Leiomyosarcoma Diagnosis David C.
and
of the Inferior Vena Cava
Surgical Management
Brewster, MD; Cristos
A.
Athanasoulis, MD;
R. Clement
\s=b\ Leiomyosarcoma of vascular origin are rare tumors arising most frequently from the inferior vena cava (IVC). We report on three patients one of whom underwent definitive resection. These tumors most commonly involve the upper segment of the IVC, and appear with manifestations of the Budd-Chiari syndrome. Lesions at this level are not amenable to surgical therapy. Tumors of the middle and lower segments of the IVC usually cause right-sided pain. Diagnosis is difficult, but is best approached preoperatively by angiography and vena cavography. Optimal therapy of lesions at these levels is surgical resection. Resection of the IVC below the hepatic veins is possible with renal function preserved by collateral drainage of the left renal vein.
(Arch Surg 111:1081-1085, 1976) of
vascular
is
primary origin Lei o myosarcoma commonly arising Primary leiomyosarcomas large major
a
rare,
from smooth-muscle tumor most of veins are veins. approximately five times more frequent than those arising in arteries, and of these more than one half have occurred in the inferior vena cava.1 Perl7' first described a leiomyosarcoma of the inferior vena cava, found at autopsy, in 1871. A recent comprehen¬ sive review by Kevorkian and Cento1 cited 33 cases, and we have collected 12 additional reports from the literature.'17' This report includes three patients with leiomyosarcoma of the inferior vena cava recently seen at the Massachusetts General Hospital, bringing the total cases to our knowl¬ edge described in the world literature to 48. REPORT OF CASES Case 1.—This 54-year-old woman was admitted to a suburban hospital with a seven-month history of progressive dyspnea on exertion, swelling of the lower extremities, increasing abdominal girth, and weight gain. She was found to have a right-sided pleural effusion and ascites. An upper gastrointestinal x-ray series, barium enema, and intravenous pyelogram were normal. Results
Accepted
for publication May 18, 1976. From the General Surgical Services (Drs Brewster and Darling) and Department of Radiology (Dr Athanasoulis), Massachusetts General Hospital, and the departments of surgery and radiology, Harvard Medical School, Boston. Reprint requests to 3 Hawthorne Place, Boston, MA 02114 (Dr Brews-
ter).
Darling, MD of liver function tests were elevated. She underwent laparotomy with findings of several liters of grossly bloody fluid. All organs were normal except the liver, which was tensely swollen, and the region of the head of the pancreas, which was firm and nodular, suggesting a mass. A liver biopsy specimen showed severe central lobular congestion and hemorrhagic necrosis. The patient was transferred to this hospital, where physical examination confirmed a right-sided pleural effusion, a tender enlarged liver, ascites, and peripheral edema. Laboratory studies showed the following levels: bilirubin, 2.7 mg/100 ml; serum glutamic oxaloacetic transaminase (SGOT), 328 units; alkaline phosphatase, 6.4 Bodansky units; and serum albumin, 3.2 gm/100 ml. Selective angiography and superior and inferior vena cavography demonstrated a right upper quadrant tumor mass with total occlusion of the inferior vena cava from LI to above the hepatic veins (Fig 1). A diagnosis of Budd-Chiari syndrome due to a leiomyosarcoma of the inferior vena cava was presumed from the clinical and angiographie data, and was confirmed at autopsy examination six months later. Case 2.-This 51-year-old man was well until six weeks prior to admission to hospital, when he noted the sudden onset of right flank pain and weakness. He was admitted to a local hospital and evaluated for possible renal disease. The blood urea nitrogen and creatinine levels rose to 37 mg/100 ml and 5.2 mg/100 ml, respectively, and returned to normal. Right-sided pain radiating to the groin and a low-grade fever persisted. An intravenous pyelogram revealed enlarged kidneys without obstruction, and an upper gastrointestinal x-ray series, oral cholecystogram, and barium enema were normal. The patient was transferred to this hospital for further evalua¬ tion. Examination revealed a temperature of 38 C (110.6 F), mild tenderness at the right costovertebral angle, and the suggestion of a mass in the right flank. There was no edema. Laboratory values were within normal limits. A second intravenous pyelogram demonstrated normal upper tracts but suggested a defect on the right wall of the bladder from an extrinsic mass. This was confirmed by a cinecystogram. Laparotomy via a right-sided paramedian incision revealed a large retroperiotoneal mass sitting atop the lower pole of the kidney. Dissection demonstrated that it originated from the inferior vena cava just below the renal veins, with complete thrombosis of the vena cava to at least this level. The mass was only partially resected, as full resection could not safely be achieved through the paramedian incision. Pathological examination of the mass revealed a leiomyosar¬ coma. Postoperatively, selective angiography and vena cavography were carried out to evaluate possible further surgical
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Fig 1.—Case 1. Left, Inferior vena cavagram shows complete obstruction of inferior vena cava at level of renal veins (arrow). Large collaterals via lumbar and azygos veins are present (curved arrows). Center, Selective hepatic venography with catheter introduced from antecubital vein shows tumor thrombus obstructing right hepatic vein (arrow). Inferior vena cava was obstructed to level of hepatic veins. Right, Selective hepatic arteriogram shows tumor stain (arrow) and tumor vessels arising from hepatic artery.
