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Uptake of Radioactive Phosphorus in Surgical Wounds of Rabbits
U P T A K E O F R A D I O A C T I V E P H O S P H O R U S IN SURGICAL WOUNDS OF RABBITS DAVID
O.
SOLOMON,
JEROME A.
M.D.,
BENNETT
LEVINE,
GANS,
M.D.
AND
M.D.*
Cleveland, Ohio
The increased uptake of radioactive phosphorus ( P ) by certain tumors is the basis for a useful diagnostic test for intraocular neoplasms. However, this test has questionable value following ocular surgery, as stated by Carmichael and Leopold, Terner, Leopold and Eisenberg, and Solomon, Moses and Eigner. This clinical impression was confirmed experimentally by Solomon, Moses, and Eigner when they found increased uptake of P over the operated site following resection of a rectus muscle (the test was done on the third postoperative day in rabbits). Carmichael and Leopold stated that the uptake test is unreliable for six weeks after surgery, and Terner, Leopold, and Eisenberg suggested waiting eight weeks before using the uptake test, but there is no evidence that the test becomes reliable after six or eight weeks. The purpose of this study was to learn something of the uptake characteristics of the healing surgical wound. 3 2
1
2
3
decade scaler. Counts were taken over the operated site (right superior rectus muscle insertion), and the left superior rectus muscle insertion. The percentage of uptake of P by the surgical wound is calculated by comparing the radioactive counts over the operated site to the counts over the same area of the other eye (left superior rectus muscle) : S2
Counts R.S.R. — Counts L.S.R. X 100
3
Counts L.S.R.
32
1
The uptake test is considered positive when the counts over the lesion (the surgical wound) are at least 30% more than the counts over the control area. RESULTS
2
MATERIAL
A N D METHODS
Rabbits weighing about 3 kg were selected. Under general anesthesia, the right superior rectus muscle was isolated, excised from its insertion, then resutured to its insertion with 4-0 plain catgut suture. The radioactive phosophorus uptake test was done on groups of rabbits two weeks, three weeks, four weeks and six weeks after surgery. The uptake test was begun with an injection of 200 microcuries of P into an ear vein of each rabbit, followed by radioactive counting, after 72 hours, with a miniature Geiger tube* attached to the standard S2
From the Department of Ophthalmology, Mount Sinai Hospital. •Steiner Radioisotope Laboratory, Mount Sinai Hospital of Cleveland. t Type 224, Anton Electronic Laboratories, Brooklyn, New York.
- - % uptake
Table 1 shows the individual results of this study. The group of rabbits injected with P two weeks after surgery actively incorporated the radioactive phosphorus in their surgical wounds as shown by an average uptake of 59% in that group. The second group tested three weeks after surgery incorporated the P less actively, with only six positive uptakes of the 16 rabbits tested, producing a group average of 22%. By the fourth postoperative week there was not a single positive uptake in the group of 22, and the average was 15.5%. The six-week group followed the trend toward decreasing uptake with a drop in the group average to 3% (fig.l). 32
32
DISCUSSION
In rabbits there is an abnormally high uptake of P by the surgical wound throughout three weeks of healing. During this period the wound acts like neoplastic tissue in its ability to concentrate radioactive phosphorus, and therefore produces a high number of false positives in this diagnostic procedure. 32
537
538
AMERICAN JOURNAL OF OPHTHALMOLOGY
S E P T E M B E R , 1968
TABLE 1 PERCENT UPTAKE OF **P OF SURGICAL WOUND
2 Weeks After Surgery
3 Weeks After Surgery
38* 49*
4 Weeks After Surgery
15 20 17 2 23 29 2 0 19 18 5 20 28 25 4 7 29 29
34* 40* 41* 49* 25 26 3 10 - 5 0 30* 22 15 5 27 33*
61*
29 106* 103* 43* 43* Mean 59%
6 Weeks After Surgery
Mean 22%
-12 "24 25 -is 5 - 9 - 9 -21 0 14 12 27 18 25 Mean 3%
— 11
12 13 18 Mean
15.5%
* Positive uptake. The uptake of radioactive phosphorus of the surgical wound is expressed as percent increase or decrease ( — ) , compared with the uptake of the same area (unoperated) of the other eye. 30% or greater is considered a positive uptake.
