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New Water-Soluble Medium (Sinografin) for Hysterosalpingography
New Water-Soluble Medium (Sinografin) for Hysterosalpingography M. J. Whitelaw, M.D., and Earl B. Miller, M.D.
ALTHOUGH as early as 1869 it had been reported by Chassinat that one o£ his patients had injected fluid through the uterus and tubes into the peritoneal cavity, visualization of the female genital tract had to wait until1910 before Rindfleisch, using bismuth as a radiographic medium, demonstrated partial filling of the tubes. Douay is quoted as saying that in 1912, Le Lourier reported the use of a solution of colloidal silver. In 1913 Dimier, working under Pozzi in Paris, used a 10% solution of Collargol to visualize the uterus. Due to the demise of one of his patients with peritonitis, he never completed his series of cases. Because of the war his paper was not published for three years. In 1914, Cary first used Collargol to test tubal patency. A few months later, Rubin34 published his paper on the value of Collargol as a contrast medium to outline the uterus. Soon, however, this medium was abandoned, since it was demonstrated that by remaining inspissated within the lumen, it might cause obstruction in a previously normal tube. Furthermore, it caused marked peritoneal irritation. In rapid succession thorium nitrate,
From the Departments of Obstetrics and Gynecology, and Radiology, University of California School of Medicine, San Francisco, and the Department of Obstetrics & Gynecology, Santa Clara County Hospital, San Jose, Calif. Read at the Sixth Annual Meeting of The Pacific Coast Fertility Society, Palm Springs, California, November 7, 1957. Exhibited at the Fourteenth Annual Meeting of the American Society for the Study of Sterility, April, 1958. The study was made possible by a grant from the E. R. Squibb Company. We wish to thank Drs. T. Foster, W. Graham, and H. Darling for their invaluable help during this study. 227
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sodium iodide, sodium bromide, and bismuth paste were utilized. Due to their severe peritoneal reactions, as well as their poor radiographic qualities, they all proved to be unsatisfactory. Then there followed the period of iodized oil, as exemplified by Lipiodol, a chemical compound of poppyseed oil and 40% pure iodine. This had been originated by Lafay in 1902. At first it was used extensively by Sicard and Forestier, and by Heuser. Various other iodized oils have been tried, and recently reports of two modifications of Lipiodol have appeared. 1 • 2 • 41 Complete absorption within 60 days is claimed for these modifications, and because of their lowered viscosity they delineate uterine and tubal pathology more successfully. Although these preparations are stable, do they meet the tenets of an ideal radiographic medium as first expressed by Neustadter, i.e. ( 1) is the medium totally innocuous to the organism as well as to the reproductive tract? ( 2) does it possess that degree of resorbability which will enable it to disappear from the system rapidly and completely after it has accomplished its diagnostic purpose, and leave no residue? and ( 3) does it have the proper viscosity? .· As to the first tenet, iodized oil has, on numerous occasions, been forced into the venous sinuses and from there into the uterine and ovarian veins. Beclere, Breitlander, and Hinrichs, Meaker and Zacharin all have reported the accidental introduction of Lipiodol into the ovarian veins. There has been ample evidence of pulmonary emboli in humans, 16 • 20 • 30• 42 which in some cases has been fatal.U· 13 • 50 Wong, Wu, and Chien sacrificed rabbits which weighed one and one-half to two kilograms, by intravenous injection of one cc. of Lipiodol. Hartgraves was unable to obtain these results. It has been stated that under direct fluoroscopy, injection into the sinuses can be avoided. This is not true, for at the moment one sees evidence of invasion of the sinuses, the oil is already within the lumen. Evidence to demonstrate conclusively that iodized oils may elicit foreign body reactions has been accumulated. Ries found extensive adhesions between the peritoneum, omentum, uterus, and bladder, which on being freed revealed sterile, walled-off cysts. In the microscopic section of the tubes, a large number of giant cells was seen within the homogeneous greenish granular mass. Novak and Lash have both reported the production of a foreign body reaction produced by Lipiodol within the pelvis. It has been shown by the author45 • 46 and others35 that if strictures or adhesions should be present in or around the fallopian tubes, interference with normal peristalsis is marked. It is diminished or may be totally absent. Under such
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conditions, the oil that remains inspissated within the tubal lumen could close the tube effectively and permanently. As to the second tenet, we have all had ample x-ray evidence that iodized oil remains for months within the peritoneal cavity. Schultze of the Berlin Frauenklinik beautifully demonstrated this fact at laparotomies done as long as 60 days after salpingography. In every case of occluded tubes, oil still remained within the lumen. In other cases, he was able to find a residue of the contrast oil in the form of a fatty film on the posterior surface of the uterus. In seven cases, foreign body reactions were found on the posterior surface of the uterus, the broad ligament, and the lateral peritoneal waU. Rabbiner demonstrated the presence of Lipiodol within the pelvis as long as one year after injection. Those of us who have had the opportunity of doing a tuboplasty can attest to the deleterious action of any type of oil solution. It is summed up best by Rock, who probably has had more experience in this field than any other gynecologist. He states categorically that oil in any form makes plastic repair of clubbed tubes nearly impossible. 