therapy,
and chemotherapy was begun with doxorubicin hydro¬ chloride (Adriamycin). Angiography demonstrated a large mass with occlusion of the vena cava to the level of the hepatic veins. Progressive abdominal ascites developed and the SGOT level rose to 2,400 units, suggesting hepatic necrosis from hepatic vein occlusion. The patient's condition slowly improved, but further surgery was not believed possible and he died at home three months later. No postmortem examination was obtained. Case 3.-This 52-year-old woman was first admitted to an outlying hospital with eight months' history of intermittent right lower quadrant pain, nausea, and a 9.1-kg weight loss. An upper gastrointestinal x-ray series, barium enema, and intravenous pyelogram were normal. Adhesions from a prior hysterectomy were thought to be the most likely cause of her symptoms. Abdominal exploration revealed normal findings except for a mass, approximately 8 cm in size, thought to be in the head of the pancreas. She was transferred to our hospital for further ther¬ apy. On admission, physical examination was unremarkable. There were no abdominal tenderness, masses, organomegaly, peripheral edema, or jaundice. All laboratory data were within normal limits. Reexploration was carried out two weeks following the first procedure. The duodenum and head of the pancreas could be mobilized off a retroperitoneal tumor that seemed to involve the aorta and inferior vena cava at the level of the renal veins. A biopsy specimen was obtained and the abdomen closed. Pathological examination of the specimen revealed a leiomyo¬ sarcoma. Evaluation for metastatic disease was negative. An inferior vena cavogram demonstrated displacement of the vena cava by a mass that involved principally the anterior and left lateral walls, as well as the origin of the left renal vein (Fig 2).
Aortography was unrevealing. Definitive operation was carried out via a right-sided thoracoab¬ dominal incision carried into the eighth interspace. The liver was reflected medially and control of the vena cava obtained just below the main hepatic veins and distally just above the iliac bifurcation. A 10-cm
mass arose
from the middle segment of
vena cava
and
involved the origin of the left renal vein (Fig 3). The proximal right renal artery was surrounded by tumor as it passed posterior to the vena cava, but was free distally, as was the right renal vein. The right kidney was removed and perfused with chilled renal perfusion fluid. The ureter was left intact. The tumor and vena cava were resected from the hepatic veins to just above the bifurcation, and proximal and distal ends of the vena cava oversewn. The left renal vein was ligated beyond the tumor. Transient hypotension at the time of cavai occlusion responded to colloid replacement. Although the urine output continued to be satisfactory from the left kidney, it was elected to autotransplant the right kidney to the pelvis, in order to allow use of postoperative irradiation to the tumor bed without concern of possible damage to a solitary left kidney. The patient's postoperative course was entirely satisfactory except for swelling of the legs, which responded to elevation and intermittent mechanical compressive therapy. Renal function remained normal at all times. Following discharge from the hospital, 5,500 rads of radiotherapy were delivered to the tumor bed over a six-week period. The patient remains well four months
postoperatively.
COMMENT The clinical diagnosis of leiomyosarcoma of the vena cava is extremely difficult to establish. Symptoms are frequently nonspecific and physical examination often normal. Because of its rarity, the diagnosis is usually not even considered. For these reasons, more than one-half of reported cases are autopsy findings. Of those diagnoses made at the time of surgery, the great majority were unexpected findings at operations carried out because of unexplained abdominal pain or for the suggestion of an abdominal mass. Previously described patients range in age from 27 to 83 years, with an average age of 54.4. There is striking female preponderance, with 40 of 48 cases occurring in women.
