Retroperitoneal fibrosis: Report of case and review of literature

WILLIAM E. UTTERER, D.O. A. CARLTON SYLER, Jr., Lox). BRETT C. HON, D O., PH.D. Wichita, Kansas

with sharp, colicky pain in the left lower quadrant of the Among causes of derangement of the abdomen and occasionally in the lower part of the back on kidneys and their draining system, the left side. The patient had experienced urinary fre- retroperitoneal fibrosis is relatively quency and considerable nocturia during the preceding month and had been anorexic for a week. For 12 weeks uncommon. Usually it is idiopathic he had noted cephalalgia on arising. This affected the unless drug abuse is involved, but an frontal area primarily, with posterior radiation. He was increasing number of reports suggest short of breath when he walked two blocks or more or an association with autoimmunity, climbed a flight of stairs. For the past 5 years he had had either as a sporadic event or as the nonspecific pain in the lower part of the back and had result of genetic predisposition. The taken various analgesics for this. He had had surgery of exact mechanism is unknown, the right knee for degenerative arthritis approximately 2 however. In most cases surgical years before. He experienced ankle edema at the end of intervention brings a prompt response the day. He was a thirty pack-year smoker and had been if the diagnosis is made before renal hypertensive for the last 4 months. damage becomes irreversible. When The patient said he had not used methysergide maleate, but during the past 5 years he had taken surgery does not bring a response, the acetaminophen in two formulations, aspirin, caffeine, search for malignant change should be carisoprodol, cephalexin, codeine in two formulations, renewed. The mortality rate is about erythromycin, indomethacin, methocarbamol, orphena- 10 percent when malignancy is not drine citrate, phenacetin in two formulations, and prop- present. oxyphene hydrochloride. He had taken hydralazine for 2 months approximately 5 months earlier. There was no reported use of an ergot preparation or nitrofurantoin and no family history of vascular disease, arthritis, skin rashes, or malignant disease. Physical examination showed him to be alert and well Retroperitoneal fibrosis was mentioned first in oriented, with blood pressure of 200/100 mm. Hg. His English medical literature by Ormond, who re- temperature was 37.7 C. orally, the pulse 100 per minute, and the respiratory rate 20 per minute. The patient had a ported two cases in 1948. Approximately 500 cases positive hepatojugular reflex. Respirations were sym- of this enigmatic disease have been reported since metric, and coarse breath sounds were heard especially Al barran 2 described it in 1905. Although the near the bases of the lungs. The heart rate and rhythm idiopathic form is thought to be the predominant were regular. The abdomen showed obesity and slight type, Ormond3 suggested that the condition may be tension, with tenderness in the left lower quadrant but a tissue response to a chemical acting as a haptene. no definite organomegaly. The patient had an easily re- In some cases retroperitoneal fibrosis occurs con- ducible ventral hernia in the midline just above the um- comitantly with fibrosis in other structures, such bilicus. There were marked tenderness in the costover- as the thyroid gland, orbit, biliary system, medias- tebral angle on the left side and mild nonpitting pretibial tinum, mesentery, and various blood vessels. This edema. Chronic tenosynovitis was present on the dorsum distribution prompted Binder and colleagues to of the left wrist. adopt the term "systemic idiopathic fibrosis," At admission, the blood count showed 4,150,000 eryth- rocytes, 12.2 grams hemoglobin, 36 percent hematocrit, which was suggested by Mitchinson. 5 The purpose and 6,400 leukocytes, with a normal differential count of this paper is to summarize the literature and and Wintrobe indices. The erythrocyte sedimentation report a recent case. rate was 50 mm./hour. The serum showed sodium 143 mEq/L., potassium 5.3 mEq/L., chloride 114 mEq/L., and Report of case carbon dioxide 17 mEq/L. Chemical studies of the blood A 48-year-old black man was admitted to the hospital showed urea nitrogen (BUN) 75 mg./100 ml., creatinine