32 He concludes, therefore, that in the investigation of the infertile female, oily media are absolutely contraindicated in salpingography.33 Because of these reasons, constant search has been under way in an endeavor to meet Neustadter's desiderata. Diodrast and Hippuran were used, but because of their rapid elimination from the genital tract into the peritoneal cavity, pathologic lesions of the uterus were overlooked. It became evident that some compound would have to be added which would increase the viscosity of the crystalline iodine structure. N eustadter, et al. tried 50% glucose, while Titus 43 • 44 and his co-workers reported on Skiodan and gum acacia in a 25% concentration. Originally Rubin36 had suggested adding a 50% solution of Rayopake. Norment, Montgomery, and Long, Golberger, Marshak, and Whitelaw48 all reported excellent results. However, because the use of this caused pain, it was discarded. Since then, Medipake H and Salpix have been tried. Both cause some pain, and the latter is shown to have a definite foreign body reaction. 4 • 17 Besides this, it crystallizes rapidly in the syringe, and it is difficult to work with. Because the author, together with Rock, 32 Rubin and others, feels that there are definite contraindications to the use of any type of oil media in the study of infertility, added to the fact that there has been as yet little clear-cut evidence presented to demonstrate that a 24-hour film gives any additional data on the condition of the pelvis or of tubal patency, it was decided to investigate a water-soluble medium, Sinografi.n, that had been used in Europe under the names of Endografi.n and Biligrafi.n. It is a
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70% solution of the methyl glucamine salt of N,N adipyl his ( 3 amino 2,4,6 triiodobenzoic acid). MATERIAL This report is based on a study of 157 private and clinic patients, in which we used a 70% Sinografin for hysterosalpingography and cineradiography. For practical consideration, these patients have been divided into five categories: 1. 41 infertility patients who had 3 or more negative Rubin tests. 2. 36 infertility patients who had had 1 or 2 negative Rubin tests. 3. 46 infertility patients who had not had a Rubin test. 4. 26 patients with various type of abnormal vaginal bleeding. 5. 8 patients with other complaints. The contraindications were: a. Infections of the genital tract b. Pregnancy c. Postovulatory phase d. Very active bleeding
TECHNIC The patients are instructed to take a cathartic on the night previous to the examination, and an enema on the morning of the examination. A bimanual examination is done previously to determine the size and position of the uterus, as well as the condition of the external os. A bivalve speculum is introduced, the cervix exposed and cleansed with iodine and alcohol. Under adequate illumination the anterior lip of the cervix is grasped with a deep bite of a single tooth tenaculum just above the external os, and a Jarcho selfretaining rubber-tipped acorn cannula (to which is attached a 10-cc. Luerlock syringe filled with Sinografin* free of air bubbles) is passed one centimeter into the endocervix. If the os is patulous, a Colvin screw type cannula must be substituted. The speculum is then taken out of the vagina by removing the lower half first. The upper section is then slipped out and left resting on the cannula. In this manner, better anatomical relationships are maintained, plus the fact that there is far less discomfort to the patient. The patient is then placed in correct position for fluoroscopy or cineradiography. It is of paramount importance that enough traction be made against the external os so that the sinografin, which is of a very low viscosity, " We wish to thank Dr. M. Lund of E. R. Squibb & Sons for the generous supply of Sinografin.
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does not leak. When done under fluoroscopy, leakage can be detected immediately, since the uterus should fill at once after 1 to 3 cc. have been injected. Failure to partially or completely visualize the uterus calls for the reapplication of the cannula. The dye in all cases is injected under fluoroscopy. In comparison with other media, it will be noted that very little pressure is needed. Within one to four seconds after starting the injection, the uterus is outlined. If the tubes are patent, spill is then seen in another few seconds. Usually a spot film is taken at the moment the uterine cavity appears filled, and again when the spill is first noted. To clearly visualize the total length of the fallopian tubes the x-ray film should be taken while injecting the dye. If blockage is present, pressure is noted immediately, and under fluoroscopy or the image amplifier, endocervical ballooning can be visualized. Excessive pressure is to be avoided and has never been found to be necessary. Usually a maximum of 3 to 4 cc. of Sinografin are needed. A few patients may require up to or over 10 cc. RESULTS Of the 41 patients in Group 1 who had had 3 or more negative Rubin tests, bilateral patency was shown in 8, while unilateral patency was demonstrated in 3 patients. One of these latter subsequently showed 3 more negative Rubin tests. A repeat salpingogram again revealed patency in the
...
Fig. 1. Hysterosalpingogram taken after 6 negative Rubin tests demonstrating spill on the right 4 seconds after starting the injection.
