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Transurethral Surgery in Relation to Bilharziosis of the Bladder
TRANSURETHRAL SURGERY IN RELATION TO BILHARZIOSIS OF THE BLADDER H. R. NEWMAN From All Saint's Hospital for Genito-Urinary Diseases, London, England INCIDENCE
Bilharziosis is a rare disease (in the Western Hemisphere), this being the first case reported from All Saints' Hospital, London, and not a single case has been reported from the Urological Service of New York Post-Graduate Hospital, Columbia University. Bilharziosis, however, is a widely spread disease among the populations of Egypt and South Africa. MacCallum (1913-1915) recorded the incidence of the infestation among the general population of Egypt to range between 10 per cent and 42 per cent. During 1923 and 1924, the incidence of bilharziosis infestation among the inhabitants in different localities in Egypt was ascertained to be as high as 83 per cent of the population of Egypt, and it is at present thought that 70 per cent-80 per cent of the total population is infected, that is, 10 million out of a total population of about 13 million. Theodor Bilharz, in 1851, discovered the vrnrm (Schistosoma haemotobium) which is responsible for the disease. There is proof, however, of the existence of bilharziosis in mummies. (1250-1000 B.C.) The Schistosoma haemotobium most commonly invades the urinary tract, although in 12 per cent of the cases, ova are found in the stool. Infestation with Schistosoma haemotobium is widespread throughout Egypt, while Schistosoma mansoni exists mostly in the Delta and not in upper Egypt. Schistosoma mansoni in about 87 per cent of the cases produces its lesions in the intestinal tract, and in about 4 per cent of cases it is found in the urinary tract. Schistomiasis j aponica is widespread in Eastern Asia, especially Japan and China. The discussion will be limited to bilharziosis of the bladder, caused by the Schistosoma haemotobium. PATHOLOGY
An intermediate host (the snail) plays a vital role in Bilharziosis. Infected snails usually inhabit stagnant streams; individuals bathing in or drinking this water may become infected. The Schistosoma haemotobium cercariae having escaped from the snail into the water may pierce the unbroken skin or mucous membrane of man. Having reached the blood stream, they are carried to the right side of the heart and through the pulmonary vessels into the left side. The adult worm develops in the liver. The pregnant female leaves the liver in the venous circulation to lay her eggs. The richer an organ is in venules the more likely is it to become infected with bilharzia. The commonest organ involved in the genito-urinary tract is the bladder. The site of infection is the trigone in the neighborhood of the ureteric orifices, or in the lower end of the ureters. The female Schistosoma haemotobium lays its ova in the submucous layer of the bladder. Dead ova are absorbed or calcified and act as inert foreign bodies. 440
SURGERY AND BLADDER BILHAHZIOSIS
441
The living ova which are deposited in the submucous layer, superficial to the muscularis mucosa, stimulate the growth of vilharzial granulation tissue in the form of single or multiple papillomata. These papillomata may eventually become malignant. They may obstruct the lower end of the ureters. Most of these growths sooner or later undergo degeneration; either the covering mucous membrane becomes desquamated with the formation of superficial ulcers, or the entire papilloma may break off, leaving an ulcer on the bladder wall. The superficial and deep ulcers may heal with the formation of fibrous tissue or they may become secondarily infected. It is during this stage of ulceration that the bladder is irritable; there is frequency of micturition; bilharzia ova, blood and pus are found in the urine. The disintegrated tissue from papillomata lying free in the bladder is a suitable nucleus for the formation of stone. The ova deposited in the submucous layer of the bladder do not produce a papilloma but a flat submucous lesion. This is, however, subject to the same pathological changeR and complications as the papilloma. SYMPTOMATOLOGY
As the cercariae pierce the skin the patient feels irritation and itching at the involved site. The incubation period of the disease is thought to be 4-8 weeks. The early signs and symptoms are very indefinite, prolonged pyrexia with urticaria being described by many authors. The most outstanding symptom is haematuria. Blood in the urine as a sign of bilharziosis has been known and recognized for many centuries. It is mentioned in the Kahum papyrus of the XII dynasty (Patric and Griffith) and 400 years later in the Ebers papyrus. At a later stage of the disease the hematuria diminishes and symptoms referable to cystitis become much more predominant. Frequency of micturition is intense; urine is passed as many as 100 times during the day and night. The leucocyte count is also significant; usually an eosinophilia of 10 per cent27 per cent is found. X-ray studies of the genito-urinary tract in bilharziosis are helpful as an aid to diagnosis. Calcified ova when in sufficient concentration throw a shadow on the film producing characteristic shadows which are described under such headings as "the cloudy bladder of bilharziosis," "calcified lines and patches of bilharziosis." Calculi are present in a large number of cases of bilharziosis of the genito-urinary tract. They are usually formed in the later stages of the disease and throw the usual shadows on an x-ray film. TREATMENT