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Fig 2.—Case 3. Inferior vena cavagram in anteroposterior (left) and lateral (center) projection shows tumor mass arising from or invading wall or inferior vena cava. Surgical clips outline extent of mass lesion. Right, Selective venography shows tumor involvement of left renal vein at junction with inferior vena cava (arrow). Extensive venous collateral drainage has been established via gonadal and hemiazygos veins (curved arrows).
predilection remains unexplained. Symptoms depend largely on the location of the tumor, its rate of growth, and the presence of any associated
This
thrombosis. The inferior vena cava may be consid¬ ered in three segments: lower (below renal veins), middle (between renal and hepatic veins), and upper (above the hepatic veins).11 Tumors of the lower segment may occur with varying degrees of edema of the lower extremities, although it is important to realize that edema may be totally absent if little intraluminal growth of the tumor has occurred, or if cavai obstruction has been gradual enough to allow adequate collateral venous circulation to develop. In general, significant edema is infrequent unless sudden occlusion due to secondary venous thrombosis has occurred. A more frequent symptom is abdominal pain, usually in the lower right side of the abdomen, flank, or low back.14 Often, this has been present for a considerable period and presum¬ ably attests to the slow growth and often prolonged course of these tumors. One case report described symptoms of 13 years' duration thought attributable to the tumor itself.17' An abdominal mass may be appreciated, and has been noted in approximately one-half of reported cases. Leiomyosarcomas involving the middle segment of the inferior vena cava often present a similar picture. Pain may more often be located in the right upper quadrant of the abdomen and suggest biliary tract disease. However, it is usually nonradiating and unrelated to meals or gastroin¬ testinal function. Because tumors in this location may interfere with renal vein drainage, abnormalities of the urinalysis may be present, ranging from mild albuminuria to a full-blown nephrotic syndrome if extensive associated renal vein thrombosis has occurred. One case of renovas¬ cular hypertension has been described to our knowledge, attributed to invasion and compression of the renal artery
venous
by a middle-segment tumor.1" Tumors originating in or extending to the upper segment of the vena cava usually appear with varying
manifestations of the Budd-Chiari
obstruction, either by
syndrome due
to
associated venous thrombosis, of the hepatic veins. Common findings are an enlarged, tender liver, jaundice, ascites, edema of the extremities, and perhaps nausea and vomiting. On occa¬ sion, tumor growth within the lumen of the vena cava is extensive and extends into the right atrium, even obstruct¬ ing the tricuspid valve in one instance.17 Nonspecific symptoms including malaise, nausea, and weight loss are often present with tumors at all levels of the inferior vena cava. In one instance, pulmonary emboli of both tumor fragments and venous thrombi has oc¬ curred.17' Based on the highest extension of tumor, leiomyosarcomas of the inferior vena cava have unfortunately involved the upper segment most often (25 cases), while more manageable lesions of the middle and lower segments have been described in 14 and nine patients, respectively. Laboratory determinations are usually unremarkable and do not contribute to the diagnosis. Exceptions are possible urinary abnormalities with middle-segment tumors or liver function derangements in patients with a Budd-Chiari syndrome." Various laboratory abnormalities may, of course, be present in the patient with late-stage disease and distant métastases. Similarly, contrast roentgenograms of the gastrointes¬ tinal tract, kidneys, or gallbladder are frequently nondiagnostic. At best they may suggest the presence and anatomic relationships of a retroperitoneal mass, but do not reveal the organ or tissue of origin. In a patient in whom the possibility of a tumor originat¬ ing in the inferior vena cava is suspected from history, tumor
or
by
physical, examination, roentgenograms, or findings at operation, the combined use of selective arteriography and vena cavography has the greatest likelihood of suggesting the correct diagnosis." In addition, the extent of involve¬ "1S
ment of the inferior
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vena cava
and tributaries such
as
the
renal and hepatic veins can be accurately assessed preoper¬ atively. If inferior vena cavography shows complete cavai obstruction, the proximal extent should be defined by introducing a catheter from above via an antecubital vein. MANAGEMENT
Optimal therapy of leiomyosarcoma of the inferior vena is surgical resection; primary treatment with either radiotherapy or chemotherapy usually offers little bene¬ fit."" Due to the difficulties of diagnosis, these tumors may have attained considerable size. However, it is important to recognize their characteristic slow growth and relatively low malignant potential. For these reasons, métastases are
cava
present in less than one-half of
cases at the time of may usually be dissected free of all neighboring structures excepting the vena cava itself. Direct invasion of local viscera is a late and infre¬ quent finding, and therefore aggressive surgery can often achieve local resection of tumors located beneath the hepatic veins.
