A case of bilateral renal-cell carcinoma unsuccessfully treated with bench surgery is reported. The reason for failure was apparently the toxicity of the contrast media used during the ex vivo arteriographic studies. © 1973

Alfidi

Ausman

Belzer

Calne

Chaplin

D. Gallot

D.P. Stables

Hardy

J. Taubman

J.L. Corman

Knoefel

Kutt

M. Fiala

Merserau

O. Stonington

R. Girard

Rand

Starzl

T.E. Starzl

Zinner

English

PubMed

Corman, JL

Stonington, O

Giraard, R

Stables, DP

Fiala, M

Taubman, J

Gallot, D

Starzl, TE

Name not available

Arteriography during ex vivo renal perfusion: A complication

Crossref

Girard, R

D-Scholarship@Pitt

SCIENTIFIC ARTICLES ARTERIOGRAPHY DURING EX VIVO RENAL PERFUSION* A complication J. L. CORMAN, M.D. R. GIRARD, M.D. O. STONINGTON, M.D. D. P. STABLES, M.D. M. FIALA, M .D. J. TAUBMAN, M.D. D. GALLOT, M.D. T. E. STARZL, M.D. From the Departments of Surgery and Radiology, University of Colorado School of Medicine, and Veterans Administration Hospital, Denver, Colorado ABSTRACT -A case of bilateral renal-cell carcinoma unsuccessfully treated with bench surgery is reported. The reason for failure was apparently the toxicity of the contrast media used during the ex vivo arteriogmphic studies. In a recent publication we discussed the ad-vantages of a method of renal autotransplantation by which a kidney could be removed, perfused under hypothermia, studied angiographically, and have its structures dissected and repaired before finally revascularized heteropically as an autotransplant.l The possibility was discussed of applying the same techniques for special in-dications, such as malignant disease in a solitary kidney, advanced staghorn calcul us disease renal trauma, or lesions of the ureter, to mentio~ only four examples .2•3 A patient suffering from Lindau-von Hippel disease with carcinoma of both kidneys has since been surgically treated in attempts to partially resect first the right and then the left kidney by autotransplant. Both autografts were lost due to arterial thrombosis probably because of an unsuitable contrast medium used during ex vivo arteriographic studies. The case is re-ported here, with special emphasis on the choice of contrast medium under conditions of hypo-thermic ex vivo perfusion. *This work was supported by research grants from Veterans Administration; Grants RR-00051 and RR-00069 from general clinical research centers program of the Division of Research Resources, National Institutes of Health; and Gra nts AI-10176-01, AI-AM-08898 , and AM-07772. 222 Case Report In December, 1972, a forty-five-year-old man was proved by excretion urography and renal arteriography to have bilateral multicentric renal-cell carcinoma and simple cysts (Figs . 1 and 2). There was a family history of Lindau-von Hippel disease, with one brother currently under treat-ment for renal-cell carcinoma and 2 other siblings possibly having died of the disease. No metas-tases were detectable . Kidney function was normal, with a blood urea nitrogen level of 12 mg. and serum creatinine 1.1 mg. per 100 ml. The patient's right kidney was removed on February 23, 1973, through a flank incision with maximum length of the renal vessels and ureter.l ,4 The upper pole was expanded by both a large cyst and carcinoma which showed no sign of capsular invasion. The kidney was flushed with a cold, balanced electrolyte solution containing low molecular dextran and heparin (Perfudex) and connected to a Belzer-type kidney perfusion machine t by the two renal arteries (Fig. 3A). The perfusate consisted of cold (7°C.) de-flocculated homologous plasma. t Manufac tured by Waters Instrume nts , Inc., Roches ter, Minnesota. UROL OGY I SEPT EMBER 1973 I VOLUME II , NUMBER 3 FIGURE 1. Preoperative aorto-gram showing right kidney vascularized by 2 renal arteries, both supply upper- and lower-pole carcinomas (arrows). Left kidney also contains 2 carci-nomas (arrows). Both organs contain multiple small cysts. FIGURE 2. Preoperative selective arteriogram with injection of right large lower renal artery: (A) early arterial phase, (B) after epinephrine injection, and (C) nephrogram phase (lesions shown by arrows). The vascular anatomy of the extracorporeal kidney was then thoroughly studied with arterio-grams following the technique which has been described in a previous publication.! However, whereas the contrast medium used in the pre-vious reported cases had been 60% meglumine iothalamate (Conray-60), in this case 50% sodium UROLOGY I SEPTEMBER 1973 I VOLUME II , NUMBER 3 diatrizoate (Hypaque sodium 50%) was used (total 25 mI.). The kidney was flushed with the perfusate after every arteriogram, and the venous effiuent was discarded to avoid recycling of the contrast medium. The carcinoma in the upper pole was supplied by two segmental arteries, one arising from each of the two renal arteries, while 223 FIGURE 3. Right kidney (A) under hypothermic perfusion, both carcinomas and multiple cysts visible; (B) arteriogram during ex vivo perfusion showing double arterial supply and its relationship to tumors. two segmental arteries, both arising from the lowest of the two renal arteries , supplied the tumor in the lower pole (Fig. 3B). The branches supplying the upper-pole carci-noma