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The Treatment of Osteitis Pubis with Heparin
0022-5347 /81/1254-0528$02.00/0 Vol. 125, April
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1981 by The Williams & Wilkins Co.
THE TREATMENT OF OSTEITIS PUBIS WITH HEPARIN ISRAEL NISSENKORN, CIRO SERVADIO
AND
ERNESTO LUBIN
From the Departments of Urology and Nuclear Medicine, Beilinson Medical Center, Petah Tiqva and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel
ABSTRACT
We treated 7 patients with osteitis pubis by heparinization. Of the 7 patients 2 had a dramatic improvement. Small doses of heparin given routinely preoperatively and postoperatively were not found to prevent the development of osteitis pubis. In view of these results as well as the fact that there presently is no effective method of treatment of this disorder, it is considered justifiable to subject all patients with postoperative osteitis pubis to a therapeutic trial with heparinization. Osteitis pubis is a troublesome complication, occurring in association with an operation in the retropubic or parapubic regions. It generally has been accepted that whether treated or untreated this disease runs a prolonged course of many weeks or even months until it subsides gradually. Conventional antibiotic treatment has been found to be ineffective and the value of steroid treatment remains questionable. Therefore, any promising new approach should be tried. In 1963 Barnes and Malament treated 6 patients suffering from osteitis pubis with phenylbutazone. 1 The response was dramatic in 5 of the 6 patients. To date the literature does not contain reports of further trials using this drug. In 1974 Mynors raised the possi~ bility of treating osteitis pubis by heparinization. 2 During the 4 years since that publication came to our attention we have applied heparinization in 7 cases of osteitis pubis. We herein describe the method of treatment used and the results attained. METHOD OF TREATMENT AND RESULTS
A dosage of 10,000 IU heparin was given intravenously every 6 hours for 5 days. Clotting time was determined 1 hour before each injection. In each case treatment was instituted several days after the diagnosis of osteitis pubis. The osteitis pubis developed after retropubic prostatectomy in 6 patients and after salvage cystectomy in 1 patient performed 6 months after a full dose of irradiation had been given because of stage B2 transitional cell carcinoma of the bladder. In 4 of the 6 patients who had undergone retropubic prostatectomy a urinary fistula had developed above the pubis 1 to 4 days after removal of the catheter from the bladder. One patient had a prolonged, low grade infection in the retropubic space. In 1 patient the postoperative course apparently had been uneventful and this patient had been discharged from the hospital 7 days postoperatively. Six patients were on antibiotic treatment when heparinization was started. Of the 7 patients 5 failed to respond to the 5-day course of heparinization. In these patients steroid treatment was given and recovery was from 3 to 4½ months. In 2 patients there was a dramatic response to heparinization: 1 had undergone salvage cystectomy and 1 had undergone prostatectomy. Relevant data on these 2 patients are presented. CASE REPORTS
Case 1. A 38-year-old man was hospitalized in May 1974 because of silent macroscopic hematuria. The physical examination was unremarkable. An excretory urogram showed no pathological findings but cystoscopy revealed multifocal papillary and sessile tumors. Biopsy disclosed the presence of transitional cell carcinoma infiltrating the deep muscle layer. No distant metastases were found in a subsequent thorough investigation. The patient refused to undergo cystectomy and, thereAccepted for publication June 6, 1980.