llfit 86 Retroperitoneal fibrosis results. Levels of extractable nuclear antibodies were not detectable. The CO component of the complement system was 45 mg. 100 ml., and the C3 component 122 mg./100 ml. The prothromhin time was 12.4 sec- onds with a control of 11.5 seconds, and the partial thromboplastin time was 24 seconds with a control of 30 seconds. Cultures of blood and urine were nonproductive. The specific gravity of the urine was 1.005 and the pH 5.4. Urinalysis gave normal results. A sickle-cell prepa- ration gave negative results. Determinations of osmolal- ity showed 318 mOsm/L. in serum and 206 mOsmL. in urine. Cytologic study of the first morning urine specimen showed no abnormal cells. An electrocardio- gram revealed sinus tachycardia and left ventricular hypertrophy. Serum protein electrophoresis gave normal results. Roentgenograms of the chest and abdomen were normal. A renal sonogram showed a pattern suggestive of bilateral obstruction of the outflow tract of the kidney. A renal scan utilizing Tc99m Renotec disclosed poor up- take by the right kidney suggestive of renal insuffi- ciency. An intravenous pyelogram showed a calcific hand surrounding the middle third of the right ureter. A retro- grade pyelogram displayed a split renal pelvis on the right side, bilateral hydronephrosis without medial de- viation of the ureters, and an obstruction in the right Fig. 1. Retrograde pyelogram showing split renal pelvis on right ureter at the level of the fifth lumbar vertebra (Fig. 11. and slight bilateral hydronephrosi.s with obstruction in right ureter at level of L4-L5 intersnace. Laparotomy was performed and showed considerable retroperitoneal fibrosis involving the ureters bilaterally. This began just below the level of the renal pelvis and extended down to the brim of the pelvis. Thickening about the ureters measured approximately 1 cm. in its greatest dimension, and the ureters were encased in a fibrotic sheath, from which the ureters were freed easily. The ureters were repositioned intraperitoneally at a po- sition lateral to the fibrotic tissue. Pathologic study of the biopsy specimen showed fib- romembranous tissue grossly and fibrous connective tis- sue with a moderate inflammatory infiltrate composed primarily of lymphocytes microscopically ( Fig. 2).

Comment Retroperitoneal fibrosis, as the name implies, re- sults from formation of fibrotic tissue in the re- troperitoneal space. This results in entrapment of Fig. 2. Photomicrograph of tissue removed at surgery, showing fibrous change in connectaw tissue and/or moderate lympho- the tubular structures in the retroperitoneum. eyrie infiltrate 1 .250). Recently, Kerr and associates" described the pathologic appearance in fifteen cases. The fibrotic lesion usually extends about the promontory of the 8.5 mg./100 ml., glucose 101 mg., 100 ml., cholesterol 205 sacrum and then to a point just lateral to the uret- m.g/100 ml., triglycerides 122 mg.. 100 ml.. and alkaline ers. Cephalad, it may extend to a variable height, phosphatase 6.3 units. A 24-hour determination of cre- hut usually no higher than the pelvis of the kidney, atining clearance showed 16.4 mm. minute. Enzyme although mediastinal involvement has been re- levels in the serum were glutamic oxalacetic trans- ported. Usually the process is bilateral." aminase 10 I.U./L., lactic dehydrogenase 194 I.U. L. The thickness of fibrotic tissue may range from 2 and creatine phosphokinase 138 I.U. L. Total hilirubin to 12 cm.. and there is great variability with respect in the serum was 0.4 mg.100 ml.. amylase 79 Somogyi units/100 ml., uric acid 9.5 mg. 100 ml., total protein to the presence of tissue and the inflammatory 6.4 grams/100 ml., and albumin 3.4 grams 100 ml. Tests reaction." It has been postulated that the process for antinuclear, antimitochondrial. and antismooth begins near the midline, and soft tissue struc- muscle antibodies and rheumatoid factor gave negative tures eventually surround the tubular structures