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Fig. 2. Spot film taken 5 seconds after Fig. 1 showing clubbing of left tube and further spill.
one tube (Figs. 1-3). Substantiation of unilateral blockage in one of the other patients was made at surgery. In Group 2 there were 36 patients who had one or two negative Rubin tests. Of these, 23 showed bilateral patency (Figs. 4-11). One showed unilateral patency. In only 12 salpingograms were we able to verify the negative Rubin tests (Figs. 12-14). Group 3 consisted of 46 patients, none of whom had had a Rubin test previously. There was bilateral patency in 39, occlusion of one tube in 2, and bilateral block in the remaining 5 patients. The only evidence of reaction to the medium was that 13 patients complained of moderate cramping 6 to
Fig. 3.
Spot film taken about 7 seconds after Fig. 2 showing heavy spill.
5
4 Fig. 4. Spot film taken after 2 negative Rubin tests were done, beautifully demonstrating the fimbria of the left tube with spill from right taken 5 seconds after injection. Fig. 5. Spot film taken approximately 7 seconds later clearly showing spill.
Fig. 6.
Spot film taken approximately 10 seconds after Fig. 5 showing pelvic scattering.
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7
8 Fig. 7. Spot film on patient with 2 negative Rubin tests showing tubal peristalsis and spill on left within 5 seconds of start of injection. Fig. 8. Spot film taken 6 seconds later than Fig. 7.
10 hours after injection. Two had rather severe 12-hour delayed pain, which lasted for 18 hours with a rise in temperature to 99.4. One of these patients became pregnant the following month. Laparotomy in the other case, done 5 weeks after injection, gave no indication of peritoneal irritation. In all cases where patency was present, the dye entered the peritoneal cavity within seconds after the injection was begun, as noted on fluoroscopy and corroborated by spot films or cineradiography. In none of the 22 patients was there
..
9
10
Fig. 9. Spot film taken about 10 seconds later showing bilateral spill. Fig. 10. Patient who had had 2 negative Rubin tests, showing tubal filling within 3 seconds.
12
1
Fig. 11. Spot film taken 5 seconds after Fig. 10, demonstrating bilateral spill. Fig. 12. Patient who had had a negative Rubin test, showing isthmic occlusion on right and a hydrosalpinx on the left with an endocervicitis (flat plate).
Fig. 13.
X-ray taken 10 seconds after Fig. 12.
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Fig. 14. Oblique showing a small submucous in left cornu the hydrosalpinx and endocervicitis of same patient as in Figs. 12 and 13.
x-ray evidence of nonabsorption within four hours. No accidental introduction of the medium into the sinuses was noted in our series, but inasmuch as the medium had been used previously for intravenous injections,* toxic results should not be anticipated. In Group 4, which consisted of 26 cases of menorrhagia, uterograms were positive in 8 patients, 4 of whom had submucous fibroids. Two of these latter patients were treated by myomectomy, one by hysterectomy, and one refused surgery. Three had polyps, in one case, multiple; all polyps were removed by curettage. One patient had an adenomyosis with generalized uterine enlargement demonstrated by x-ray. In Group 5, the miscellaneous group comprising 8 cases, 4 had an endocervicitis, 1 had a bicornuate uterus. DISCUSSION It is clearly evident from the findings in the several thousand cases in which this medium has been used that it is superior to iodized oil. In the • Cholografin used for intravenous gallbladder visualization.
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I
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I
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I I
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study of tubal occlusions, it is well to realize that our main purpose is to be able to aid those patients who have a block to pregnancy. Sinografin is ideally suited for this type of localization study as absorption takes place within a relatively short period of time. If tuboplasty is indicated, one's chance of success is higher when a nonirritating, quick-absorbing medium is employed. Iodized oil does not meet this specification. With an oil medium it is a well-known fact that inability to observe spill from the tubes into the peritoneal cavity is not conclusive proof of tubal occlusion. Occasionally with an oily medium only one tube may visualize, and at a later date the other tube is shown to be patent. It has been amply demonstrated that with an oily medium, there may be times when difficulty in interpretation of x-ray films occurs. These difficulties and disadvantages are not present with the use of Sinografin; with little pressure and within seconds, the medium clearly passes through the patent tube or tubes into the peritoneal cavity. Because of its low viscosity, there have been no false negative results noted in this series. Sinografin has given better delineation of both normal and abnormal tubal, uterine, and cervical conditions than any other medium that we have had the opportunity to use. The one objection that has been raised has been the occurrence of delayed pain which has followed in roughly 8 per cent of the patients. We have now been able to modify the original formula (this modification now consists of a mixture of 40% diotrizoate methyl glucamine and 20% iodipamide methyl glucamine) so as to obviate this difficulty for all practical purposes while retaining Sinografin's excellent contrast qualities, rapid absorption, and low viscosity. The findings in this study will be reported shortly. 49
CONCLUSIONS 1. Sinografin, a 70% solution of Cholografin, was used in 157 private and clinic patients for hysterosalpingography and cineradiography. It has given no false negative results and has demonstrated bilateral patency in 8 patients who had had 3 or more previously negative Rubin tests. 2. It has given excellent radiographic evidence of cervical, uterine, and tubal pathology and, in a number of cases, has clearly outlined the tubal ostia and also the mucosal pattern. 3. Under conventional fluoroscopy (or the image amplifier), peritoneal spill can be noted in every case where patency is present within seconds
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after starting the injection, thus eliminating the necessity for a 24-hour film. Sinografin is completely absorbed in 3 to 4 hours. 4. In 8 per cent of patients, it has caused delayed cramping, with 2 patients showing mild hyperpyrexia. (Modification of the formula appears to have obviated this. This modification now consists of a mixture of 40% diotrizoate methyl glucamine and 20% iodipamide methyl glucamine). 5. Sinografin would seem to offer a better opportunity for the success of tuboplastic procedures than oil solutions. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.
