Radical nephrectomy in patients with renal cell carcinoma with venous, vena caval, and atrial extension

Radical Nephrectomy in Patients With Renal Cell Carcinoma With Venous, Vena Caval, and Atrial Extension David J. Swierzewski, BA, Mark J. Swierzewski, MD, John A. Libertino, MD, Burlington, Massachusetts BACKCROUND: F r o m July 3 1 , 1 9 6 8 , t h r o u g h August 3 1 , 1 9 9 2 , 1 0 0 patients with r e n a l cell , a r c i n o m a e x t e n d i n g into the r e n a l vein, v e n a ~,ava, a n d right a t r i u m w e r e t r e a t e d and evalu~,,ted at o u r institution. E a c h p a t i e n t u n d e r w e n t ~adical n e p h r e c t o m y with v e n a e a v o t o m y a n d ,,triotomy as c o n s i d e r e d to b e appropriate f o r , ach individual p a t i e n t ' s t u m o r t h r o m b u s . METHODS: T h e charts w e r e retrospectively ana'Jzed, and surveys w e r e sent to survivors o r , e a r e s t o f kin. RESULTS: T h e m e d i a n age was 6 1 y e a r s , and ~vo thirds o f the t u m o r s o c c u r r e d in m e n ( 6 7 ases). O f the 1 0 0 patients with r e n a l cell carcinoma resected, 13 patients ( 1 3 % ) h a d atrial exension; 7 5 patients ( 7 5 % ) had v e n a caval exension; and 12 patients ( 1 2 % ) h a d e x t e n s i o n ~nly into the r e n a l vein. Seventy-two patients 72%) had n o e v i d e n c e o f metastatic disease at he time o f surgery and h a v e a m e d i a n survival ~f 2 1 . 1 years. F i v e - y e a r survival is 6 4 % , and 0 - y e a r survival is 5 7 % . Twenty-eight patients 28%) h a d e v i d e n c e o f metastatic i n t r a o p e r a t i v e nd/or pathologically p r o v e n m e t a s t a t i c disease ~nd h a v e a m e d i a n survival o f 2 . 5 y e a r s with a ,-year survival o f 2 0 % and n o patient living beond 7 . 8 years. CONCLUSION: W e believe that an e x t e n d e d o p e r ,tion f o r r e n a l cell c a n c e r with i n v o l v e m e n t o f he r e n a l vein, v e n a cava, and right a t r i u m is a r r a n t e d in p r o p e r l y selected patients and en~wes r e a s o n a b l e l o n g - t e r m survival. the management of patients with renal cell ~q'istorically, .carcinoma with extension into the vena cava has ,roven both challenging and controversial. Numerous inestigators have reported quite varied results, which have dded to the confusion. The reported 5-year survival rate , between 25% and 57%. 1"9 We believe that proper se~'ction of patients and meticulous attention to surgical echnique will improve clinical results and diminish the ontroversy associated with this disease. • The reported incidence of renal cell adenocarcinoma in ae United States is 3.5 per 100,000 population per year. I° -~lthough renal cell carcinoma has been reported in palents of all ages from infancy to old age, the median age ~t the time of diagnosis has been reported to be between Fromthe DepartmentofUrology,LaheyClinic,BurlingtonMassachusetts. Requests for reprints should be addressed to John A. Libertino,MD, )epartment of Urology, Lahey Clinic, 41 Mall Road, Burlington, ..4assachusetts 01805. Presented at the 22nd Annual Meeting of the Society for Chnical VascularSurgery, Tucson, Arizona,March 2-6, 1994.