528
fore, was referred for irradiation. By the end of June he had received a full dose of 6,000 rad. In September 1974 the patient was hospitalized because of profuse bleeding from the bladder. The hemoglobin level was 6 gm. per cent. After several blood transfusions and repeated unsuccessful attempts to control bleeding by transurethral fulguration and other conservative measures the patient was treated by irrigation of the bladder with 10 per cent formalin for 10 minutes, which led to almost complete cessation of the bleeding within 24 hours. For approximately 6 weeks the patient remained free of hematuria but he had to be rehospitalized in November 1974 because of resumption of the bleeding with a decrease in the hemoglobin level to 6.8 gm. per cent. Lavage of the bladder yielded numerous clots. Repeated attempts to control the bleeding failed and numerous blood transfusions were necessary. A salvage cystectomy was done with diversion of the urine through an ileal conduit. The postoperative course was complicated by a low grade infection in the suprapubic area. The infection subsided gradually and the patient was discharged from the hospital 3 weeks postoperatively. In January 1975 the patient was rehospitalized with a complaint of pelvic and perineal ache spreading to the thighs that made walking almost impossible. The area around the pubic symphysis was tender and there was painful abduction of the thighs. Diagnosis was osteitis pubis and heparinization was instituted as described previously. The improvement was dramatic. After 48 hours of treatment the patient was able to walk with almost no difficulty. After 5 days of treatment he was completely free of the symptoms of osteitis pubis and has remained so. Case 2. A 47-year-old man underwent retropubic prostatectomy. During the 4 months preoperatively an indwelling catheter had been in place. Preoperative urine culture yielded Escherichia coli. Postoperatively, he had a fever up to 38.4C for 10 days, with secretion from the suprapubic . Penrose drain. After antibiotic treatment body temperature returned to normal and the patient was discharged from the hospital 3 weeks postoperatively. Three months later the patient complained of symptoms compatible with osteitis pubis. An x-ray of the pubis failed to reveal any osteolytic changes around the pubic symphysis. A bone scan of the pubic area, made with an indwelling catheter in place so as to keep the bladder empty and, thus, allow visualization of the pubic bone, demonstrated a pathological concentration in this region (see figure). Heparinization led to a dramatic improvement in the condition with no symptoms remaining by the end of the 5-day course of treatment. COMMENT
Millen and Macalister, who list osteitis pubis as a possible complication of prostatectomy, state that whereas the etiology of this condition is obscure it may be considered to be an
TREATMENT OF OSTEITIS PUBIS WITH HEPARIN
Case 2. Bone scan shows pathological concentration in pubic area. Scan was made 24 hours after intravenous injection of 15 me. 99 mtechnetium-methylene diphosphonate with indwelling catheter in place to keep bladder empty and, thus, avoid usual activity in bladder.
infective process with vascular spread. 3 These authors concluded that adequate drainage for 4 days is important and decried the use of a Penrose type of drain. In the years since then we have become but little wiser as to the etiology of this disorder or its treatment, which has remained largely symptomatic. It is evident that the use of suprapubic drainage for ~4 days does not prevent osteitis pubis. Mynors postulated that osteitis pubis primarily is a parapubic venous thrombosis affecting the chondro-osseous tissue of the pubic symphysis and suggested that small doses of heparin given during operation might prevent the development of this condition. 2 Our experience has shown otherwise. During 1977 we administered routinely small doses of heparin (5,000 IU twice daily) on the morning before and during the 4 days after the operation in all patients undergoing operation, as a prophylactic measure against thrombophlebitis. Despite this treatment l patient undergoing retropubic prostatectomy still suffered osteitis pubis. Our experience with 7 patients has yielded no obvious explanation for the rapid response in 2 of them to treatment with heparin, nor for the disappointing failure of the other 5 patients to respond to this treatment. In 1961 Coventry and Mitchell suggested an etiologic classification based on their experience with 45 cases with osteitis pubis. 4 They divided osteitis pubis into 3 types: 1) those patients with true infections and, therefore, not osteitis pubis in the usual sense of the term but a form of osteomyelitis, 2) osteitis pubis that may be a result of infection of the urinary tract, sometimes developing postoperatively, with secondary vascular disturbance and 3) those patients with symptomatic osteitis
529
who have degenerative changes or rheumatoid arthritis involving pelvic joints. We believe that our patients belong rather to the second category as defined by Coventry and Mitchell. What could be the explanation for the dramatic response to heparinization in 2 patients and the lack of response in others? It is believed that no single factor is responsible for the development of osteitis pubis in this category of patients. Three factors seem to appear consistently in the latter type of patient: trauma,5· 6 infection 6 • 7 and stasis of circulation. 5' 8 Since trauma and infection occur rather often during an operation in the retropubic region, especially in urologic patients, why are there not more cases of osteitis pubis? It is believed that the variable factor is the venous stasis. It is conceivable that if the venous drainage from the pubic region is obstructed or thrombophlebitis develops the third factor may be provided and this may set the stage for the development of osteitis pubis. 