On POSO.Inurnal of A ■A 117 57 of the retroperitoneum. 9 Recently, Catino and col- bances in urination may be noted when the disease leagues" observed that fibrotic tissue encompass- is severe. ing the aorta was histologically more mature than Physical examination frequently is not product- similar tissue occurring peripherally. They con- ive. The most common physical sign, noted in less cluded that the process extends from midline to than 10 percent of cases, is an abdominal mass. periphery. Hypertension, anuria, fever, and rectal masses also Histologically, the fibrotic tissue reveals in- have been reported. flammatory cells with proliferating fibroblasts, the Azotemia ( BUN more than 30 mg./100 ml.) is the proportion of which varies. Serial sections within most common laboratory derangement and has the same specimen may show various stages of been detected in 55 percent of cases." In 23 percent maturity, evidenced by mitotic figures and the re- of cases reviewed by Koep and Zuidema" there was sponse to cytoplasmic histochemical staining. no laboratory abnormality. Anemia, an increase in With inactive disease there are widespread erythrocyte sedimentation rate, and polyuria have hyalinization and dense collagen deposits. There been reported." are few or no cells, and vascularity is moderate. Intravenous or retrograde pyelography shows Calcifications are not unexpected. Perineural and bilateral hydronephrosis in approximately two periadiposal deposits predominate. Granulomas, thirds of cases." Unilateral hydronephrosis is seen giant cells, necrosis, and active vasculitis usually in 20 percent." Medial deviation of the ureter was are not present." proposed by Hoffman and Trippel" as a criterion At the other end of the spectrum is an active for the diagnosis of retroperitoneal fibrosis. It was inflammatory process characterized predomi- considered to be a reliable sign of fibrotic entrap- nantly by round cell infiltrates and a few fibro- ment of the ureter, yet it has been reported alone in blasts. Capillary proliferation is widespread, and only 4 percent of cases." Retrograde urography fresh collagen formation can be detected biochemi- may be required, as in the case reported by Cohen cally. and associates. 15 Usually retrograde catheteriza- The gross specimen is usually dense and some- tion is not prevented by the fibrotic lesion, and what rubbery and shows a predilection of the dis- secondary improvement of renal drainage may be ease for the region about the sacrum. observed. Sonography and computed tomographic Arterial involvement usually is not evident clin- (CT) scanning have been used with apparent suc- ically because of the relative resistance of the cess.6 Clouse and associates demonstrated that structures to compression. Ureters, on the other dilatation and obstruction of the lymphatic system hand, are straightened, narrowed, and relatively especially opposite the third lumbar vertebra is aperistaltic, and may be deviated medially. often a helpful sign, but lymphangiography, Ormond" described three stages of the disease venography, arteriography, renal sonography, and on the basis of progression of the pathologic pro- CT scanning do not obviate the need for tissue cess. This division may be helpful in clinical man- diagnosis. Exploration and biopsy of multiple tis- agement. His division follows: sue specimens are essential to the diagnosis except when there is a definite history of prolonged inges- 1) the period of the incidence and development of the under- lying process.. . tion of methysergide. ( 2) the period of the activity and spread of the fibrosis and the In most cases retroperitoneal fibrosis has es- envelopment of the retroperitoneal structures; and, caped etiologic classification. According to Koep (3) the period of contracture of the fibrous mass, like that of a scar, with compression of the enveloped structures. and Zuidema," in two thirds of cases the condition is idiopathic. Some