diagnosis,
and the tumor
3. Operative photograph of middle segment of vena Proximal and distal occlusion has been obtained and vena cava has been opened after right kidney has been removed. Tumor nodularity is present within lumen of vena cava, extending into orifice of left renal vein (arrow).
Fig 3.—Case
cava.
mass
Specific points regarding surgical management depend largely on the segment of vena cava involved and the degree and duration of obstruction that exists. As discussed, much of this vital information can be obtained from preoperative arteriography and vena cavography.
Resection of the tumor mass in the lower segment and of the involved vena cava should be feasible. Interruption of the vena cava below the renal veins is well tolerated. Tumor growth at this level may be largely extraluminal, and large tumors may involve relatively small portions of the vena cava. If truly pedunculated, only a portion of the involved wall of the vena cava may require resection with the tumor mass, and closure primarily or with a patch may preserve the continuity of the vessel.1" However, since cavai interruption at this level is so well tolerated and local recurrence common, wide resection of the infrarenal vena cava would seem most prudent. Any associated venous thrombosis present in the iliac system should be removed, if possible, to minimize the chances of troublesome post¬ operative edema." Tumors at the middle segment of the vena cava currently present the most difficult management deci¬ sions, requiring careful planning and judgment. Formerly, interruption of the vena cava above the renal veins was believed to be almost uniformly fatal. However, there are an increasing number of case reports in which interruption at this level is indeed tolerated, including ligation for acute traumatic injury18·7'"'74 and ligation or resection at the time of right nephrectomy, usually for renal carcinoma with tumor extension to the vena cava."·79 By the time of diagnosis, most leiomyosarcomas of the vena cava will have produced significant venous obstruc¬ tion. The existence of established venous collateral circula¬ tion may be confirmed by preoperative vena cavography, and it offers assurance that the suprarenal vena cava may be interrupted without undue risk of severe hypotension from an acute reduction of venous return. It is important to monitor carefully the usual parameters of volume
with administration of adequate blood and colloid solutions, deleterious hemodynamic conse¬ quences may be prevented.74-28 Following interruption of the suprarenal vena cava, previous experience has indicated that the left kidney may be expected to function satisfactorily because of its unique collateral venous tributaries not present on the right. These have been well described by Anson and Cauldwell,"' and include adrenal, gonadal, and lumbar branches, which together richly communicate with the hemiazygos, paravertebral, and ascending lumbar systems. These collateral channels allow the left renal vein to be ligated centrally with expected preservation of adequate renal venous drainage and function, although a period of diminished function may occur.7' Again, any element of gradually developing venous obstruction will have enhanced these collateral systems, and less difficulty with function of the left kidney may be anticipated. Because of the anatomic lack of similar venous tribu¬ taries available to the right renal vein, it is most unlikely that function of the right kidney will be maintained following interruption of its venous drainage. It is inter¬ esting to note that in almost all reported survivors of ligation or resection of the suprarenal vena cava, a right nephrectomy was carried out simultaneously. Similarly, experimental work in dogs has revealed an increased survival when right nephrectomy was carried out with ligation of the suprarenal vena cava, as opposed to ligation without right nephrectomy.:il·32 Adequate surgical management of tumors involving the middle segment of vena cava will therefore involve wide resection of the vena cava, often from just below the hepatic veins to above the iliac bifurcation, with ligation of the renal veins at their point of entry into the vena cava. While the left kidney may be expected to survive and maintain renal function, especially when evidence of adequate collateral circulation has been demonstrated, the right kidney must be either removed or have its venous drainage reestablished. If function of the left kidney alone is suspect, one may inject indigo carmine dye.ls If dye appears in the urinary bladder within 10 to 15 minutes, one