Bilharziosis is usually treated by intravenous injections of tartar emetic. This form of therapy was introduced by Christopherson in 1917-18. It has been stressed by Christopherson that the above drug should be given in effective dosage. The clinical results can be gauged by the determination of the presence or absence of the ova in the faeces and urine. The bilharzia parasite seldom resists a complete course of 30 grains given over a period of 4 to 5 weeks. Although the drug is highly toxic, Christopherson in 1927 reports only 7 fatal cases
442
H. R. NEWMAN
among 284,934 cases treated. During the course of treatment patients often complain of dry cough, pain in the chest and discomfort in the throat. A feeling of nausea and severe muscular pains may follow immediately an intravenous injection. Although the general treatment of bilharziosis with intravenous tartar emetic is essential, surgical intervention may be both very important and beneficial in selected cases. In the past, surgical intervention played only a palliative role in the later and final stages of the disease. Lithotomies, vesical, ureteric or renal, were performed, and, in the final stages, the bladder was drained through a perinea! incision in an attempt to alleviate, during the last few months of existence, the intolerable suffering caused by a grossly contracted bladder. After an intravenous injection of tartar emetic the pathological changes in the submucous tissue usually disappear, although, in many cases the lesions remain unaltered. These cases are very often aided by surgical intervention. Dr. Ibrahim Fahny El Minyawy of Cairo, has excised rectal papillomata with gratifying results. It seems rational and feasible to excise early vesical papillomata by means of a resectoscope. Such a procedure might prevent many of the complications such as malignant change, necrosis and infection, continued haemorrhages, etc. CASE REPORT
A male patient, aged 25, came to the out-patient department of All Saints' Hospital complaining of painless intermittent hematuria for the past 11 years. The hematuria which was characterized by the passage of fresh blood occurred as a rule at the end of micturition. There was no history of urinary frequency. This patient had migrated to England from Newcastle, South Africa, and had lived here during the past 5 years. Physical examination revealed nothing of note. The kidneys were not palpable and no tenderness was present. On rectal examination the prostate gland was normal in size and consistency. External genitalia were normal. The chest was normal. The cardio-vascular system was normal. The blood pressure was 130/80. Laboratory Examination: Urine: Alkaline reaction, specific gravity 1013, no albumin or sugar. Centrifuged specimen of urine revealed the presence of amorphous phosphates, 15~20 white blood cells, 5~6 red blood cells per high power field, and ova of schistosoma haemotobium. Culture of the urine was sterile after incubation of 24 hours on routine media. Blood urea: 30 mg. per 100 cc, blood urea concentration 3.0 per cent, 3.0 per cent, 2.8 per cent. X-ray of the abdomen was negative. Cystoscopic examination revealed lesions characteristic of bilharziosis. The bladder capacity was normal, amounting to 12 ounces of fluid. The ureteric orifices were normal. Scattered over the surface of the trigone and to a lesser extent over the vault were whitish, oval and rounded bodies. They were surrounded by areas of congestion. Some of the bodies were arranged in groups and more predominant in the region of the ureteric orifices. These small lesions
SURGERY AND BLADDER BILHARZIOSIS
443
simulated tubercles, but were very glossy in appearance. Immediately above and to the right of the right ureteric orifice a papilloma was located, its base fairly broad and its surface very bright red in colour simulating granulation tissue. The treatment may be summarized under 2 headings: (1) Local treatment, which consists of endoscopic resection of the papilloma; (2) general treatment, which consists of intravenous injections of sodium antimony tartrate. Endoscopic resection of the papilloma was carried out as follows: A low spinal anaesthetic was given using ¾cc stovaine. The anterior urethra was well lubricated by injecting into it very gently 5 cc glycerine, using a Canny Ryall syringe. It was then gradually dilated with steel sounds after which the resectoscope was introduced. Resection was carried out as in operation for prostate obstruction.