evidence has pointed to the role The disease usually affects persons in the fifth or of methysergide maleate, but a positive drug his- sixth decade, but may occur between the ages of 20 tory has been elicited in only 12 percent of reported and 70. Male patients have been reported to pre- cases. Graham and colleaguess reported 1 percent dominate in a ratio of 2 to 1 on the basis of a large incidence of chronic use of methysergide maleate retrospective study," but recent reports based on among patients with retroperitoneal fibrosis. How- significantly smaller samples have challenged this ever, the dosage and duration of therapy may have statistic. No reliable data on racial predominance been excessive by current standards. Suby and as- have been reported. sociates s hypothesized that methysergide maleate The most common symptom is pain, most fre- acts as a haptene and causes connective tissue fib- quently in the back but sometimes in the flank. rosis secondarily. Ergot alkaloids may induce fib- However, generalized abdominal pain may be the rosis.20 An association of retroperitoneal fibrosis only presenting complaint. Occasionally, weight with carcinoid syndrome has been made, suggest- loss, nausea, vomiting, and malaise occur. Distur- ing that the fibrosis may be the result of serotonin,

118/88 Retroperitoneal fibrosis which is related chemically to the ergot prepa- possibility of immunologic cross reactivity between rations.2 Hydralazine, an analog of serotonin, may host and invader. Host cell antigens may provide provoke the same reaction. Localized fibrosis and receptor sites for these organisms. The possibility ureteral stricture have been attributed to chronic that the HLA system is linked to genes concerned analgesic abuse.21 with the immune response cannot be discounted. Mitchinson 5 suggested on the basis of forty cases HLA-B27 antigen was first linked to retroperi- in which the fibrosis was largely perivascular, that toneal fibrosis by Olsson. 2° This antigen has been trauma to the aortic wall may be the essential associated statistically with connective tissue dis- inciting event. eases in which evidence of aortitis can be found. In cases in which retroperitoneal fibrosis is asso- Mention has been made of the possibility of antece- ciated with long-standing infection of the urinary dent aortitis in retroperitoneal fibrosis. Fibrosis of tract, the name periureteritis plastica has been the upper lobes of the lungs has been documented used.22.23 In these cases the lesion not only was with ankylosing spondylitis33 and the incidence of periureteral but had occurred within the ureteral pneumoconiosis in asbestos workers has been in- wall structures themselves. At surgery, the ureters creased when HLA-B27 antigen was present.34 could not be shelled out as is typically possible. Willscher and associates 32 strengthened the evi- Phills and associates24 reported three cases of re- dence for this association with their report of a troperitoneal fibrosis with sickle-cell trait. They second case of retroperitoneal fibrosis in a black described a major lesion as a "hose-like fibrous man with a positive reaction for HLA-B27 antigen. sheath." In 2 of 3 patients there was renal medul- They recommended HLA typing especially of black lary necrosis. patients who manifest retroperitoneal fibrosis, Lewis and colleagues25 recently reported two since steroid medication in management of the cases in which they suggested that retroperitoneal condition in these patients can be theoretically fibrosis was secondary to long-standing ingestion supported. of an analgesic. They commented that renal papil- Rarely, retroperitoneal fibrosis has been noted as lary necrosis may occur in patients with sickle-cell a localized manifestation of a more widespread or anemia and in those with phenacetin nephropathy "systemic" fibrosis. Coexistent mediastinal fibrosis and expressed the opinion that a renal papillary has been described in sixteen cases, and gen- lesion should be considered as an etiologic agent. eralized mesenteric fibrosis in ten." Sclerosing