By the fourth postoperative week the uptake of the surgical wound decreases to an average 15.5% (no positives). The reliability of this test in the fourth postoperative week is
certainly questionable. By the sixth postoperative week, the average uptake of the surgical wound is 3%, approaching the normal range, thereby permitting use of this diagnostic procedure with a greater degree of reliability. The 72-hour count was used because of laboratory scheduling but it has been our experience, as well as that of Terner, Leopold, and Eisenberg, that tissues which show an increased uptake of P at 24 hours have an even higher relative uptake at 48 and 72 hours. The 24-hour count is used clinically because of a decrease in radioactive counts that occurs at 48 and 72 hours, making the test less reliable. The problem of decreased counts at 72 hours was eliminated in our study by using five times the usual clinical dose of P . 2
32
1
2
3
4
POST-OPERATIVE PERIOD
s
6
(WEEKS)
Fig. 1 (Solomon, Gans, and Levine) The uptake of radioactive phosphorus by the surgical wound is 59% above normal two weeks after surgery. The surgical wound decreases its uptake ability and approaches normal at the sixth postoperative week.
82
The findings of this study cannot be applied directly to human patients without further studies but these results have shown the ability of the surgical wound to incorporate
V O L . 66, N O . 3
U P T A K E OF RADIO/
P and, further, that this ability decreases with time. There is little question that the surgical wound in man also has the ability to concentrate P , but to what degree this is influenced by the type of surgery and the duration of the postoperative period remains to be determined. W e have begun a followup study to determine the postoperative period required in man for the surgical wound to return to normal and to determine whether this period might be influenced by the type of surgery and the degree of postoperative inflammatory reaction. 32
32
SUMMARY
The radioactive phosphorus test has questionable value following ocular surgery. The
SURGICAL RESULTS IN
539
healing surgical wound (of rabbits) behaves like neoplastic tissue in that it may give a positive test for malignancy up to four weeks after surgery when the radioactive phosphorus test is used. The surgical wound may continue to take up phosphorus at a rate higher than normal through the sixth postoperative week. REFERENCES
1. Carmîchael, P. L. and Leopold, I. H . The radioactive phosphorus test in ophthalmology. Am. J. Ophth. 49:484, 1960. 2. Temer, I. S., Leopold, I. H . and Eisenberg, I. J. The radioactive phosphorus P" uptake test in ophthalmology. Arch. Ophth. 55:52, 1956. 3. Solomon, O. D., Moses, L. and Eigner, E. H . Validity of the radioactive phosphorus uptake test following ocular surgery. Am. J. Ophth. 55:1237, 1963.
RUBELLA AND NONRUBELLA
CONGENITAL EDWARD
T I V E PHOSPHORUS
CATARACTS
COTLIER,
M.D.
St. Louis, Missouri
Since the rubella virus isolations from the lens and aqueous humor of patients with congenital rubella, ' questions have been raised as to whether a better differentiation could be made between rubella and other types of congenital cataract. For years it was believed that the clinical and surgical prognosis of rubella eyes was good. In a recent study, however, Scheie, Schaffer, Plotkin and Kertesz found that in 43% of eyes operated on for congenital rubella cataracts, severe postoperative complications led to the eventual loss of many eyes. These findings appear restricted to that rubella population, and are unusual in that relatively few congenital rubella eyes have been removed, despite the 1 2
3
4
From the Department of Ophthalmology and the Oscar Johnson Institute, Washington University Medical School. This study was supported by U S P H S Grant N B 07393, and a Career Development Award of the National Institute of Neurological Diseases and Blindness.
widespread epidemic of 1964-1965 in the United States. Furthermore, although many correctly diagnosed rubella congenital cataracts have been subjected to surgery during the last 25 years, no reports of poor results in such cases are available. In the series of eyes reported here, there was little or no difference in the results of surgery for rubella and nonrubella congenital cataracts. MATERIAL PATIENTS
AND METHODS
A N D SURGERY
The infants included in this study had cataract extractions by various surgeons at McMillan Hospital, Washington University School of Medicine, between 1960-1968. Eleven rubella syndromes were diagnosed on the basis of maternal history, deafness, cardiac or ocular defects, and/or rubella virus recovery from the lens, aqueous humor, or throat swab. Thirty-six randomly selected
O.