Fm. 1. X 195. Granulation tissue from base of bilharzial papilloma of bladder removed endoscopically. In addition to granulation tissue, there is an ovum seen in transverse section, and in this limiting membrane can easily be seen.
The resectoscope used was Millin's modification of the Canny Ryall instrument. The instrument is particularly useful for the resection of growths situated in the posterior half of the bladder. At the conclusion of the operation the bladder was thoroughly irrigated with silver nitrate solution 1: 5000. A soft rubber catheter, No. 24 F., was tied in for 48 hours. The patient made an uneventful recovery. The papilloma resected has been sectioned by Doctor Haler and illustrations are shown herewith (figs. 1, 2, 3). The general treatment consisted of intravenous injections of sodium antimony tartrate. The initial dose given was ½gr., and in each succeeding day the dose was gradually increased by ½gr. until a maximum dose of 2 grains was given daily. On the fourth day of treatment the patient complained of blurring vision and general weakness and remained in bed. On the fifth day of treatment he
444
H. R. NEWMAN
complained of muscular pain confined to the muscles of the neck. No injection was given on the sixth day but the symptoms persisted. On the seventh day the injections were resumed and 1 tablet of vitamin B 1 given 3 times daily (1
FIG. 2. X660. Demonstrating disintegrating ovum, showing pyknosis of nucleus and (?) early calcification of spinous area of ovum.
Frn. 3. X660. Showing active, presumably viable, ovum, with well demonstrated terminal spine and easily visible membrane covering, and so forth.
tablet is equivalent to 1 mg. aneurin 500 international units) (Roche Benerva vitamin B 1). The intravenous injections of 2 grains daily were continued until 27 gr. of sodium antimony tartrate had been given.
SURGERY AND BLADDER BILHARZIOSIS
445
After this patient was placed on vitamin B 1, the toxic symptoms disappeared; he felt well and was able to walk about without any ill effects. Urinalysis at the end of the treatment revealed reaction alkaline, specific gravity 1027, no albumin. No bilharzia! ova were seen. Cystoscopic examination revealed no evidence of a papilloma. There was slight congestion of the trigone. The bladder was practically normal. The patient was discharged with no urinary symptoms. SUMMARY
Bilharziosis of the bladder is a very uncommon disease in England. Schistosoma haemotobium is the commonest causative agent. The pathological lesion consists of a diffuse infiltration of the submucous layer or the formation of papillomata. The papillomata are usually situated in the regions of the ureteric orifices. The earliest symptom is usually intermittent painless hematuria, marked urinary frequency being a very late symptom. Sodium antimony tartrate given intravenously and endoscopic resection of papillomatas in selected cases is the treatment of choice. The value of vitamin B 1 in the control of neuro-muscular symptoms. arising during the administration of sodium antimony tartrate is illustrated in the case described above. I am indebted to Sir William De C. Wheeler for permission to publish this case, and to Dr. D. Haler for his kindness in preparing the slides, and in supplying the microphotographs and their description. REFERENCES BEER, EDWIN: Tumors of the Bladder. Baltimore: Williams & Wilkins Co., 1935. CHRISTOPHERSON, J.B., AND vVARD, R. OGIER: Brit. J. Surg., April, 1934. DIAMANTJS, A.: J. d'urol., Juillet, 1935. IBRABIM. ALY BEY: Congres Internationale de Medicine Tropicale, et d'Hygiene, 1932, n. 4!:19.
MAnnEN. FRANK CoLE: Congres Internationale de Medicine Tropicale, et d'Hygiene, 1932, p. 487. MILLIN. TERENCE: Brit. J. Surg., April, 1937, 25: 245. M TNYAWY, EL IBRAHIM F ARMY: Congres Internationale de ;\1.edicine Tropicale et d'Hygione, 1932, p. 547. RllIYRNIOTIS, P. C.: Congres Internationale de Medicine Tropicale et d'Hygiene, 1932, p. 499. SoROUR, M. F.: Congres Internationale de Medicine Tropicale et d'Hygiene, 1932, p. 321. Young's Practice of Urology. Philadelphia: W. B. Saunders Co., 1926.