Hellstrom and Perez-Stable26 reported changes cholangitis, Riedels struma, pseudotumor of the consistent with polyarteritis nodosa in a few pa- orbit, diffuse xanthofibrosis, pleural fibrosis, and tients with retroperitoneal fibrosis. Que and Man- Dupuytrens contracture are among the other "fib- dema27 reported the association of this fibrosis with rotic" conditions with which retroperitoneal fib- Raynauds disease, and Lipman and colleagues28 rosis has been observed." When present, the fib- discussed this association and that with systemic rosis usually coexists with retroperitoneal fibrosis. lupus erythematosus and disseminated vasculitis This association, if any, is still open to conjecture. and suggested that the fibrosis may be a mixed Malignant disease often is mistaken for re- connective tissue disease. Occasionally, antibodies troperitoneal fibrosis. Koep and Zuidema 11 re- to smooth muscle and antinuclear antibodies as ported that in 8 percent of cases there was con- well as abnormalities of A and B globulins have comitant malignancy. At times the diagnosis of been noted. Recently, Katz and associates29 re- idiopathic retroperitoneal fibrosis must be revised ported a case of retroperitoneal fibrosis with im- when neoplasia is discovered. This underscores the mune complex glomerulonephritis. need for constant vigilance. Moreover, multiple The possibility of a genetic predisposition was biopsy specimens should be obtained, since neop- suggested by discovery of two brothers with combi- lasia has been diagnosed as late as 10 years after nations of retroperitoneal fibrosis and other man- retroperitoneal fibrosis was diagnosed. At present, ifestations of fibrosis. 3° Palmer and colleagues31 the histologic pattern of such neoplasia cannot be reported a case of retroperitoneal fibrosis with predicted nor is any group of patients at particular al antitrypsin deficiency. Additional genetic and risk. immunologic evidence was provided by the as- Many patients have had antecedent abdominal sociation of the major histocompatibility antigen and retroperitoneal surgery, trauma, aneurysmal HLA-B27 with retroperitoneal fibrosis.32 dilatation with leakage, thrombophlebitis, or in- Histocompatibility antigens have been linked flammatory disease of the bowel before develop- with an expanding number of diseases. These HLA ment of retroperitoneal fibrosis. It may be specu- antigens show a chemical resemblance to mem- lated that any or all components or metabolites brane antigens of microorganisms and suggest the of blood or urine may be involved in the patho-

Oct. 1980/Journal of AOA/vol. 80/no. 2 119i89 logic process as the result of tissue irritation. ureteral drainage may be attempted via catheters, In the case reported here the patient was a which usually may be placed easily through the middle-aged black man with hypertension and fibrotic areas of the ureter. When the condition is tenderness in the abdomen and flank. Laboratory resistant, nephrostomy may be required. studies showed renal insufficiency, and he had a Definitive surgical treatment requires release of history of approximately 5 years of chronic anal- the ureteral obstruction (ureterolysis). As a rule, gesic ingestion. Prompt progression of the condi- the ureters are freed from their fibrotic encase- tion to an anuric state necessitated introduction ments and repositioned either laterally or in- of ureteral catheters to maintain renal function. traperitoneally to avoid further fibrosis. The sur- Because roentgenologic study showed bilateral in- gical approach is at the midline, since the volvement, a search was made for malignancy or pathologic process is potentially bilateral. More chronic infection. When the patient became depen- than 55 percent of patients have been found at dent on the catheter because of anuria, surgery was surgery to have bilateral involvement. When necessary to maintain renal function and confirm treatment is successful, a return of peristalsis may the suspected diagnosis of retroperitoneal fibrosis. be anticipated. Difficulty in freeing the ureters HLA