were ligated and injected distally with methylene-blue dye. The upper pole was re-sected. The same procedure was followed in the lower pole (Fig. 4A). During this time the perfusion of the organ was intermittently inter-rupted to avoid excessive perfusate leakage through the cut parenchyma. T he perfusate leaks were controlled, and two major calices were 224 ligated. A fin al arteriogram with the same con-trast medi um confirmed the good vascularization and the absence of tumor in the remnant of the kidney (Fig. 4B). Gross examination of the resected poles showed that both carcinomas were well circumscribed, and that the resection had been carried out at a reasonable distance from them. The resected kidney tissue weighed 70 Gm. Histologic examination confirmed the diag-nosis of multicentric renal-cell carcinoma. The patient's flank incision was close d. H was placed in a supine position, and an ante rior lower abdominal incision was made on the left as is done in a kidney homotransplantation : ' T he renal vein anastomosis was pe rforme d end-to-side to the external iliac ve in. T he main trunk of the hypogastric artery was anas tomos d e nd-to-end to the large lower renal artery, and the smaller superior renal mtery was anastomosed to a segmental branch of the lower renal artery. The kidney remnant was revascularized after a cold ischemic time of five hours and seven minutes. The autograft turned pink, but afte r a few minutes became slightly bluish and soft. No explanation was found for this abnormality. The procedure was completed by a classical uretero-neocystostomy. Postoperatively, Mercury-197 renal scan per-fo rmed on the second postoperative day showed decreased isotope accumulation in the autograft. On the eighth day, there was no uptake at all. The kidney was removed and was found to be completely infarcted. The main arteries had a few organized thrombi, and the vein was com-pletely thrombosed with extension to the iliac as well as the femoral vein. No obvious surgical mistakes were discovered, but it was assumed that one had been committed. No residual carcinoma was identified. One month later, the same procedure was per-formed on the left kidney. At the end of the ex vivo dissection of the organ and removal of both poles, about 50 per cent of the original kidne¥ was left without residual renal-cell carcinoma. This was vascularized by a single renal artery. As with the other kidney, ex vivo arteriograms were performed with 50% sodium diatrizoate but in ad-dition, also with 66% meglumine and 10% sodi-um diatrizoate (Renografin 76) totaling 25 cc. The autograft was placed in the right iliac fossa, anastomosing the renal artery end-to-end to the hypogastric artery and renal vein end-to-side to the external iliac vein after six and one-half hours of cold ischemia. The phenomenon previously described occurred - the graft turned pink for a few minutes and then became bluish and soft. UROLOGY I SEPTEMBER 1973 I VOLUME II , NUMB ER 3 FIGURE 4. (A) Resected carcinomas after definition of vascularization by injection of methylene blue dye; remnant of one third of right kidney ready for autotransplantation. (B) Final arteriogram during ex vivo perfusion after resection of tumors. It was removed after a one-half-hour observation period during which intra-arterial injections of papaverin and procaine were attempted without success. The anastomoses were perfect, but there were widely distributed fresh clots in the secondary and tertiary arterial branches. Histologic examination of the specimen con-firmed the presence in the large arteries of aggregated fibrin, platelets, and erythrocytes with extensive thrombosis in the smaller arteries. There was no residual renal-cell carcinoma. The patient is now on chronic hemodialysis awaiting kidney transplantation. Comment In this case, there were no preoperative signs of extrarenal malignant disease. Para-aortic lymph nodes and perinephric fat removed during the surgical procedure were carefully examined and found to be free oftumor. Finally, no residual cancer was identified in both removed autografts. Consequently, the patient should have been a good candidate for the proposed partial kidney resection(s). After the first unsuccessful kidney autotrans-plantation in this patient, the loss of the organ was assumed to be due to some unrecognized technical mistake. However, the failure of the second autograft for similarly inexplicable reasons prompted special inquiries of both a prospective and retrospective nature. Slight hypocoagulability of intraoperative blood samples was found. No cold agglutinins were UROLOGY I SEPTEMBER 1973 I VOLUME II, NUMBER 3 detected in the serum. Results of skin tests with the three contrast media previously lIsed were negative. The perfusate used was homologous de floc-culated plasma processed in exactly the same way as in the past.5 The blood type of the plasma donor and the patient were the same. The per-fusion had been carried out at 7° to 10°C. as is done routinely in kidney preservation for trans-plantation purposes. The ischemia time was shorter than in most of our preserved cadaveric kidney transplants It was suspected that the contrast medium could have been responsible. In this case, in-stead of using 60% meglumine iothalamate,l 50% sodium diatrizoate, and 66% meglumine and 10% sodium diatrizoate were administered. All of these contrast media are used regularly for various forms of arteriography in vivo. They are all triiodinated derivatives of benzoic acid, prepared in hyperosmolar solution. This hyper-osmolarity is responsible for much of the toxicity of these drugs.6 In vivo and in vitro, at high con-centrations, they produce crenation of red cells, hemolysis, and red-cell agglutination.7' 9 Coagula-tion factors are disturbed by an increase in thrombin time, interference with polymerization of the fibrin monomers, and decrease in factor V. 8•9 They are known to damage the vascular endothelium 10.12 and, if crenation of red cells occurs, the vascular resistance may increase. 