Bilharziosis is a rare disease (in the Western Hemisphere), this being the first case reported from All Saints' Hospital, London, and not a single case has been reported from the Urological Service of New York Post-Graduate Hospital, Columbia University. Bilharziosis, however, is a widely spread disease among the populations of Egypt and South Africa. MacCallum (1913-1915) recorded the incidence of the infestation among the general population of Egypt to range between 10 per cent and 42 per cent. During 1923 and 1924, the incidence of bilharziosis infestation among the inhabitants in different localities in Egypt was ascertained to be as high as 83 per cent of the population of Egypt, and it is at present thought that 70 per cent-80 per cent of the total population is infected, that is, 10 million out of a total population of about 13 million. Theodor Bilharz, in 1851, discovered the vrnrm (Schistosoma haemotobium) which is responsible for the disease. There is proof, however, of the existence of bilharziosis in mummies. (1250-1000 B.C.) The Schistosoma haemotobium most commonly invades the urinary tract, although in 12 per cent of the cases, ova are found in the stool. Infestation with Schistosoma haemotobium is widespread throughout Egypt, while Schistosoma mansoni exists mostly in the Delta and not in upper Egypt. Schistosoma mansoni in about 87 per cent of the cases produces its lesions in the intestinal tract, and in about 4 per cent of cases it is found in the urinary tract. Schistomiasis j aponica is widespread in Eastern Asia, especially Japan and China. The discussion will be limited to bilharziosis of the bladder, caused by the Schistosoma haemotobium. PATHOLOGY
An intermediate host (the snail) plays a vital role in Bilharziosis. Infected snails usually inhabit stagnant streams; individuals bathing in or drinking this water may become infected. The Schistosoma haemotobium cercariae having escaped from the snail into the water may pierce the unbroken skin or mucous membrane of man. Having reached the blood stream, they are carried to the right side of the heart and through the pulmonary vessels into the left side. The adult worm develops in the liver. The pregnant female leaves the liver in the venous circulation to lay her eggs. The richer an organ is in venules the more likely is it to become infected with bilharzia. The commonest organ involved in the genito-urinary tract is the bladder. The site of infection is the trigone in the neighborhood of the ureteric orifices, or in the lower end of the ureters. The female Schistosoma haemotobium lays its ova in the submucous layer of the bladder. Dead ova are absorbed or calcified and act as inert foreign bodies. 440
SURGERY AND BLADDER BILHAHZIOSIS
441
The living ova which are deposited in the submucous layer, superficial to the muscularis mucosa, stimulate the growth of vilharzial granulation tissue in the form of single or multiple papillomata. These papillomata may eventually become malignant. They may obstruct the lower end of the ureters. Most of these growths sooner or later undergo degeneration; either the covering mucous membrane becomes desquamated with the formation of superficial ulcers, or the entire papilloma may break off, leaving an ulcer on the bladder wall. The superficial and deep ulcers may heal with the formation of fibrous tissue or they may become secondarily infected. It is during this stage of ulceration that the bladder is irritable; there is frequency of micturition; bilharzia ova, blood and pus are found in the urine. The disintegrated tissue from papillomata lying free in the bladder is a suitable nucleus for the formation of stone. The ova deposited in the submucous layer of the bladder do not produce a papilloma but a flat submucous lesion. This is, however, subject to the same pathological changeR and complications as the papilloma. SYMPTOMATOLOGY
As the cercariae pierce the skin the patient feels irritation and itching at the involved site. The incubation period of the disease is thought to be 4-8 weeks. The early signs and symptoms are very indefinite, prolonged pyrexia with urticaria being described by many authors. The most outstanding symptom is haematuria. Blood in the urine as a sign of bilharziosis has been known and recognized for many centuries. It is mentioned in the Kahum papyrus of the XII dynasty (Patric and Griffith) and 400 years later in the Ebers papyrus. At a later stage of the disease the hematuria diminishes and symptoms referable to cystitis become much more predominant. Frequency of micturition is intense; urine is passed as many as 100 times during the day and night. The leucocyte count is also significant; usually an eosinophilia of 10 per cent27 per cent is found. X-ray studies of the genito-urinary tract in bilharziosis are helpful as an aid to diagnosis. Calcified ova when in sufficient concentration throw a shadow on the film producing characteristic shadows which are described under such headings as "the cloudy bladder of bilharziosis," "calcified lines and patches of bilharziosis." Calculi are present in a large number of cases of bilharziosis of the genito-urinary tract. They are usually formed in the later stages of the disease and throw the usual shadows on an x-ray film. TREATMENT