55 and 57 years of age. Despite numerous trials with single and multidrug chemotherapeutic regimens, radiotherapy, and hormonal manipulation, surgical extirpation remains the mainstay for curative treatment of renal cell carcinoma. In a review of 309 patients treated by radical nephrectomy between 1935 and 1965, Skinner et al I reported an operative mortality rate of 5%, with an overall survival rate of 45% at 5 years and 33% at 10 years. Excluding patients who had metastasis when first evaluated, the 5- and 10year survival rates were 57% and 44%, respectively. In recent years, Skinner et al 2 and Suggs et al5 have reported 5-year survival rates of 57% for patients with no evidence of metastases. STAGING In order to standardize the evaluation of the efficacy of treatment and the prognosis of individual patients, Hocks and Kadesky u proposed a pathologic staging system that was later modified by Robson et al. 12,13 Although several tumor, node, and metastases (TNM) systems have been proposed, none has proven totally effective in addressing all the issues associated with accurate staging of renal cancer. Currently, the staging system of choice is Robson's modification: Stage I: Tumor confined within the renal capsule without involvement of the perinephric fat. Stage II: Tumor invasion of perinephric fat but confined to Gerota's fascia. Stage HI: Tumor involves the renal vein or the regional lymph nodes or both with or without involvement of the vena cava or perinephric fat. Stage IV: Distant metastasis or histologic involvement of contiguous visceral structures. When survival rates were assessed using this system, Skinner and associates I reported that, of 102 patients with stage I cancer, 65% survived 5 years and 56% survived 10 years; of 22 patients with stage II cancer, 47% survived 5 years and 20% survived 10 years; of 108 patients with stage III cancer, 51% survived 5 years and 37% survived 10 years; and of 77 patients with stage IV cancer, 8% survived 5 years and 7% survived 10 years. A problem with Robson's modified staging system is evident when one examines stage HI disease. Patients with renal vein or caval involvement, but without nodal or perinephric involvement, have had survival rates similar to patients categorized with stage I disease. 1.12,14,1S In our experience of 100 patients with extension of renal cell carcinoma to the vena cava treated by thoraco-abdominal radical nephrectomy and partial resection of the vena cava, survival rates were excellent when involvement of nodes was absent. Involvement of perinephric fat did not influence survival.

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Intracaval tumor thrombus is usually a manifestation of advanced renal cell carcinoma, but occasionally may be associated with Wilms' tumor and adrenal carcinoma. Approximately 5% of patients undergoing radical nephrectomy for renal cell carcinoma have extension of tumor thrombus into the inferior vena cava. The level of extension varies from a small tongue of thrombus at the level of the renal vein to an extensive thrombus into the fight atrium. Our study had 12 patients with thrombus involvement at the level of the renal vein, 75 patients with thrombus involving the vena cava, and 13 patients with thrombus involving the right atrium. SYMPTOMS AND SIGNS Most patients present with symptoms and signs typical of renal carcinoma, with hematuria, flank or abdominal pain, and a flank or abdominal mass predominating. However, one third to one half of patients demonstrate signs or symptoms directly referable to involvement of the vena cava. The diagnosis of extension to the vena cava should be suspected when bilateral lower extremity edema, fight varicocele or left varicocele of recent onset, dilated superficial abdominal wall veins, caput medusae, pulmonary embolus, or proteinuria is noted in association with a renal tumor. PREOPERATIVE TESTS Since renal cell carcinoma is primarily a radiologic diagnosis, and since the presence or absence of metastasis is paramount in treatment decisions, all patients should be evaluated with computed tomography, lung tomography, bone scan, liver function tests, and selective renal arteriography. Extension to the vena cava must be considered (and consequently inferior venacavography is indicated) when a perihilar mass associated with a nonfunctioning kidney is seen on excretory urography, filling defects are noted on the venous phase of arteriography, and involvement of the renal vein or vena cava is suspected on computed tomography or ultrasonography. Superior venacavography is indicated in the presence of total occlusion of the vena cava or when the uppermost limit of the vena caval extension cannot be determined clearly by inferior venacavography. In addition to superior venacavography, a study of the right side of the heart may be warranted in patients demonstrating complete occlusion of the inferior vena cava. Preoperative studies must delineate the proximal and distal limits of the tumor thrombus so that the appropriate surgical approach can be employed. The advent of new radiologic techniques, ie, magnetic resonance imaging (MR/), has led some to question the usefulness and efficacy of venacavography. Straton et a116 reported a case in which MR/demonstrated the superior extent of a thrombus to be at the level of the hepatic veins. However, a preoperative venacavography showed extension into the fight atrium, which was confirmed surgically; thus demonstrating that, although MR/offers several advantages over venacavography, such as that it is not invasive, no contrast-associated risks or radiation exposure is present, and it will be less time consuming as fast scanning sequences are developed, it still may not replace venacavography. Hatcher et al )7 examined the accuracy of 206