13 Many of these toxic effects seem to be less prom-inent with the preparations which contain the meglumine cation instead of sodium.6 In the 225 present context, the most important difference is that, according to the manufacturer's literature, 50% sodium diatrizoate and meglumine sodium diatrizoate crystallize or precipitate at low temperatures, while meglumine iothalamate is stable even below O°C. The repeated injections of 50% sodium diatrizoate and meglumine and sodium diatri-zoate at low temperatures were suspected to be the cause of autograft losses. Since 60% meglumine iothalamate had been used success-fully in past cases under otherwise similar con-ditions, the gravest doubts were only about sodium diatrizoate and were entertained about meglumine and sodium diab·izoate. 1 To test the toxicity hypothesis , 12 mongrel dogs' kidneys were autotransplanted after being cooled to 4 ° C. by the infusion of chilled lactated Ringer's solution. Then 50% sodium diatrizoate, meglumine and sodium diatrizoate, and meglu-mine iothalamate were injected intra-arterially in doses of 20 to 30 m!. With all 3 contrast media, the kidneys turned bluish and remained soft after revascularization if they were not washed after the injection . This finding was less striking for the organs treated with 60% meglumine iothalamate. None of the dogs receiving kidneys so treated were able to survive. On the other hand, if the kidneys were care-fully washed with lactate Ringer's solution im-mediately after injection of the contrast medium, as suggested by Alfidi and Magnusson,14 the organs were temporarily cyanotic after auto-transplantation, but they were able to sustain the animal's life after revascularization. Again, the best results were obtained with 60% meglu-mine iothalamate in that the transient cyanosis was both less intense and of shorter duration . From these studies, it was concluded that the choice of contrast medium for ex vivo renal 226 arteriography under conditions of hypothermia is critical, and that the best agent under these circumstances is meglumine iothalamate. What-ever the contrast medium, it should be thor-oughly and immediately washed out with elec-trolyte solution . 4200 East Ninth Avenue Denver, Colorado 80220 References 1. CORMAN, J. L. , et al.: Ex-vivo perfusion, arteriography and autotransplantation procedures for kidney salvage, Surg. Gynec. Obstet., in press. 2. CALNE, R Y.: Tumor in a single kidney: nep hrectomy, excision and autotransplantation , Lancet 2: 761 (1971). 3. HARDY, J. D.: High ureteral injuries. Management by autotransplantation of the kidney, J.A.M .A. 184: 97 (1963). 4. STARZL, T. E.: Experience in Renal Transplantation, Philadelphia, W. B. Saunders Co., 1964, p. 68. 5. BELZER, F. 0., ASHBY, B. S., and DUNPHY, J. E.: 24-Hour and 72-hour preservation of canine kidneys, Lancet 2: 536 (1967). 6. KJ'IOEFEL, P. K.: Radio Contrast Agents, in International Encyclopedia of Pharmacology and Therapeutics. Oxford, Pergamon Press Ltd., 1971, p. 261. 7. CHAPLIN, H., and CARLSSON, E.: Changes in human red blood cells during in-vitro exposure to several roentgeno-logic contrast media, Am. J. Roentgenol. 86: 1127 (1961). 8. KUTT, H., MILHORAT, T. H., and McDOWELL, F.: The effects of iodized contrast media upon blood proteins, electrolytes and red celis, Neurology 13: 492 (1963). 9. KUTT, H., et al.: Possible mechanisms of complications of angiography, Acta Radiol. (Diagn.) 5: 276 (1966). 10. ZINNER, G., and GOTTLOB, R: Morphologic changes in vessel endothelia caused by contrast media, Angiology 10: 207 (1959). 11. MERSERAU, W. A., and ROBERTSON, H. R. : Observa-tions on venou s endothelial injury following the in-jection of various radiographic contrast media in the rat, J. Neurosurg. 18: 289 (1961). 12. AUSMAN, J. I., YOUNG, R, and OWENS, G.: Radiopaque dyes and other agents in the production of endothelial damage, J. Surg. Res. 4: 349 (1964). 13. RAND, P. W., and LACOMBE, E. : Effects of angiocardio-graphic injec tions on blood viscos ity, Radiology 85: 1022 (1965). 14. ALFlDl, R. J., and MAGNUSSON, M. 0 .: Arteriography during perfusion preservation of kidneys, Am. J. Roentgenol. Radium Ther. Nucl. Med. 114: 690 (1972). UROLOGY I SEPTEMBER 1973 I VOLUME II, NUMBER 3 

Arteriography during ex vivo renal perfusion A complication

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Arteriography during ex vivo renal perfusion A complication

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