ARCOMANO, J.P., and BARNET, J. C. Fertil. & Steril. 9:222, 1958. BECKER, S. ]. Am. M. Women's A. 12:332, 1957. BECLERE, C. Bull. Sec. D'Obst. et de Gynec. 22:31, 1933. BERGMAN, F., et al. Acta radiol. 43:17, 1955. BREITLANDER, K., and HINRICHS, A. Zentralbl. Gynak. 65:124, 1941. CARY, H. Am.]. Obst. 69:462, 1914. CHASSINAT, R. Mem. et comp. rend. Soc. d. sc. med. de Lyon 2:84, 1869. CoLVIN, E. D. Am.]. Obst. & Gynec. 37:168, 1939. DARTIGUES and DIMmR. Paris chirug. 8:400, 1916. DouAY, E. Gynec. et Obst. 16:126, 1927. GAJAGO, E. Zentralbl. Gynak. 55:543, 1931. GoLDBERGER, M.A. ]. Mt. Sinai Hosp. New York 10:241, 1943. HANON, T. R. Personal communication. HARTGRAVEs, T. A. Am. ]. Roentgenol. 46:360, 1941. HEUSER, C. Bull. et mem. Soc. de Radiol. med de France, 1925. INGERSOLL, F. M., and RoBBINS, L. L. Am. ]. Obst. & Gynec. 53:307, 1947. KANTOR, H. 1., KAMHOLZ, J. H., and SMITH, A. L. Obst. & Gynec. 7:171, 1956. LAsH, A. F. Surg. Gynec. & Obst. 51:55, 1930. LAFAY, L. (serie hebdomadaire, vol. 1) 540-551, 602-614, 804-915, 1903. LIN, Y. Y., and Tsou, S. H. Chinese M. ]. 49:1241, 1935. MARSHAK, R. H. New YorkS.]. Med. 46:317, 1946. MEAKER, S. R. Am.]. Obst. & Gynec. 28:564, 1924. MoNTGOMERY, J. B., and LANG, W. Am. ]. Obst. & Gynec. 51:702, Nat. 1845. NEUSTADTER, T., EHRLICH, D. E., DuBOIS, J. C., and BLALOCK, G. R. Radiology 21:568, 1933. NoRMENT, W. B. Am. ]. Obst. & Gynec. 49:253, 1945. NovAK, J. Zentralbl. Gynak. 55:1449, 1931. RABBINER, B. Am.]. Obst. & Gynec. 29:100, 1935. Rms, E. Am.]. Obst. & Gynec. 17:728, 1929. RINDFLEISCH, W. Berliner Klin. Wchnschr. 2:780, 1910. RoBLEE, M. A., and MooRE, S. South. M. ]. 38:89, 1945. RocK, J. Conference on Diagnoses in Sterility. Thomas, Springfield, 1946, p. 237. RoCK, J. Fertil. & Steril. 8:513, 1957. RocK, J. Personal communication. RUBIN, I. C. Zentralbl. Gynak. 38:658, 1914. RuBIN, I. C. Am. ]. Obst. & Gynec. 20:28, 1930. RUBIN, I. C. ]. Mt. Sinai Hosp. New York 7:479, 1941.
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37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52.
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RuBIN, I. C. Uterotubal Insufflation. Mosby. St. Louis, 1947, p. 363. RuBIN, I. C., MYLLER, E., and HARTMANN, C. G. Fertil. & Steril. 4:357, 1953. SCHULTZE, G. K. F. Arch. Gyniik. 144:573, 1931. SICARD, J. A., and FoRESTIER, J. Bull. et mem. Soc. med. d. hop. de Paris 46:463 1922. STEINBERG, W. Am.]. Obst. & Gynec. 75:144, 1958. TITus, P. Am.]. Obst. & Gynec. 53:1067, 1947. TITus, P., et al. Am.]. Obst. & Gynec. 33:164, 1937. TITUS, P., et al. Am.]. Obst. & Gynec. 36:889, 1938. WHITELAW, M. J. Am.]. Obst. & Gynec. 25:475, 1933. WmTELAW, M. J. Diss. Fred. Wilhelm. Un., Berlin, 1934. WHITELAW, M. J. Arizona Med. 5:25, 1948. WmTELAW, M. J. Arizona Med. 5:42, 1948. WmTELAW, M. J. To be presented at Third World Congress on Fertility and Sterility, Amsterdam, June, 1959. WILLIAMS, E. R. Brit.]. Radiol.l7:13, 1944. WoNG, A. I. H., Wu, C., and CHIEN, M. H. Chinese M. ]. 46:162, 1932. ZACHARIN, D. M. ]. Australia 2:449, 1933.