tissue typing was not performed. While the surgically or the failure to perceive peristalsis once use of steroid preparations may be of theoretical they have been freed should prompt a renewed benefit in patients with HLA-B27 antigen, statisti- search for neoplasia. Otherwise, the inappropriate cally significant proof of this benefit is lacking. diagnosis of fibrosis may result when a neoplasm is Although benefit may be derived from steroid use accessible to therapy. Excision of the entire fibrotic for mild retroperitoneal fibrosis without com- process is unnecessary and seldom technically fea- promise of renal function, steroids probably should sible. play a minor role in treatment when surgical inter- The prognosis is fair in the absence of malig- vention is necessary to prevent progressive deteri- nancy. The total cumulative mortality rate is ap- oration of renal function. proximately 9 percent." The prognosis becomes Because some anecdotal reports in the litera- less favorable as the fibrosis extends beyond the ture2 .25 suggest an association between chronic retroperitoneum. ingestion of analgesics, particularly phenacetin, and retroperitoneal fibrosis, we directed corre- spondence to the pharmaceutical houses that man- 1. Ormond, J.K.: Bilateral ureteral obstruction due to envelopment and ufacture medicines with which the patient had compression by an inflammatory retroperitoneal process. J Urol been treated. We advised them of the possible asso- 59:1072-9, Jun 48 2. Albarran, J.: Liberation externe de luretere. Ann Soc Med-Chir Liege ciation between analgesics and fibrosis and re- 44:328, 1905 quested that they supply us any relevant informa- 3. Ormond, J.K.: Idiopathic retroperitoneal fibrosis. A discussion of the tion. At the time of this report, no manufacturer etiology. J Urol 94:385-90, Oct 65 4. Binder, S.C., et al.: Systemic idiopathic fibrosis. Report of a case of the had been able to confirm such an association, nor concomitant occurrence of retractile mesenteritis and retroperitoneal had they been previously advised of such a case. fibrosis. Am J Surg 124:422-30, Sep 72 We believe therefore that when retroperitoneal 5. Mitchinson, M.J.: The pathology of idiopathic retroperitoneal fibrosis. J Clin Pathol 23:681-9, Nov 70 fibrosis is suspected, a detailed drug history should 6. Kerr, W.S., Jr., et al.: Idiopathic retroperitoneal fibrosis. Clinical include a search for excessive use of analgesics. experiences with 15 cases, 1956-1967. J Urol 99:575-84, May 68 7. Buckberg, G.D., Dilley, R.B., and Longmire, W.P., Jr.: The protean manifestations of sclerosing fibrosis. Surg Gynecol Obstet 123:729-36, Treatment Oct 66 When there is a positive history of ingestion of any 8. Wagenknecht, L.V., and Auvert, J.: Symptoms and diagnosis of re- drug which has been reported to cause re- troperitoneal fibrosis. Analysis of 31 cases. Urol Int 26:185-95, 1971 9. Longmire, W.P., Goodwin, W.E., and Buckberg, G.D.: Management of troperitoneal fibrosis, the drug should be discon- sclerosing fibrosis of the mediastinal and retroperitoneal areas. Ann Surg tinued promptly. A favorable response has been 165:1013-22, Jun 67 10. Catino, D., Torack, R.M., and Hagstrom, J.W.C.: Idiopathic re- noted frequently. troperitoneal fibrosis. Histochemical evidence for lateral spread of the The use of steroids has been advocated, particu- process from the midline. J Urol 98:191-4, Aug 67 larly for early disease even if surgery is anti- 11. Koep, L., and Zuidema, G.D.: The clinical significance of re- troperitoneal fibrosis. Surgery 81:250-7, Mar 77 cipated. These have been of most benefit when 12. Ormond, J.K.: Idiopathic retroperitoneal fibrosis. Ormonds syn- there are severe inflammatory (Stage 2) or gas- drome. Henry Ford Hosp Med Bull 10:13-20, Mar 62 trointestinal changes. Peters 35 recommended a 13. Packham, D.A., and Yates-Bell, J.G.: The symptomatology and diag- nosis of retroperitoneal fibrosis. A review and presentation of case re- daily dose of 40 mg. of prednisone initially, with ports. Br J Urol 40:207-22, 1968 tapering of the dose by 5 or 10 mg. each week until a 14. Hoffman, W.W., and Trippel, D.H.: Retroperitoneal fibrosis. Etio- minimum of 5 mg. daily is being used. logic considerations. J Urol 86:222-31, Aug 61 15. Cohen, S.M., Eckel, R.W., and Persky, L.: Obstructive pathophysio- With severe azotemia or uremia, temporary logic changes in retroperitoneal fibrosis. Arch Surg 92:695-8, May 66