SOLOMON,
JEROME A.
M.D.,
BENNETT
LEVINE,
GANS,
M.D.
AND
M.D.*
Cleveland, Ohio
The increased uptake of radioactive phosphorus ( P ) by certain tumors is the basis for a useful diagnostic test for intraocular neoplasms. However, this test has questionable value following ocular surgery, as stated by Carmichael and Leopold, Terner, Leopold and Eisenberg, and Solomon, Moses and Eigner. This clinical impression was confirmed experimentally by Solomon, Moses, and Eigner when they found increased uptake of P over the operated site following resection of a rectus muscle (the test was done on the third postoperative day in rabbits). Carmichael and Leopold stated that the uptake test is unreliable for six weeks after surgery, and Terner, Leopold, and Eisenberg suggested waiting eight weeks before using the uptake test, but there is no evidence that the test becomes reliable after six or eight weeks. The purpose of this study was to learn something of the uptake characteristics of the healing surgical wound. 3 2
1
2
3
decade scaler. Counts were taken over the operated site (right superior rectus muscle insertion), and the left superior rectus muscle insertion. The percentage of uptake of P by the surgical wound is calculated by comparing the radioactive counts over the operated site to the counts over the same area of the other eye (left superior rectus muscle) : S2
Counts R.S.R. — Counts L.S.R. X 100
3
Counts L.S.R.
32
1
The uptake test is considered positive when the counts over the lesion (the surgical wound) are at least 30% more than the counts over the control area. RESULTS
2
MATERIAL
A N D METHODS
Rabbits weighing about 3 kg were selected. Under general anesthesia, the right superior rectus muscle was isolated, excised from its insertion, then resutured to its insertion with 4-0 plain catgut suture. The radioactive phosophorus uptake test was done on groups of rabbits two weeks, three weeks, four weeks and six weeks after surgery. The uptake test was begun with an injection of 200 microcuries of P into an ear vein of each rabbit, followed by radioactive counting, after 72 hours, with a miniature Geiger tube* attached to the standard S2
From the Department of Ophthalmology, Mount Sinai Hospital. •Steiner Radioisotope Laboratory, Mount Sinai Hospital of Cleveland. t Type 224, Anton Electronic Laboratories, Brooklyn, New York.
- - % uptake
Table 1 shows the individual results of this study. The group of rabbits injected with P two weeks after surgery actively incorporated the radioactive phosphorus in their surgical wounds as shown by an average uptake of 59% in that group. The second group tested three weeks after surgery incorporated the P less actively, with only six positive uptakes of the 16 rabbits tested, producing a group average of 22%. By the fourth postoperative week there was not a single positive uptake in the group of 22, and the average was 15.5%. The six-week group followed the trend toward decreasing uptake with a drop in the group average to 3% (fig.l). 32
32
DISCUSSION
In rabbits there is an abnormally high uptake of P by the surgical wound throughout three weeks of healing. During this period the wound acts like neoplastic tissue in its ability to concentrate radioactive phosphorus, and therefore produces a high number of false positives in this diagnostic procedure. 32
537
538
AMERICAN JOURNAL OF OPHTHALMOLOGY
S E P T E M B E R , 1968
TABLE 1 PERCENT UPTAKE OF **P OF SURGICAL WOUND
2 Weeks After Surgery
3 Weeks After Surgery
38* 49*
4 Weeks After Surgery
15 20 17 2 23 29 2 0 19 18 5 20 28 25 4 7 29 29
34* 40* 41* 49* 25 26 3 10 - 5 0 30* 22 15 5 27 33*
61*
29 106* 103* 43* 43* Mean 59%
6 Weeks After Surgery
Mean 22%
-12 "24 25 -is 5 - 9 - 9 -21 0 14 12 27 18 25 Mean 3%
— 11
12 13 18 Mean
15.5%
* Positive uptake. The uptake of radioactive phosphorus of the surgical wound is expressed as percent increase or decrease ( — ) , compared with the uptake of the same area (unoperated) of the other eye. 30% or greater is considered a positive uptake.
