal fascia. The contents are the first, second, and third parts of the duodenum; the pancreas; the ascending colon; the descending colon; and the splenic, hepatic, and proximal superior mesenteric arteries. The anterior pararenal space communicates across the midline.

The posterior pararenal space is bounded anteriorly by the posterior renal fascia and posteriorly by the transversalis fascia. The medial extent of this space is limited by the fusion of posterior renal fascia with the fasciae of the psoas and quadratus lumborum muscles; however, communication with the retrocrural space and, therefore, the mediastinum is possible. Laterally, the fat of the posterior pararenal space continues as the properitoneal fat stripe. The posterior pararenal space contains no organs. The anterior and posterior pararenal spaces communicate along their inferior margin.

Clinical Details

Most patients present with nonspecific symptoms of less than 12 months' duration. Children may present with hip or gluteal pain.^{24, 25, 26}

In the early stage, signs and symptoms originate from the disease process; in the advanced stage, clinical features represent the effects of obstructive uropathy and renal failure. The most common presentation is pain (92%) occurring in the flank (42%), the back (32%), the scrotum (8%), or the lower abdomen (28%). Other presentations include fever, weight loss (38%), nausea and vomiting (32%), malaise (18%), polyuria (18%), polydipsia (18%), anorexia (15%), nocturia (13%), oliguria (10%), urinary frequency (8%), and hematuria (2%).^{9, 27, 28, 29, 30, 31, 32, 33}

Hypertension is a common clinical feature. The disease has been reported to manifest as constipation and large-bowel and duodenal obstruction. Fibrotic processes can also cause compression of the great vessels, resulting in thrombophlebitis and arterial insufficiency. RPF has been documented to present as jaundice resulting from involvement of the common bile duct and exophthalmos resulting from retro-orbital disease.

RPF can appear at a later stage as a complication of fibrosis. The patient may present with renal failure resulting from ureteric involvement. Venous and lymphatic obstruction may present as lower-limb edema. Claudication may result secondary to arterial insufficiency. Invasion of the duodenum and colon and the common bile duct has been documented as causing bowel obstruction and jaundice, respectively. Neurologic presentation secondary to spinal epidural extension has been reported.^{34, 35}

Idiopathic RPF may rarely involve the thoracic aorta and the origin of its major branches, with a pattern similar to that of other forms of large-vessel vasculitides.³⁶

There is an association between RPF and autoimmune pancreatitis. 

Laboratory findings include anemia, azotemia, and an increased erythrocyte sedimentation rate (ESR). Elevated white cell counts and pyuria can occur. The diagnosis of RPF often is delayed because of its nonspecific presentation.

Preferred Examination

Plain radiographic findings in RPF are nonspecific, and most findings are related to the late complications of fibrosis, such as bowel obstruction and pulmonary edema secondary to renal failure. Contrast-enhanced studies, such as barium follow-through and barium enema examinations, can show the level of bowel obstruction. The diagnosis of RPF has often been suggested on the basis of the excretory urographic findings due to extensive changes in the urinary tract. Retrograde pyelography is used in patients with severely impaired renal function.^{37, 38, 39, 40}

Aortography, venography, and lymphangiography help in assessing the level and extent of occlusion; however, findings from these examinations can be normal in advanced disease.

Ultrasonography can be used as a noninvasive technique. Sonograms may or may not help in identifying the retroperitoneal mass, but they can readily demonstrate the degree of obstruction to the ureters and kidneys. Attempts have been made to differentiate benign RPF from malignant RPF by using color Doppler imaging.

Computed tomography (CT) and magnetic resonance imaging (MRI) provide superior delineation of the extent of the masses of RPF.^{37, 41, 42, 43}

Isotope renography is useful in the serial assessment of renal function. Gallium scintigraphy may demonstrate increased uptake, depending on the activity of inflammation. The use of fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating benign from malignant RPF is promising.^{44, 45}

Limitations of Techniques

Findings on plain radiography and contrast-enhanced studies are nonspecific, demonstrating the late effects of fibrosis. Excretory urography helps in establishing a diagnosis in the early stage of the disease.

Characteristically, medial deviation of the ureter is present, usually at the middle third, beginning at the level of the third or fourth lumbar vertebra. The medial deviation of the ureter is not a constant finding in patients with RPF, and approximately 20% of patients with normal urographic findings have medial deviation of ureters without demonstrable evidence of pathologic change in the urinary tract. Most retroperitoneal neoplasms displace the ureters in a lateral direction, but medial deviation can occur. Other causes for medial displacement of the ureters include aneurysm, metastatic tumors, and bladder diverticulum. Medial displacement may be seen after abdominoperineal resection and removal of pelvic malignancy.

Retrograde pyelography is an invasive technique with no additional value compared with excretory urography.

On sonograms, RPF may appear as a relatively echo-free mass centered on the sacral promontory. Imaging the retroperitoneum may not be possible, particularly in obese patients or in those with excessive bowel gas.

With CT and MRI, the fibrosis can be shown in more detail. The symmetric distribution and geometric shape are highly suggestive of RPF. CT scans may not be helpful in differentiating benign RPF from malignant RPF. MRI may help in differentiating the two, but the diagnosis cannot be certain by using MRI.

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