Bilharziosis is usually treated by intravenous injections of tartar emetic. This form of therapy was introduced by Christopherson in 1917-18. It has been stressed by Christopherson that the above drug should be given in effective dosage. The clinical results can be gauged by the determination of the presence or absence of the ova in the faeces and urine. The bilharzia parasite seldom resists a complete course of 30 grains given over a period of 4 to 5 weeks. Although the drug is highly toxic, Christopherson in 1927 reports only 7 fatal cases
442
H. R. NEWMAN
among 284,934 cases treated. During the course of treatment patients often complain of dry cough, pain in the chest and discomfort in the throat. A feeling of nausea and severe muscular pains may follow immediately an intravenous injection. Although the general treatment of bilharziosis with intravenous tartar emetic is essential, surgical intervention may be both very important and beneficial in selected cases. In the past, surgical intervention played only a palliative role in the later and final stages of the disease. Lithotomies, vesical, ureteric or renal, were performed, and, in the final stages, the bladder was drained through a perinea! incision in an attempt to alleviate, during the last few months of existence, the intolerable suffering caused by a grossly contracted bladder. After an intravenous injection of tartar emetic the pathological changes in the submucous tissue usually disappear, although, in many cases the lesions remain unaltered. These cases are very often aided by surgical intervention. Dr. Ibrahim Fahny El Minyawy of Cairo, has excised rectal papillomata with gratifying results. It seems rational and feasible to excise early vesical papillomata by means of a resectoscope. Such a procedure might prevent many of the complications such as malignant change, necrosis and infection, continued haemorrhages, etc. CASE REPORT
A male patient, aged 25, came to the out-patient department of All Saints' Hospital complaining of painless intermittent hematuria for the past 11 years. The hematuria which was characterized by the passage of fresh blood occurred as a rule at the end of micturition. There was no history of urinary frequency. This patient had migrated to England from Newcastle, South Africa, and had lived here during the past 5 years. Physical examination revealed nothing of note. The kidneys were not palpable and no tenderness was present. On rectal examination the prostate gland was normal in size and consistency. External genitalia were normal. The chest was normal. The cardio-vascular system was normal. The blood pressure was 130/80. Laboratory Examination: Urine: Alkaline reaction, specific gravity 1013, no albumin or sugar. Centrifuged specimen of urine revealed the presence of amorphous phosphates, 15~20 white blood cells, 5~6 red blood cells per high power field, and ova of schistosoma haemotobium. Culture of the urine was sterile after incubation of 24 hours on routine media. Blood urea: 30 mg. per 100 cc, blood urea concentration 3.0 per cent, 3.0 per cent, 2.8 per cent. X-ray of the abdomen was negative. Cystoscopic examination revealed lesions characteristic of bilharziosis. The bladder capacity was normal, amounting to 12 ounces of fluid. The ureteric orifices were normal. Scattered over the surface of the trigone and to a lesser extent over the vault were whitish, oval and rounded bodies. They were surrounded by areas of congestion. Some of the bodies were arranged in groups and more predominant in the region of the ureteric orifices. These small lesions
SURGERY AND BLADDER BILHARZIOSIS
443
simulated tubercles, but were very glossy in appearance. Immediately above and to the right of the right ureteric orifice a papilloma was located, its base fairly broad and its surface very bright red in colour simulating granulation tissue. The treatment may be summarized under 2 headings: (1) Local treatment, which consists of endoscopic resection of the papilloma; (2) general treatment, which consists of intravenous injections of sodium antimony tartrate. Endoscopic resection of the papilloma was carried out as follows: A low spinal anaesthetic was given using ¾cc stovaine. The anterior urethra was well lubricated by injecting into it very gently 5 cc glycerine, using a Canny Ryall syringe. It was then gradually dilated with steel sounds after which the resectoscope was introduced. Resection was carried out as in operation for prostate obstruction.