replacement, and
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function of the left kidney is assured and that development of renal failure is unlikely. If the right kidney appears important to maintain renal function, autotransplantation to the right pelvis, employing stan¬ dard vascular techniques without division of the ureter,371 seems the most reasonable method, as was used in case 3 of this report. Results with prosthetic replacement of the vena cava or other venous segments have been almost uniformly discouraging, while other alternatives such as portorenal anastomosis seem unnecessarily complex.7'" Adequate exposure for tumors of the middle segment is best accomplished via a right-sided thoracoabdominal inci¬ sion carried through the bed of the eighth rib. The liver may then be reflected anteriorly by division of the trian¬ gular and coronary ligaments. When combined with reflec¬ tion of the duodenum and head of the pancreas, the entire vena cava from the main hepatic veins to the iliac bifurca¬ tion may be exposed. Several small accessory hepatic veins may be encountered and divided with impunity. Unfortunately, no satisfactory surgical treatment of tumors in the upper segment of the vena cava is possible at may
assume
the
present. Theoretically,
treatment
by hepatectomy,
resec¬
tion of the vena cava, and heterotopic autotransplantation of the liver might be achievable if the hepatic veins are uninvolved by tumor extension or secondary thrombosis." Because of the propensity of these tumors to recur locally, the adjunctive use of postoperative radiotherapy to the tumor bed following surgical resection of lesions of the lower or middle segments of the vena cava seems reason¬ able. At least one report has shown radiotherapy to be helpful in the palliative management of established local recurrence.'4
Leiomyosarcoma rare
of the inferior
vena cava
remains
a
lesion, but it is being reported with increasing
frequency. Its slow growth and relatively low malignant potential offer the chance for cure or long-term palliation for those tumors below the hepatic veins. The use of preoperative angiography and vena cavography, together with modern vascular surgical and anesthetic techniques, should allow increased salvage of these difficult problems. Nonproprietary Name and Trademark of Drug Doxorubicin
hydroch\oride-Adriamycin. References
1. Kevorkian
J, Cento DP: Leiomyosarcoma of large arteries and veins.
Surgery 73:390-400,
1973. 2. Perl L: Ein fall von sarkom der vena cava inferior. Virchows Arch Pathol Anat 53:378-383, 1871. 3. Landes E: Leiomyosarcoma of the inferior vena cava. Dapim Refuiim 24:453-456, 1965. 4. Deutsch V, Fraenkel O, Frand V, et al: Leiomyosarcoma of the inferior
vena cava
propagating into the right
atrium. Br Heart J 30:571-574, 1968.
BS, McGill DAF, Williams R: Leiomyosarcoma of inferior vena cava producing Budd-Chiari Syndrome. J Pathol 104:283-286, 1971. 6. Wray RC, Dawkins H: Primary smooth muscle tumors of the inferior vena cava. Ann Surg 174:1009-1018, 1971. 7. Johansen JK, Nielsen R: Leiomyosarcoma of the inferior vena cava: Report of a case. Acta Chir Scand 137:181-184, 1971. 8. Justiniani FR, Cohen GH, Roen SA, et al: Budd-Chiari Syndrome due to leiomyosarcoma of the inferior vena cave. Am J Dig Dis 18:337-346, 5. Cardell