ALTHOUGH as early as 1869 it had been reported by Chassinat that one o£ his patients had injected fluid through the uterus and tubes into the peritoneal cavity, visualization of the female genital tract had to wait until1910 before Rindfleisch, using bismuth as a radiographic medium, demonstrated partial filling of the tubes. Douay is quoted as saying that in 1912, Le Lourier reported the use of a solution of colloidal silver. In 1913 Dimier, working under Pozzi in Paris, used a 10% solution of Collargol to visualize the uterus. Due to the demise of one of his patients with peritonitis, he never completed his series of cases. Because of the war his paper was not published for three years. In 1914, Cary first used Collargol to test tubal patency. A few months later, Rubin34 published his paper on the value of Collargol as a contrast medium to outline the uterus. Soon, however, this medium was abandoned, since it was demonstrated that by remaining inspissated within the lumen, it might cause obstruction in a previously normal tube. Furthermore, it caused marked peritoneal irritation. In rapid succession thorium nitrate,
From the Departments of Obstetrics and Gynecology, and Radiology, University of California School of Medicine, San Francisco, and the Department of Obstetrics & Gynecology, Santa Clara County Hospital, San Jose, Calif. Read at the Sixth Annual Meeting of The Pacific Coast Fertility Society, Palm Springs, California, November 7, 1957. Exhibited at the Fourteenth Annual Meeting of the American Society for the Study of Sterility, April, 1958. The study was made possible by a grant from the E. R. Squibb Company. We wish to thank Drs. T. Foster, W. Graham, and H. Darling for their invaluable help during this study. 227
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sodium iodide, sodium bromide, and bismuth paste were utilized. Due to their severe peritoneal reactions, as well as their poor radiographic qualities, they all proved to be unsatisfactory. Then there followed the period of iodized oil, as exemplified by Lipiodol, a chemical compound of poppyseed oil and 40% pure iodine. This had been originated by Lafay in 1902. At first it was used extensively by Sicard and Forestier, and by Heuser. Various other iodized oils have been tried, and recently reports of two modifications of Lipiodol have appeared. 1 • 2 • 41 Complete absorption within 60 days is claimed for these modifications, and because of their lowered viscosity they delineate uterine and tubal pathology more successfully. Although these preparations are stable, do they meet the tenets of an ideal radiographic medium as first expressed by Neustadter, i.e. ( 1) is the medium totally innocuous to the organism as well as to the reproductive tract? ( 2) does it possess that degree of resorbability which will enable it to disappear from the system rapidly and completely after it has accomplished its diagnostic purpose, and leave no residue? and ( 3) does it have the proper viscosity? .· As to the first tenet, iodized oil has, on numerous occasions, been forced into the venous sinuses and from there into the uterine and ovarian veins. Beclere, Breitlander, and Hinrichs, Meaker and Zacharin all have reported the accidental introduction of Lipiodol into the ovarian veins. There has been ample evidence of pulmonary emboli in humans, 16 • 20 • 30• 42 which in some cases has been fatal.U· 13 • 50 Wong, Wu, and Chien sacrificed rabbits which weighed one and one-half to two kilograms, by intravenous injection of one cc. of Lipiodol. Hartgraves was unable to obtain these results. It has been stated that under direct fluoroscopy, injection into the sinuses can be avoided. This is not true, for at the moment one sees evidence of invasion of the sinuses, the oil is already within the lumen. Evidence to demonstrate conclusively that iodized oils may elicit foreign body reactions has been accumulated. Ries found extensive adhesions between the peritoneum, omentum, uterus, and bladder, which on being freed revealed sterile, walled-off cysts. In the microscopic section of the tubes, a large number of giant cells was seen within the homogeneous greenish granular mass. Novak and Lash have both reported the production of a foreign body reaction produced by Lipiodol within the pelvis. It has been shown by the author45 • 46 and others35 that if strictures or adhesions should be present in or around the fallopian tubes, interference with normal peristalsis is marked. It is diminished or may be totally absent. Under such
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conditions, the oil that remains inspissated within the tubal lumen could close the tube effectively and permanently. As to the second tenet, we have all had ample x-ray evidence that iodized oil remains for months within the peritoneal cavity. Schultze of the Berlin Frauenklinik beautifully demonstrated this fact at laparotomies done as long as 60 days after salpingography. In every case of occluded tubes, oil still remained within the lumen. In other cases, he was able to find a residue of the contrast oil in the form of a fatty film on the posterior surface of the uterus. In seven cases, foreign body reactions were found on the posterior surface of the uterus, the broad ligament, and the lateral peritoneal waU. Rabbiner demonstrated the presence of Lipiodol within the pelvis as long as one year after injection. Those of us who have had the opportunity of doing a tuboplasty can attest to the deleterious action of any type of oil solution. It is summed up best by Rock, who probably has had more experience in this field than any other gynecologist. He states categorically that oil in any form makes plastic repair of clubbed tubes nearly impossible. 