venacavography in staging renal cell carcinoma involvin[ the vena cava. They demonstrated 95% precision in est~ mating the extent of thrombus. Both investigators 16,17sug gest that MRI and other new radiologic techniques be usec in a complementary rather than mutually exclusive lash ion with venacavography when evaluating patients witt stage IliA disease. The preoperative evaluation of a patient with a tumo thrombus in the vena cava cannot be overemphasized. Th presence of perihilar nodal involvement as well as distar, visceral and bony metastasis must be excluded for an, hope of cure. The level of vena caval involvement mus also be determined so that the surgeon can plan a safe op erative approach and anticipate any special maneuvers th~ may be required during resection. SURGICAL TECHNIQUE Certain principles apply to the performance of vena cav~ surgery for renal cell tumor thrombus, regardless of th level of tumor thrombus. This is primarily a vena caw operation, and, therefore, the operative approach should b from the right side, even if the tumor thrombus extend from a left renal tumor. As in all cancer surgery, manip~ lation of the renal vein and vena cava should be kept to minimum until a DeWeese clip (Jobst, Boston, Ma.~ sachasetts) is temporarily placed on the vena cava abov the tumor thrombus to avoid dislodgement and disseml nation of tumor emboli. If a venacavotomy is required, th surgeon must gain control of the vena cava above and lx low the tumor thrombus. Finally, knowledge of the venou drainage of the kidney is essential in planning the oper~ tive procedure. Whereas the right kidney has very little collateral w nous drainage, the left kidney is endowed with abundat collateral drainage through the gonadal, adrenal, and lurr bar veins. This assumes surgical importance when rad cal nephrectomy with partial or total vena caval resectio is contemplated. No problems are encountered when rigl radical nephrectomy is performed in association wit complete vena caval resection. The left renal vein can ust ally be divided with relative impunity, relying on the le kidney's extensive venous collateral network for drainag( We always ascertain the integrity of the venous collaterl system by cross-clamping the left renal vein and occlu( ing the right ureter. Failure to observe bluish discoloratic of the urine 10 to 12 minutes after the intravenous inje( tion of 1 ampule of methylene blue dye precludes lig~ tion of the left renal vein. Cross-clamping the left ren, vein rarely proves to be problematic when this ph( nomenon is observed. Complete resection of the vena cava in conjunction wil left radical nephrectomy poses a more difficult problel that requires elaborate surgical maneuvers. The surge¢ must create venous outflow for the fight kidney by inte posing a segment of the saphenous vein either from tt fight renal vein to the vena cava above the point of rese, tion or to the portal vein. A fight eighth or ninth intercostal thoraco-abdominal cision is employed because this primarily vena caval o] eration is best approached and controlled through the fig side of the chest. For a left-sided tumor, the abdomin

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portion of the incision is extended across the midline beyond the lateral border of the left rectus muscle. The abdominal portion is opened initially to assess operability and to rule out the presence of liver metastasis, invasion of the mesocolon, the presence of involved pedhilar nodes, or extension of the tumor into the posterior musculature. The presence of any of these conditions precludes an extensive vena caval operation because the patient has a poor prognosis. If the abdominal exploration proves negative, ~he thoracic extension of the incision is completed. For right-sided tumors, the right colon is mobilized from ~he hepatic flexure to the cecum, since it is the small bowel mesentery to the ligament of Treitz. A Kocher maneuver ,s used to mobilize the second portion of the duodenum md the head of the pancreas. The colon and small bowel ire elevated out of the abdomen and inserted into a moistreed Lahey bag and placed on the chest wall. In the per~'ormance of this maneuver, the superior mesenteric artery s elevated; this affords excellent visualization and access .o the left renal vein as it crosses over the aorta just infe,ior to the superior mesentefic artery. Undue tension placed 9n the superior mesenteric artery may have a disastrous effect on the blood supply to the small bowel. Before dissection begins, a DeWeese clip is placed on the vena cava, and the fight renal artery is ligated and divided. The origin of the right renal artery from the aorta is located directly behind the left renal vein. The vein is elevated gen.ly, and the artery is ligated at its origin from the aorta. ~eoperative embolization may be employed for a large tu-nor to reduce the size of the kidney and to allow easy ac:ess to the vena caval portion of the procedure. The right enal vein is isolated but is not divided at this time. If the tumor involves only the renal vein or is a small 9rotruding tongue into the vena cava, the tumor may be milked proximally into the renal vein far enough to allow olacement of a C-shaped DeBakey or Satinsky clamp in,:orporating the renal vein and a portion of the vena cava. Fhis allows removal of the kidney with a cuff of vena cava ~vhile obviating the need to clamp the left renal vein, vena cava, or lumbar veins. If the tumor thrombus extends into the vena cava to a level where it cannot be resected in this manner, the enrare vena cava must be mobilized to a level above the tumor thrombus. In this event, access to the vena cava is best achieved by performing a Langenbeck maneuver by dividing the right triangular and coronary ligaments and rotating the right lobe of the liver medially. With careful dissection, the minor and major hepatic veins are isolated. The minor veins, usually two or three in number, are di,vjded to avoid disrupting them inadvertently during the procedure and causing unnecessary and troublesome bleeding. Again, before the vena cava is mobilized, a DeWeese clip is placed above the tumor thrombus to prevent the possibility of a tumor pulmonary embolus. This clip is left in place until the operation is completed, and then it is either removed or placed below the renal vein depending on whether the patient has the propensity for the development of a pulmonary embolus. Once the DeWeese clip is secured, umbilical tapes are passed around the vena cava above and below the tumor