1973. 9. Couinaud C: Tumeurs de la veine cave inferieure. J Chir 105:411-432, 1973. 10. Stuart FP, Baker WH: Palliative surgery for leiomyosarcoma of the inferior vena cava. Ann Surg 177:237-239, 1973. 11. Kapsinow R, Brierre JT: Leiomyosarcoma of the inferior vena cava. J La State Med Soc 126:400-401, 1974. 12. DeMoulin JC, Sambon Y, Bandinet V, et al: Leiomyosarcoma of the inferior vena cava: An unusual cause of pulmonary embolism. Chest 66:597\x=req-\ 599, 1974. 13. Missal ME, Robinson JA, Tatum RW: Inferior vena cava obstruction: Clinical manifestations, diagnostic methods, and related problems. Ann Intern Med 62:133-161, 1965. 14. Jurayj MN, Midell AI, Bederman S, et al: Primary leiomyosarcomas of the inferior vena cava. Cancer 26:1349-1353, 1970. 15. Nartowicz E, Domaniewski J, Wiecko W: Leiomyosarcoma de la veine cava inferieure: Traitment errone de cholecystite. Maroc Med 47:339-340, 1967. 16. Guedon J, Mesnard J, Poison J, et al: Hypertension r\l=e'\no-vasculaire par leiomyosarcome de la veine cave inf\l=e'\rieure.Ann Med Interne 121:905\x=req-\ 912, 1970. 17. Hoffbrand AU, Lloyd-Thomas HG: Leiomyosarcoma of the inferior vena cava leading to obstruction of the tricuspid valve. Br Heart J 26:709\x=req-\ 714, 1964. 18. Caplan BB, Halasz NA, Bloomer WE: Resection and ligation of the suprarenal inferior vena cava. J Urol 92:25-29, 1964. 19. Stanley CJ, Valaitis J, Trippel OH, et al: Leiomyosarcoma of the inferior vena cava. Am J Surg 113:211-216, 1967. 20. Mehta AR, Rajpal RM, Jussawalla DJ: Suprarenal ligation of the inferior vena cava with a solitary horseshow kidney. Am J Surg 116:925-928, 1968. 21. Ramnath R, Walden EC, Caguin F: Ligation of the suprarenal vena cava and right nephrectomy with complete recovery. Am J Surg 112:88-90, 1966. 22. Waltuck TL, Crow RW, Humphrey LJ, et al: Avulsion injuries of the vena cava following blunt abdominal trauma. Ann Surg 171:67-72, 1970. 23. Bolot F, Germain J, Ponsan R, et al: Blessure par bulle de la veine cava inferieure au dessus des pedicules renaux. Mem Acad Chir 81:394-398, 1955. 24. Gazzaniga AB, Colodny AH: Long-term survival after acute ligation of the vena cava above the renal veins. Ann Surg 175:563-568, 1972. 25. McCullough DL, Gittes RF: Ligation of the renal vein in the solitary kidney: Effects on renal function. J Urol 113:295-298, 1975. 26. Skinner DG, Pfister RF, Calvin R: Extension of renal cell carcinoma into the vena cava: The rationale for aggressive surgical management. J Urol 107:711-715, 1972. 27. Clark CD: Survival after excision of a kidney, segmental resection of the vena cava, and division of the opposite renal vein. Lancet 2:1015-1018, 1961. 28. Pathak IC: Survival after right nephrectomy, excision of infrahepatic vena cava, and ligation of left renal vein: A case report. J Urol 106:599-602, 1971. 29. Duckett JW, Lifland JH, Peters PC: Resection of the inferior vena cava for adjacent malignant diseases. Surg Gynecol Obstet 136:711-716, 1973. 30. Anson BJ, Cauldwell EW: The pararenal vascular system. Q Bull Northwestern Univ Med School 21:320-328, 1947. 31. Sapirstein LA, Reininger EJ: Catheter-induced error in hepatic venous sampling. Circ Res 4:493-496, 1956. 32. Lespinasse V: Ligation of the vena cava above the renal veins with or without nephrectomy. Q Bull Northwestern Univ Med School 21:312-316, 1947. 33. Corman JL, Anderson JT, Taubman J, et al: Ex vivo perfusion, angiography and autotransplantation procedures for kidney salvage. Surg Gynecol Obstet 137:659-665, 1973. 34. Allan J, Burnett W, Lee FD: Leiomyosarcoma of the inferior vena cava. Scott Med J 9:352-355, 1964.
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and
of the Inferior Vena Cava
Surgical Management
Brewster, MD; Cristos
A.
Athanasoulis, MD;
R. Clement
\s=b\ Leiomyosarcoma of vascular origin are rare tumors arising most frequently from the inferior vena cava (IVC). We report on three patients one of whom underwent definitive resection. These tumors most commonly involve the upper segment of the IVC, and appear with manifestations of the Budd-Chiari syndrome. Lesions at this level are not amenable to surgical therapy. Tumors of the middle and lower segments of the IVC usually cause right-sided pain. Diagnosis is difficult, but is best approached preoperatively by angiography and vena cavography. Optimal therapy of lesions at these levels is surgical resection. Resection of the IVC below the hepatic veins is possible with renal function preserved by collateral drainage of the left renal vein.