Fm. 1. X 195. Granulation tissue from base of bilharzial papilloma of bladder removed endoscopically. In addition to granulation tissue, there is an ovum seen in transverse section, and in this limiting membrane can easily be seen.
The resectoscope used was Millin's modification of the Canny Ryall instrument. The instrument is particularly useful for the resection of growths situated in the posterior half of the bladder. At the conclusion of the operation the bladder was thoroughly irrigated with silver nitrate solution 1: 5000. A soft rubber catheter, No. 24 F., was tied in for 48 hours. The patient made an uneventful recovery. The papilloma resected has been sectioned by Doctor Haler and illustrations are shown herewith (figs. 1, 2, 3). The general treatment consisted of intravenous injections of sodium antimony tartrate. The initial dose given was ½gr., and in each succeeding day the dose was gradually increased by ½gr. until a maximum dose of 2 grains was given daily. On the fourth day of treatment the patient complained of blurring vision and general weakness and remained in bed. On the fifth day of treatment he
444
H. R. NEWMAN
complained of muscular pain confined to the muscles of the neck. No injection was given on the sixth day but the symptoms persisted. On the seventh day the injections were resumed and 1 tablet of vitamin B 1 given 3 times daily (1
FIG. 2. X660. Demonstrating disintegrating ovum, showing pyknosis of nucleus and (?) early calcification of spinous area of ovum.
Frn. 3. X660. Showing active, presumably viable, ovum, with well demonstrated terminal spine and easily visible membrane covering, and so forth.
tablet is equivalent to 1 mg. aneurin 500 international units) (Roche Benerva vitamin B 1). The intravenous injections of 2 grains daily were continued until 27 gr. of sodium antimony tartrate had been given.
SURGERY AND BLADDER BILHARZIOSIS
445
After this patient was placed on vitamin B 1, the toxic symptoms disappeared; he felt well and was able to walk about without any ill effects. Urinalysis at the end of the treatment revealed reaction alkaline, specific gravity 1027, no albumin. No bilharzia! ova were seen. Cystoscopic examination revealed no evidence of a papilloma. There was slight congestion of the trigone. The bladder was practically normal. The patient was discharged with no urinary symptoms. SUMMARY
Bilharziosis of the bladder is a very uncommon disease in England. Schistosoma haemotobium is the commonest causative agent. The pathological lesion consists of a diffuse infiltration of the submucous layer or the formation of papillomata. The papillomata are usually situated in the regions of the ureteric orifices. The earliest symptom is usually intermittent painless hematuria, marked urinary frequency being a very late symptom. Sodium antimony tartrate given intravenously and endoscopic resection of papillomatas in selected cases is the treatment of choice. The value of vitamin B 1 in the control of neuro-muscular symptoms. arising during the administration of sodium antimony tartrate is illustrated in the case described above. I am indebted to Sir William De C. Wheeler for permission to publish this case, and to Dr. D. Haler for his kindness in preparing the slides, and in supplying the microphotographs and their description. REFERENCES BEER, EDWIN: Tumors of the Bladder. Baltimore: Williams & Wilkins Co., 1935. CHRISTOPHERSON, J.B., AND vVARD, R. OGIER: Brit. J. Surg., April, 1934. DIAMANTJS, A.: J. d'urol., Juillet, 1935. IBRABIM. ALY BEY: Congres Internationale de Medicine Tropicale, et d'Hygiene, 1932, n. 4!:19.
MAnnEN. FRANK CoLE: Congres Internationale de Medicine Tropicale, et d'Hygiene, 1932, p. 487. MILLIN. TERENCE: Brit. J. Surg., April, 1937, 25: 245. M TNYAWY, EL IBRAHIM F ARMY: Congres Internationale de ;\1.edicine Tropicale et d'Hygione, 1932, p. 547. RllIYRNIOTIS, P. C.: Congres Internationale de Medicine Tropicale et d'Hygiene, 1932, p. 499. SoROUR, M. F.: Congres Internationale de Medicine Tropicale et d'Hygiene, 1932, p. 321. Young's Practice of Urology. Philadelphia: W. B. Saunders Co., 1926.