1 It seems likely that infection of more or less virulent organisms is secondary and, in the presence of venous stasis and devitalized tissue, they are capable of producing a low grade inflammatory reaction. It is possible that only those patients in whom venous stasis is the primary and more important factor respond to heparinization. Presently, we are aware of only 5 patients with osteitis pubis who have been treated with anticoagulants. 2 • 9 Our experience with 7 patients with osteitis pubis treated by heparinization shows successful results in only 2. Contrary to the results reported by Mynors, 2 our own experience with the 7 patients has not been encouraging. However, the dramatic response to heparinization seen in isolated cases and the fact that no more effective treatment presently is available would seem to justify the recommendation that every case of osteitis pubis (once the possibility of a local osteomyelitis has been eliminated) be subjected to a therapeutic trial with heparin. REFERENCES 1. Barnes, W. C. and Malament, M.: Osteitis pubis. Surg., Gynec. &
Obst., 117: 277, 1963. 2. Mynors, J.M.: Osteitis pubis. J. Urol., 112: 664, 1974. 3. Millen, T. and Macalister, C. L. 0.: Retropubic prostatectomy. In: Urology, 3rd ed. Edited by M. F. Campbell and J. H. Harrison. Philadelphia: W. B. Saunders Co., vol. 3, chapt. 63, p. 2517, 1970. 4. Coventry, M. B. and Mitchell, W. C.: Osteitis pubis: observations based on a study of 45 patients. J.A.M.A., 178: 898, 1961. 5. Adams, R. J. and Chandler, F. A.: Osteitis pubis of traumatic etiology. J. Bone Jt. Surg., 35A: 685, 1953. 6. Kirz, E. L.: Osteitis pubis after suprapubic operation of bladder with report of 10 cases. Brit. J. Surg., 34: 272, 1947. 7. Lavalle, L. L. and Hamm, F. C.: Osteitis pubis: its etiology and pathology. J. Urol., 66: 418, 1951. 8. Steinbach, H. L., Petrakis, N. L., Gilfillan, R. S. and Smith, D. R.: The pathogenesis of osteitis pubis. J. Urol., 74: 840, 1955. 9. Holmgren, G. 0. R.: The treatment of osteitis pubis with anticoagulants. A report of three cases in Africans. Cent. Afr. J. Med., 18: 10, 1972.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1981 by The Williams & Wilkins Co.
THE TREATMENT OF OSTEITIS PUBIS WITH HEPARIN ISRAEL NISSENKORN, CIRO SERVADIO
AND
ERNESTO LUBIN
From the Departments of Urology and Nuclear Medicine, Beilinson Medical Center, Petah Tiqva and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel
ABSTRACT
We treated 7 patients with osteitis pubis by heparinization. Of the 7 patients 2 had a dramatic improvement. Small doses of heparin given routinely preoperatively and postoperatively were not found to prevent the development of osteitis pubis. In view of these results as well as the fact that there presently is no effective method of treatment of this disorder, it is considered justifiable to subject all patients with postoperative osteitis pubis to a therapeutic trial with heparinization. Osteitis pubis is a troublesome complication, occurring in association with an operation in the retropubic or parapubic regions. It generally has been accepted that whether treated or untreated this disease runs a prolonged course of many weeks or even months until it subsides gradually. Conventional antibiotic treatment has been found to be ineffective and the value of steroid treatment remains questionable. Therefore, any promising new approach should be tried. In 1963 Barnes and Malament treated 6 patients suffering from osteitis pubis with phenylbutazone. 1 The response was dramatic in 5 of the 6 patients. To date the literature does not contain reports of further trials using this drug. In 1974 Mynors raised the possi~ bility of treating osteitis pubis by heparinization. 2 During the 4 years since that publication came to our attention we have applied heparinization in 7 cases of osteitis pubis. We herein describe the method of treatment used and the results attained. METHOD OF TREATMENT AND RESULTS
A dosage of 10,000 IU heparin was given intravenously every 6 hours for 5 days. Clotting time was determined 1 hour before each injection. In each case treatment was instituted several days after the diagnosis of osteitis pubis. The osteitis pubis developed after retropubic prostatectomy in 6 patients and after salvage cystectomy in 1 patient performed 6 months after a full dose of irradiation had been given because of stage B2 transitional cell carcinoma of the bladder. In 4 of the 6 patients who had undergone retropubic prostatectomy a urinary fistula had developed above the pubis 1 to 4 days after removal of the catheter from the bladder. One patient had a prolonged, low grade infection in the retropubic space. In 1 patient the postoperative course apparently had been uneventful and this patient had been discharged from the hospital 7 days postoperatively. Six patients were on antibiotic treatment when heparinization was started. Of the 7 patients 5 failed to respond to the 5-day course of heparinization. In these patients steroid treatment was given and recovery was from 3 to 4½ months. In 2 patients there was a dramatic response to heparinization: 1 had undergone salvage cystectomy and 1 had undergone prostatectomy. Relevant data on these 2 patients are presented. CASE REPORTS
Case 1. A 38-year-old man was hospitalized in May 1974 because of silent macroscopic hematuria. The physical examination was unremarkable. An excretory urogram showed no pathological findings but cystoscopy revealed multifocal papillary and sessile tumors. Biopsy disclosed the presence of transitional cell carcinoma infiltrating the deep muscle layer. No distant metastases were found in a subsequent thorough investigation. The patient refused to undergo cystectomy and, thereAccepted for publication June 6, 1980.