thrombus and around the left renal vein. The lumbar veins are ligated and divided whenever possible. Depending on the collateral venous outflow, the left renal artery may need to be occluded temporarily with a microvascular bulldog clamp before occluding the left renal vein and vena cava. The Rummel tourniquets are then cinched down and the inferior vena cava opened longitudinally. The tumor thrombus is extracted by blunt dissection with an elevator or Penfield dissector. Often the most distal portion of the tumor thrombus is actually blood clot, which is easily dissected from the caval wall. When tumor invades the vena cava, it usually is limited to the ostium of the renal vein. To ensure complete removal of tumor, a cuff of vena cava is excised in continuity with the right kidney. The venacavotomy is closed with a continuous 5-0 Surgilene suture (Davis & Geck, Manati, Puerto Rico). Just before the closure is completed, the distal caval clamp is released to fill the vena cava and lessen the chance of an air embolus. The tourniquets are then removed in the following order: the distal caval tape, the proximal caval tape, the left renal vein tourniquet, and, finally, the left renal artery tourniquet. When the tumor extends above the level of the hepatic veins or is in the intrapericardial portion of the vena cava, the DeWeese clip must be. placed at this level. In addition, it may be necessary to place a Fogarty vascular clamp on the porta hepatis (Pringle maneuver) to control the arterial and venous inflow into the liver and also across the major hepatic veins to prevent back bleeding when the venacavotomy is created. When the tumor thrombus extends into the supradiaphragmatic vena cava, the operative approach is determined by the presence or absence of intra-atrial tumor. In the absence of intra-atrial tumor, a DeWeese clip is placed around the intrapericardial inferior vena cava, and the tumor thrombus is extracted from below the diaphragm using the method previously described. Cardiopulmonary bypass is not needed in this situation. C A R D I O P U L M O N A R Y BYPASS The presence of tumor within the fight atrium requires the use of atriotomy and cardiopulmonary bypass. This technique is described in detail elsewhere. ~s In this select group of patients, a chevron incision combined with median stemotomy provides the best exposure. Cardiopulmonary bypass is not performed until the entire kidney has been mobilized, being attached only by the renal vein. This portion of the procedure must be carried out before systemic beparinization, required for cardiopulmonary bypass, is instituted to avoid excessive bleeding. For cardiopulmonary bypass, the heart is cannulated with the arterial remm by means of the ascending aorta and the venous drainage by means of the superior vena cava and the right common femoral vein. Bypass is then instituted, the right atrium is opened, and the intra-atrial portion of the tumor is removed. Attention is next directed to the infradiaphragmatic portion of the procedure using the technique described previously. After complete removal of the tumor thrombos, the atn'otomy and vena cava are sequentially closed, and the patient is removed from cardiopulmonary bypass.

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RENAL CELL CARCINOMMSWIERZEWSKI ET AL

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Figure 4. A companson of survival based on perlnephric fat Involvement (METS negative) ~n patients with renal cell cancer.