32 He concludes, therefore, that in the investigation of the infertile female, oily media are absolutely contraindicated in salpingography.33 Because of these reasons, constant search has been under way in an endeavor to meet Neustadter's desiderata. Diodrast and Hippuran were used, but because of their rapid elimination from the genital tract into the peritoneal cavity, pathologic lesions of the uterus were overlooked. It became evident that some compound would have to be added which would increase the viscosity of the crystalline iodine structure. N eustadter, et al. tried 50% glucose, while Titus 43 • 44 and his co-workers reported on Skiodan and gum acacia in a 25% concentration. Originally Rubin36 had suggested adding a 50% solution of Rayopake. Norment, Montgomery, and Long, Golberger, Marshak, and Whitelaw48 all reported excellent results. However, because the use of this caused pain, it was discarded. Since then, Medipake H and Salpix have been tried. Both cause some pain, and the latter is shown to have a definite foreign body reaction. 4 • 17 Besides this, it crystallizes rapidly in the syringe, and it is difficult to work with. Because the author, together with Rock, 32 Rubin and others, feels that there are definite contraindications to the use of any type of oil media in the study of infertility, added to the fact that there has been as yet little clear-cut evidence presented to demonstrate that a 24-hour film gives any additional data on the condition of the pelvis or of tubal patency, it was decided to investigate a water-soluble medium, Sinografi.n, that had been used in Europe under the names of Endografi.n and Biligrafi.n. It is a
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70% solution of the methyl glucamine salt of N,N adipyl his ( 3 amino 2,4,6 triiodobenzoic acid). MATERIAL This report is based on a study of 157 private and clinic patients, in which we used a 70% Sinografin for hysterosalpingography and cineradiography. For practical consideration, these patients have been divided into five categories: 1. 41 infertility patients who had 3 or more negative Rubin tests. 2. 36 infertility patients who had had 1 or 2 negative Rubin tests. 3. 46 infertility patients who had not had a Rubin test. 4. 26 patients with various type of abnormal vaginal bleeding. 5. 8 patients with other complaints. The contraindications were: a. Infections of the genital tract b. Pregnancy c. Postovulatory phase d. Very active bleeding
TECHNIC The patients are instructed to take a cathartic on the night previous to the examination, and an enema on the morning of the examination. A bimanual examination is done previously to determine the size and position of the uterus, as well as the condition of the external os. A bivalve speculum is introduced, the cervix exposed and cleansed with iodine and alcohol. Under adequate illumination the anterior lip of the cervix is grasped with a deep bite of a single tooth tenaculum just above the external os, and a Jarcho selfretaining rubber-tipped acorn cannula (to which is attached a 10-cc. Luerlock syringe filled with Sinografin* free of air bubbles) is passed one centimeter into the endocervix. If the os is patulous, a Colvin screw type cannula must be substituted. The speculum is then taken out of the vagina by removing the lower half first. The upper section is then slipped out and left resting on the cannula. In this manner, better anatomical relationships are maintained, plus the fact that there is far less discomfort to the patient. The patient is then placed in correct position for fluoroscopy or cineradiography. It is of paramount importance that enough traction be made against the external os so that the sinografin, which is of a very low viscosity, " We wish to thank Dr. M. Lund of E. R. Squibb & Sons for the generous supply of Sinografin.
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does not leak. When done under fluoroscopy, leakage can be detected immediately, since the uterus should fill at once after 1 to 3 cc. have been injected. Failure to partially or completely visualize the uterus calls for the reapplication of the cannula. The dye in all cases is injected under fluoroscopy. In comparison with other media, it will be noted that very little pressure is needed. Within one to four seconds after starting the injection, the uterus is outlined. If the tubes are patent, spill is then seen in another few seconds. Usually a spot film is taken at the moment the uterine cavity appears filled, and again when the spill is first noted. To clearly visualize the total length of the fallopian tubes the x-ray film should be taken while injecting the dye. If blockage is present, pressure is noted immediately, and under fluoroscopy or the image amplifier, endocervical ballooning can be visualized. Excessive pressure is to be avoided and has never been found to be necessary. Usually a maximum of 3 to 4 cc. of Sinografin are needed. A few patients may require up to or over 10 cc. RESULTS Of the 41 patients in Group 1 who had had 3 or more negative Rubin tests, bilateral patency was shown in 8, while unilateral patency was demonstrated in 3 patients. One of these latter subsequently showed 3 more negative Rubin tests. A repeat salpingogram again revealed patency in the
...
Fig. 1. Hysterosalpingogram taken after 6 negative Rubin tests demonstrating spill on the right 4 seconds after starting the injection.
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Fig. 2. Spot film taken 5 seconds after Fig. 1 showing clubbing of left tube and further spill.
one tube (Figs. 1-3). Substantiation of unilateral blockage in one of the other patients was made at surgery. In Group 2 there were 36 patients who had one or two negative Rubin tests. Of these, 23 showed bilateral patency (Figs. 4-11). One showed unilateral patency. In only 12 salpingograms were we able to verify the negative Rubin tests (Figs. 12-14). Group 3 consisted of 46 patients, none of whom had had a Rubin test previously. There was bilateral patency in 39, occlusion of one tube in 2, and bilateral block in the remaining 5 patients. The only evidence of reaction to the medium was that 13 patients complained of moderate cramping 6 to
Fig. 3.