528
fore, was referred for irradiation. By the end of June he had received a full dose of 6,000 rad. In September 1974 the patient was hospitalized because of profuse bleeding from the bladder. The hemoglobin level was 6 gm. per cent. After several blood transfusions and repeated unsuccessful attempts to control bleeding by transurethral fulguration and other conservative measures the patient was treated by irrigation of the bladder with 10 per cent formalin for 10 minutes, which led to almost complete cessation of the bleeding within 24 hours. For approximately 6 weeks the patient remained free of hematuria but he had to be rehospitalized in November 1974 because of resumption of the bleeding with a decrease in the hemoglobin level to 6.8 gm. per cent. Lavage of the bladder yielded numerous clots. Repeated attempts to control the bleeding failed and numerous blood transfusions were necessary. A salvage cystectomy was done with diversion of the urine through an ileal conduit. The postoperative course was complicated by a low grade infection in the suprapubic area. The infection subsided gradually and the patient was discharged from the hospital 3 weeks postoperatively. In January 1975 the patient was rehospitalized with a complaint of pelvic and perineal ache spreading to the thighs that made walking almost impossible. The area around the pubic symphysis was tender and there was painful abduction of the thighs. Diagnosis was osteitis pubis and heparinization was instituted as described previously. The improvement was dramatic. After 48 hours of treatment the patient was able to walk with almost no difficulty. After 5 days of treatment he was completely free of the symptoms of osteitis pubis and has remained so. Case 2. A 47-year-old man underwent retropubic prostatectomy. During the 4 months preoperatively an indwelling catheter had been in place. Preoperative urine culture yielded Escherichia coli. Postoperatively, he had a fever up to 38.4C for 10 days, with secretion from the suprapubic . Penrose drain. After antibiotic treatment body temperature returned to normal and the patient was discharged from the hospital 3 weeks postoperatively. Three months later the patient complained of symptoms compatible with osteitis pubis. An x-ray of the pubis failed to reveal any osteolytic changes around the pubic symphysis. A bone scan of the pubic area, made with an indwelling catheter in place so as to keep the bladder empty and, thus, allow visualization of the pubic bone, demonstrated a pathological concentration in this region (see figure). Heparinization led to a dramatic improvement in the condition with no symptoms remaining by the end of the 5-day course of treatment. COMMENT
Millen and Macalister, who list osteitis pubis as a possible complication of prostatectomy, state that whereas the etiology of this condition is obscure it may be considered to be an
TREATMENT OF OSTEITIS PUBIS WITH HEPARIN
Case 2. Bone scan shows pathological concentration in pubic area. Scan was made 24 hours after intravenous injection of 15 me. 99 mtechnetium-methylene diphosphonate with indwelling catheter in place to keep bladder empty and, thus, avoid usual activity in bladder.