SURVIVAL Using these methods, we have attained results that are comparable or superior to those of previous reports. I-9 In the overall group of patients who have undergone thoracoabdominal radical nephrectomy with excision of caval thrombus, we have achieved an overall adjusted 5-year survival rate of 54% and a 10-year survival of 46% with a median survival time of 5.1 years (Figure 1). We have found a statistically significant correlation between pathologic staging and survival. Patients in the unfavorable category, that is, patients with metastatic disease discovered before or at the time of operation or with positive nodes, had a mean survival time of 2.5 years with a 5-year survival of 19.6% with no patient living beyond 7.8 years (Figure 2). Patients free of nodal or metastatic disease have a median survival of 21.1 years with a 5-year survival of 64% and a 10-year survival of 57% (Figure 3). Our data demonstrate that the involvement of perinephric fat does not significantly influence survival (Figure 4, P = 0.452). The level of tumor extension and survival rates were compared and indicated no significant difference when comparing renal vein to vena cava, and the presence or absence of atrial involvement, P = 0.67 and P = 0.947, respectively. Chronic renal failure requiring chronic dialysis did not develop in any patient in our series. This is in contradistinction to other reported series 3.4 and may be attributed to

meticulous technique, which includes every effort to avoid occlusion of the venous outflow of the contralateral kidney and favors partial rather than complete caval resection.

208

CONCLUSIONS Based on our experience with 100 patients, we believe that extended surgery for renal cell carcinoma with vena caval involvement is warranted and provides reasonable long-term survival in carefully selected patients. Every effort must be made to exclude the presence of metastatic disease or regional node involvement before proceeding with such radical extirpative surgery. The presence of metastatic disease or nodal involvement, on the basis of our experience, precludes consideration of vena caval surgery. REFERENCES !. Skinner DG, Pfister RF, Colvm R. Extension of renal cell carcinoma into the vena cava. the rationale for aggressive surgical management. J Urol. 1972;107:711-716. 2. Skinner DG, Pritchen TR, Lieskovsky G, et al. Vena caval involvement by renal cell carcinoma. Surgical resection provides meaningful long-term survtval. Ann Surg. 1989;210:387-394. 3. Schefft P, Novick AC, Straffon RA, Stewart BH. Surgery for renal cell carcinoma extending into the inferior vena cava. J Urol. 1978; 120:28-31

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4 Keamey GP, Waters WB, Klein LA, et al. Results of inferior vena cava resection for renal cell carcinoma. J tirol. 1981;125:769-773. 5 Suggs WD, Smith RB HI, Dodson "IF, et al. Renal cell carcinoma with inferior vena caval involvement. J Vasc Surg. 1991;14:43--48. 6 Cherrie RJ, Goldman DG, Lindner A, deKernion JB. Prognostic ,replications of vena caval extension of renal cell carcinoma. J Urol. 1~)82;128:910-912. 7 Sogani PC, Herr HW, Bains MS, Whitmore WF. Renal cell carcmoma extending into the inferior vena cava. J tirol. 1983;130: t 60--663. 8 Montie JE, Jackson CL, Cosgrove DM, et al. Resection of large t~fenor vena cava thrombi from renal cell carcinoma with the use of t rculatory arrest. J Urol. 1988;139:25-28. t Hatcher PA, Anderson EE, Paulson DF, et al. Surgical manage,ent and prognosis of renal cell carcinoma invading the vena cava. . Urol. 1991;145:20-24. ). MacDonald EJ. Present incidence and survival picture in cancer ad promise of improved prognosis. Bull Am CoU Surg. 1948; k75-93. I Flocks RH, Kadesky MC. Malignant neoplasms of the kidney:

an analysis of 353 patients followed five years or more. J Urol. 1958;79:196-201. 12. Robson CJ. Radical nephrectomy for renal cell carcinoma. J Urol. 1963;89:37-42. 13. Robson CJ, Churchhill BM, Anderson W. The results of radical nephrectomy for renal cell carcinoma. Trans Am Assoc Genitourin Surg. 1968;60:122-129. 14. Middleton RG, Presto AJ IU. Radical thoracoabdominal nephrectomy for renal cell carcinoma. J Urol. 1973;110:36-37. 15. Ochsner MG, Brannan W, Pond HS III, Goodier EH. Renal cell carcinoma: a review of 26 years of experience at the Ochsner Clinic. J Urol. 1973;I 10:643--646. 16. Straton CS, Libertano JA, Larsen CR. Is magnetic resonance imaging alone accurate enough in staging renal cell carcinoma? Urology. 1992;40:351-353. 17. Hatcher PA, Paulson DF, Anderson EE. Accuracy in staging of renal cell carcinoma involving vena cava. Urology. 1992;39:27-30. 18. Shahlan DM, Libertino JA, Zinman LN, et al. Resection of cavoatrial renal cell carcinoma employing total circulatory arrest. Arch Surg. 1990;125:727-732.

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