By the fourth postoperative week the uptake of the surgical wound decreases to an average 15.5% (no positives). The reliability of this test in the fourth postoperative week is
certainly questionable. By the sixth postoperative week, the average uptake of the surgical wound is 3%, approaching the normal range, thereby permitting use of this diagnostic procedure with a greater degree of reliability. The 72-hour count was used because of laboratory scheduling but it has been our experience, as well as that of Terner, Leopold, and Eisenberg, that tissues which show an increased uptake of P at 24 hours have an even higher relative uptake at 48 and 72 hours. The 24-hour count is used clinically because of a decrease in radioactive counts that occurs at 48 and 72 hours, making the test less reliable. The problem of decreased counts at 72 hours was eliminated in our study by using five times the usual clinical dose of P . 2
32
1
2
3
4
POST-OPERATIVE PERIOD
s
6
(WEEKS)
Fig. 1 (Solomon, Gans, and Levine) The uptake of radioactive phosphorus by the surgical wound is 59% above normal two weeks after surgery. The surgical wound decreases its uptake ability and approaches normal at the sixth postoperative week.
82
The findings of this study cannot be applied directly to human patients without further studies but these results have shown the ability of the surgical wound to incorporate
V O L . 66, N O . 3
U P T A K E OF RADIO/
P and, further, that this ability decreases with time. There is little question that the surgical wound in man also has the ability to concentrate P , but to what degree this is influenced by the type of surgery and the duration of the postoperative period remains to be determined. W e have begun a followup study to determine the postoperative period required in man for the surgical wound to return to normal and to determine whether this period might be influenced by the type of surgery and the degree of postoperative inflammatory reaction. 32
32
SUMMARY
The radioactive phosphorus test has questionable value following ocular surgery. The
SURGICAL RESULTS IN
539
healing surgical wound (of rabbits) behaves like neoplastic tissue in that it may give a positive test for malignancy up to four weeks after surgery when the radioactive phosphorus test is used. The surgical wound may continue to take up phosphorus at a rate higher than normal through the sixth postoperative week. REFERENCES
1. Carmîchael, P. L. and Leopold, I. H . The radioactive phosphorus test in ophthalmology. Am. J. Ophth. 49:484, 1960. 2. Temer, I. S., Leopold, I. H . and Eisenberg, I. J. The radioactive phosphorus P" uptake test in ophthalmology. Arch. Ophth. 55:52, 1956. 3. Solomon, O. D., Moses, L. and Eigner, E. H . Validity of the radioactive phosphorus uptake test following ocular surgery. Am. J. Ophth. 55:1237, 1963.
RUBELLA AND NONRUBELLA
CONGENITAL EDWARD
T I V E PHOSPHORUS
CATARACTS
COTLIER,
M.D.
St. Louis, Missouri
Since the rubella virus isolations from the lens and aqueous humor of patients with congenital rubella, ' questions have been raised as to whether a better differentiation could be made between rubella and other types of congenital cataract. For years it was believed that the clinical and surgical prognosis of rubella eyes was good. In a recent study, however, Scheie, Schaffer, Plotkin and Kertesz found that in 43% of eyes operated on for congenital rubella cataracts, severe postoperative complications led to the eventual loss of many eyes. These findings appear restricted to that rubella population, and are unusual in that relatively few congenital rubella eyes have been removed, despite the 1 2
3
4
From the Department of Ophthalmology and the Oscar Johnson Institute, Washington University Medical School. This study was supported by U S P H S Grant N B 07393, and a Career Development Award of the National Institute of Neurological Diseases and Blindness.
widespread epidemic of 1964-1965 in the United States. Furthermore, although many correctly diagnosed rubella congenital cataracts have been subjected to surgery during the last 25 years, no reports of poor results in such cases are available. In the series of eyes reported here, there was little or no difference in the results of surgery for rubella and nonrubella congenital cataracts. MATERIAL PATIENTS
AND METHODS
A N D SURGERY
The infants included in this study had cataract extractions by various surgeons at McMillan Hospital, Washington University School of Medicine, between 1960-1968. Eleven rubella syndromes were diagnosed on the basis of maternal history, deafness, cardiac or ocular defects, and/or rubella virus recovery from the lens, aqueous humor, or throat swab. Thirty-six randomly selected