120190 Retroperitoneal fibrosis 16. Stephens, D.H., et al.: Computed tomography of the retroperitoneal cholangitis, Riedels thyroiditis, and pseudotumor of the orbit may be space. Radiol Clin North Am 15:377-90, Dec 77 different manifestations of a single disease. Ann Intern Med 66:884-92, 17.Clouse, M.E., Fraley, E.E., and Litwin, S.B.: Lymphangiographic cri- May 67 teria for diagnosis of retroperitoneal fibrosis. Radiology 83:1-5, Jul 64 31. Palmer, P.E., Wolfe, H.J., and Kostas, C.-I.: Multisystem fibrosis in 18. Graham, J.R., et al.: Fibrotic disorders associated with methysergide alpha-l-antitrypsin deficiency. Lancet 1:221-2, 28 Jan 78 therapy for headache. N Engl J Med 274:359-68, 17 Feb 66 32. Willscher, M.K., Novicki, D.E., and Cwazka, W.F.: Association of 19. Suby, H.I., et al.: Retroperitoneal fibrosis. A missing link in the HLA-B27 antigen with retroperitoneal fibrosis. J Urol 120:631-3, Nov 78 chain. J Urol 93:144-52, Feb 65 33. Jessamine, A.G.: Upper lung lobe fibrosis in ankylosing spondylitis. 20. Olsson, C.A.: Differential diagnosis. In Case records of Massachu- Can Med Assoc J 98:25-9, 6 Jan 68 setts General Hospital, edited by R.E. Scully, J.J. Galdabini, and B.U. 34. Merchant, J.A., et al.: The HL-A system in asbestos workers. Br Med McNeely. N Engl J Med 294:712-8, 25 Mar 76 J 1:189-91, 25 Jan 75 21. Curtis, J.R.: Diseases of the urinary system. Drug-induced renal 35. Peters, P.C.: Retroperitoneal fibrosis. In Urologic surgery, edited by disorders. H. Br Med J 2:375-7, 6 Aug 77 J.F. Glenn. Ed. 2. Harper Row, Hagerstown, Md., 1975 22. Vest, S.A., and Barelare, B., Jr.: Peri-ureteritis plastica. A report of four cases. J Urol 70:38-50, Jul 53 Aach, R.D., Kahn, L.I., and Frech, R.S.: Obstruction of the small intestine due to retractile mesenteritis. Gastroenterology 54:594-8, Apr 67 23. Behrens, M.M., and Holland, J.M.: Periureteritis plastica. Report of a case following staphylococcal infection. J Urol 97:829-32, May 67 Castleman, B., Scully, R.E., and McNeely, B.U., Eds.: Case records of the Massachusetts General Hospital. N Engl J Med 288:254-9, 1 Feb 73 24. Phills, J.A., et al.: Retroperitoneal fibrosis in three siblings with the sickle cell trait. Can Med Assoc J 108:1025-9, 21 Apr 73 25. Lewis, C.T., et al.: Analgesic abuse, ureteric obstruction, and re- troperitoneal fibrosis. Br Med J 2:76-8, 12 Apr 75 Accepted for publication in March 1980. Updating, as necessary, 26. Hellstrom, H.R., and Perez-Stable, E.C.: Retroperitoneal fibrosis has been done by the authors. with disseminated vasculitis and intrahepatic sclerosing cholangitis. Am J Med 40:184-7, Feb 66 27. Que, G.S., and Mandema, E.: A case of idiopathic retroperitoneal From the Department of Internal Medicine, Osteopathic Hospi- fibrosis presenting as a systemic collagen disease. Am J Med 36:320-9, tal of Wichita, Wichita, Kansas. Dr. Syler is the chairman of the Feb 64 department and director of medical education. Dr. Hon is the 28. Lipman, R.L., et al.: Idiopathic retroperitoneal fibrosis and probable director of emergency medicine. Dr. Litterer is in private prac- systemic lupus erythematosus. JAMA 196:1022-4, 13 Jun 66 tice and is a resident in the department of internal medicine at 29. Katz, S.M., et al.: Immune complex glomerulonephritis in a case of St. Michaels Medical Center, Newark, New Jersey, of which Dr. retroperitoneal fibrosis. Am J Clin Pathol 67:436-9, May 77 Leon Smith is the chairman. 30. Comings, D.E., et al.: Familial multifocal fibrosclerosis. Findings Dr. Syler, Osteopathic Hospital of Wichita, 2612 West Central, suggesting that retroperitoneal fibrosis, mediastinal fibrosis, sclerosing Wichita, Kansas 67203.

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