Spot film taken about 7 seconds after Fig. 2 showing heavy spill.
5
4 Fig. 4. Spot film taken after 2 negative Rubin tests were done, beautifully demonstrating the fimbria of the left tube with spill from right taken 5 seconds after injection. Fig. 5. Spot film taken approximately 7 seconds later clearly showing spill.
Fig. 6.
Spot film taken approximately 10 seconds after Fig. 5 showing pelvic scattering.
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7
8 Fig. 7. Spot film on patient with 2 negative Rubin tests showing tubal peristalsis and spill on left within 5 seconds of start of injection. Fig. 8. Spot film taken 6 seconds later than Fig. 7.
10 hours after injection. Two had rather severe 12-hour delayed pain, which lasted for 18 hours with a rise in temperature to 99.4. One of these patients became pregnant the following month. Laparotomy in the other case, done 5 weeks after injection, gave no indication of peritoneal irritation. In all cases where patency was present, the dye entered the peritoneal cavity within seconds after the injection was begun, as noted on fluoroscopy and corroborated by spot films or cineradiography. In none of the 22 patients was there
..
9
10
Fig. 9. Spot film taken about 10 seconds later showing bilateral spill. Fig. 10. Patient who had had 2 negative Rubin tests, showing tubal filling within 3 seconds.
12
1
Fig. 11. Spot film taken 5 seconds after Fig. 10, demonstrating bilateral spill. Fig. 12. Patient who had had a negative Rubin test, showing isthmic occlusion on right and a hydrosalpinx on the left with an endocervicitis (flat plate).
Fig. 13.
X-ray taken 10 seconds after Fig. 12.
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Fig. 14. Oblique showing a small submucous in left cornu the hydrosalpinx and endocervicitis of same patient as in Figs. 12 and 13.
x-ray evidence of nonabsorption within four hours. No accidental introduction of the medium into the sinuses was noted in our series, but inasmuch as the medium had been used previously for intravenous injections,* toxic results should not be anticipated. In Group 4, which consisted of 26 cases of menorrhagia, uterograms were positive in 8 patients, 4 of whom had submucous fibroids. Two of these latter patients were treated by myomectomy, one by hysterectomy, and one refused surgery. Three had polyps, in one case, multiple; all polyps were removed by curettage. One patient had an adenomyosis with generalized uterine enlargement demonstrated by x-ray. In Group 5, the miscellaneous group comprising 8 cases, 4 had an endocervicitis, 1 had a bicornuate uterus. DISCUSSION It is clearly evident from the findings in the several thousand cases in which this medium has been used that it is superior to iodized oil. In the • Cholografin used for intravenous gallbladder visualization.
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study of tubal occlusions, it is well to realize that our main purpose is to be able to aid those patients who have a block to pregnancy. Sinografin is ideally suited for this type of localization study as absorption takes place within a relatively short period of time. If tuboplasty is indicated, one's chance of success is higher when a nonirritating, quick-absorbing medium is employed. Iodized oil does not meet this specification. With an oil medium it is a well-known fact that inability to observe spill from the tubes into the peritoneal cavity is not conclusive proof of tubal occlusion. Occasionally with an oily medium only one tube may visualize, and at a later date the other tube is shown to be patent. It has been amply demonstrated that with an oily medium, there may be times when difficulty in interpretation of x-ray films occurs. These difficulties and disadvantages are not present with the use of Sinografin; with little pressure and within seconds, the medium clearly passes through the patent tube or tubes into the peritoneal cavity. Because of its low viscosity, there have been no false negative results noted in this series. Sinografin has given better delineation of both normal and abnormal tubal, uterine, and cervical conditions than any other medium that we have had the opportunity to use. The one objection that has been raised has been the occurrence of delayed pain which has followed in roughly 8 per cent of the patients. We have now been able to modify the original formula (this modification now consists of a mixture of 40% diotrizoate methyl glucamine and 20% iodipamide methyl glucamine) so as to obviate this difficulty for all practical purposes while retaining Sinografin's excellent contrast qualities, rapid absorption, and low viscosity. The findings in this study will be reported shortly. 49
CONCLUSIONS 1. Sinografin, a 70% solution of Cholografin, was used in 157 private and clinic patients for hysterosalpingography and cineradiography. It has given no false negative results and has demonstrated bilateral patency in 8 patients who had had 3 or more previously negative Rubin tests. 2. It has given excellent radiographic evidence of cervical, uterine, and tubal pathology and, in a number of cases, has clearly outlined the tubal ostia and also the mucosal pattern. 3. Under conventional fluoroscopy (or the image amplifier), peritoneal spill can be noted in every case where patency is present within seconds
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after starting the injection, thus eliminating the necessity for a 24-hour film. Sinografin is completely absorbed in 3 to 4 hours. 4. In 8 per cent of patients, it has caused delayed cramping, with 2 patients showing mild hyperpyrexia. (Modification of the formula appears to have obviated this. This modification now consists of a mixture of 40% diotrizoate methyl glucamine and 20% iodipamide methyl glucamine). 5. Sinografin would seem to offer a better opportunity for the success of tuboplastic procedures than oil solutions. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.