infective process with vascular spread. 3 These authors concluded that adequate drainage for 4 days is important and decried the use of a Penrose type of drain. In the years since then we have become but little wiser as to the etiology of this disorder or its treatment, which has remained largely symptomatic. It is evident that the use of suprapubic drainage for ~4 days does not prevent osteitis pubis. Mynors postulated that osteitis pubis primarily is a parapubic venous thrombosis affecting the chondro-osseous tissue of the pubic symphysis and suggested that small doses of heparin given during operation might prevent the development of this condition. 2 Our experience has shown otherwise. During 1977 we administered routinely small doses of heparin (5,000 IU twice daily) on the morning before and during the 4 days after the operation in all patients undergoing operation, as a prophylactic measure against thrombophlebitis. Despite this treatment l patient undergoing retropubic prostatectomy still suffered osteitis pubis. Our experience with 7 patients has yielded no obvious explanation for the rapid response in 2 of them to treatment with heparin, nor for the disappointing failure of the other 5 patients to respond to this treatment. In 1961 Coventry and Mitchell suggested an etiologic classification based on their experience with 45 cases with osteitis pubis. 4 They divided osteitis pubis into 3 types: 1) those patients with true infections and, therefore, not osteitis pubis in the usual sense of the term but a form of osteomyelitis, 2) osteitis pubis that may be a result of infection of the urinary tract, sometimes developing postoperatively, with secondary vascular disturbance and 3) those patients with symptomatic osteitis
529
who have degenerative changes or rheumatoid arthritis involving pelvic joints. We believe that our patients belong rather to the second category as defined by Coventry and Mitchell. What could be the explanation for the dramatic response to heparinization in 2 patients and the lack of response in others? It is believed that no single factor is responsible for the development of osteitis pubis in this category of patients. Three factors seem to appear consistently in the latter type of patient: trauma,5· 6 infection 6 • 7 and stasis of circulation. 5' 8 Since trauma and infection occur rather often during an operation in the retropubic region, especially in urologic patients, why are there not more cases of osteitis pubis? It is believed that the variable factor is the venous stasis. It is conceivable that if the venous drainage from the pubic region is obstructed or thrombophlebitis develops the third factor may be provided and this may set the stage for the development of osteitis pubis. 1 It seems likely that infection of more or less virulent organisms is secondary and, in the presence of venous stasis and devitalized tissue, they are capable of producing a low grade inflammatory reaction. It is possible that only those patients in whom venous stasis is the primary and more important factor respond to heparinization. Presently, we are aware of only 5 patients with osteitis pubis who have been treated with anticoagulants. 2 • 9 Our experience with 7 patients with osteitis pubis treated by heparinization shows successful results in only 2. Contrary to the results reported by Mynors, 2 our own experience with the 7 patients has not been encouraging. However, the dramatic response to heparinization seen in isolated cases and the fact that no more effective treatment presently is available would seem to justify the recommendation that every case of osteitis pubis (once the possibility of a local osteomyelitis has been eliminated) be subjected to a therapeutic trial with heparin. REFERENCES 1. Barnes, W. C. and Malament, M.: Osteitis pubis. Surg., Gynec. &
Obst., 117: 277, 1963. 2. Mynors, J.M.: Osteitis pubis. J. Urol., 112: 664, 1974. 3. Millen, T. and Macalister, C. L. 0.: Retropubic prostatectomy. In: Urology, 3rd ed. Edited by M. F. Campbell and J. H. Harrison. Philadelphia: W. B. Saunders Co., vol. 3, chapt. 63, p. 2517, 1970. 4. Coventry, M. B. and Mitchell, W. C.: Osteitis pubis: observations based on a study of 45 patients. J.A.M.A., 178: 898, 1961. 5. Adams, R. J. and Chandler, F. A.: Osteitis pubis of traumatic etiology. J. Bone Jt. Surg., 35A: 685, 1953. 6. Kirz, E. L.: Osteitis pubis after suprapubic operation of bladder with report of 10 cases. Brit. J. Surg., 34: 272, 1947. 7. Lavalle, L. L. and Hamm, F. C.: Osteitis pubis: its etiology and pathology. J. Urol., 66: 418, 1951. 8. Steinbach, H. L., Petrakis, N. L., Gilfillan, R. S. and Smith, D. R.: The pathogenesis of osteitis pubis. J. Urol., 74: 840, 1955. 9. Holmgren, G. 0. R.: The treatment of osteitis pubis with anticoagulants. A report of three cases in Africans. Cent. Afr. J. Med., 18: 10, 1972.