ARCOMANO, J.P., and BARNET, J. C. Fertil. & Steril. 9:222, 1958. BECKER, S. ]. Am. M. Women's A. 12:332, 1957. BECLERE, C. Bull. Sec. D'Obst. et de Gynec. 22:31, 1933. BERGMAN, F., et al. Acta radiol. 43:17, 1955. BREITLANDER, K., and HINRICHS, A. Zentralbl. Gynak. 65:124, 1941. CARY, H. Am.]. Obst. 69:462, 1914. CHASSINAT, R. Mem. et comp. rend. Soc. d. sc. med. de Lyon 2:84, 1869. CoLVIN, E. D. Am.]. Obst. & Gynec. 37:168, 1939. DARTIGUES and DIMmR. Paris chirug. 8:400, 1916. DouAY, E. Gynec. et Obst. 16:126, 1927. GAJAGO, E. Zentralbl. Gynak. 55:543, 1931. GoLDBERGER, M.A. ]. Mt. Sinai Hosp. New York 10:241, 1943. HANON, T. R. Personal communication. HARTGRAVEs, T. A. Am. ]. Roentgenol. 46:360, 1941. HEUSER, C. Bull. et mem. Soc. de Radiol. med de France, 1925. INGERSOLL, F. M., and RoBBINS, L. L. Am. ]. Obst. & Gynec. 53:307, 1947. KANTOR, H. 1., KAMHOLZ, J. H., and SMITH, A. L. Obst. & Gynec. 7:171, 1956. LAsH, A. F. Surg. Gynec. & Obst. 51:55, 1930. LAFAY, L. (serie hebdomadaire, vol. 1) 540-551, 602-614, 804-915, 1903. LIN, Y. Y., and Tsou, S. H. Chinese M. ]. 49:1241, 1935. MARSHAK, R. H. New YorkS.]. Med. 46:317, 1946. MEAKER, S. R. Am.]. Obst. & Gynec. 28:564, 1924. MoNTGOMERY, J. B., and LANG, W. Am. ]. Obst. & Gynec. 51:702, Nat. 1845. NEUSTADTER, T., EHRLICH, D. E., DuBOIS, J. C., and BLALOCK, G. R. Radiology 21:568, 1933. NoRMENT, W. B. Am. ]. Obst. & Gynec. 49:253, 1945. NovAK, J. Zentralbl. Gynak. 55:1449, 1931. RABBINER, B. Am.]. Obst. & Gynec. 29:100, 1935. Rms, E. Am.]. Obst. & Gynec. 17:728, 1929. RINDFLEISCH, W. Berliner Klin. Wchnschr. 2:780, 1910. RoBLEE, M. A., and MooRE, S. South. M. ]. 38:89, 1945. RocK, J. Conference on Diagnoses in Sterility. Thomas, Springfield, 1946, p. 237. RoCK, J. Fertil. & Steril. 8:513, 1957. RocK, J. Personal communication. RUBIN, I. C. Zentralbl. Gynak. 38:658, 1914. RuBIN, I. C. Am. ]. Obst. & Gynec. 20:28, 1930. RUBIN, I. C. ]. Mt. Sinai Hosp. New York 7:479, 1941.
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37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52.
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RuBIN, I. C. Uterotubal Insufflation. Mosby. St. Louis, 1947, p. 363. RuBIN, I. C., MYLLER, E., and HARTMANN, C. G. Fertil. & Steril. 4:357, 1953. SCHULTZE, G. K. F. Arch. Gyniik. 144:573, 1931. SICARD, J. A., and FoRESTIER, J. Bull. et mem. Soc. med. d. hop. de Paris 46:463 1922. STEINBERG, W. Am.]. Obst. & Gynec. 75:144, 1958. TITus, P. Am.]. Obst. & Gynec. 53:1067, 1947. TITus, P., et al. Am.]. Obst. & Gynec. 33:164, 1937. TITUS, P., et al. Am.]. Obst. & Gynec. 36:889, 1938. WHITELAW, M. J. Am.]. Obst. & Gynec. 25:475, 1933. WmTELAW, M. J. Diss. Fred. Wilhelm. Un., Berlin, 1934. WHITELAW, M. J. Arizona Med. 5:25, 1948. WmTELAW, M. J. Arizona Med. 5:42, 1948. WmTELAW, M. J. To be presented at Third World Congress on Fertility and Sterility, Amsterdam, June, 1959. WILLIAMS, E. R. Brit.]. Radiol.l7:13, 1944. WoNG, A. I. H., Wu, C., and CHIEN, M. H. Chinese M. ]. 46:162, 1932. ZACHARIN, D. M. ]. Australia 2:449, 1933.