(Arch Surg 111:1081-1085, 1976) of
vascular
is
primary origin Lei o myosarcoma commonly arising Primary leiomyosarcomas large major
a
rare,
from smooth-muscle tumor most of veins are veins. approximately five times more frequent than those arising in arteries, and of these more than one half have occurred in the inferior vena cava.1 Perl7' first described a leiomyosarcoma of the inferior vena cava, found at autopsy, in 1871. A recent comprehen¬ sive review by Kevorkian and Cento1 cited 33 cases, and we have collected 12 additional reports from the literature.'17' This report includes three patients with leiomyosarcoma of the inferior vena cava recently seen at the Massachusetts General Hospital, bringing the total cases to our knowl¬ edge described in the world literature to 48. REPORT OF CASES Case 1.—This 54-year-old woman was admitted to a suburban hospital with a seven-month history of progressive dyspnea on exertion, swelling of the lower extremities, increasing abdominal girth, and weight gain. She was found to have a right-sided pleural effusion and ascites. An upper gastrointestinal x-ray series, barium enema, and intravenous pyelogram were normal. Results
Accepted
for publication May 18, 1976. From the General Surgical Services (Drs Brewster and Darling) and Department of Radiology (Dr Athanasoulis), Massachusetts General Hospital, and the departments of surgery and radiology, Harvard Medical School, Boston. Reprint requests to 3 Hawthorne Place, Boston, MA 02114 (Dr Brews-
ter).
Darling, MD of liver function tests were elevated. She underwent laparotomy with findings of several liters of grossly bloody fluid. All organs were normal except the liver, which was tensely swollen, and the region of the head of the pancreas, which was firm and nodular, suggesting a mass. A liver biopsy specimen showed severe central lobular congestion and hemorrhagic necrosis. The patient was transferred to this hospital, where physical examination confirmed a right-sided pleural effusion, a tender enlarged liver, ascites, and peripheral edema. Laboratory studies showed the following levels: bilirubin, 2.7 mg/100 ml; serum glutamic oxaloacetic transaminase (SGOT), 328 units; alkaline phosphatase, 6.4 Bodansky units; and serum albumin, 3.2 gm/100 ml. Selective angiography and superior and inferior vena cavography demonstrated a right upper quadrant tumor mass with total occlusion of the inferior vena cava from LI to above the hepatic veins (Fig 1). A diagnosis of Budd-Chiari syndrome due to a leiomyosarcoma of the inferior vena cava was presumed from the clinical and angiographie data, and was confirmed at autopsy examination six months later. Case 2.-This 51-year-old man was well until six weeks prior to admission to hospital, when he noted the sudden onset of right flank pain and weakness. He was admitted to a local hospital and evaluated for possible renal disease. The blood urea nitrogen and creatinine levels rose to 37 mg/100 ml and 5.2 mg/100 ml, respectively, and returned to normal. Right-sided pain radiating to the groin and a low-grade fever persisted. An intravenous pyelogram revealed enlarged kidneys without obstruction, and an upper gastrointestinal x-ray series, oral cholecystogram, and barium enema were normal. The patient was transferred to this hospital for further evalua¬ tion. Examination revealed a temperature of 38 C (110.6 F), mild tenderness at the right costovertebral angle, and the suggestion of a mass in the right flank. There was no edema. Laboratory values were within normal limits. A second intravenous pyelogram demonstrated normal upper tracts but suggested a defect on the right wall of the bladder from an extrinsic mass. This was confirmed by a cinecystogram. Laparotomy via a right-sided paramedian incision revealed a large retroperiotoneal mass sitting atop the lower pole of the kidney. Dissection demonstrated that it originated from the inferior vena cava just below the renal veins, with complete thrombosis of the vena cava to at least this level. The mass was only partially resected, as full resection could not safely be achieved through the paramedian incision. Pathological examination of the mass revealed a leiomyosar¬ coma. Postoperatively, selective angiography and vena cavography were carried out to evaluate possible further surgical
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Fig 1.—Case 1. Left, Inferior vena cavagram shows complete obstruction of inferior vena cava at level of renal veins (arrow). Large collaterals via lumbar and azygos veins are present (curved arrows). Center, Selective hepatic venography with catheter introduced from antecubital vein shows tumor thrombus obstructing right hepatic vein (arrow). Inferior vena cava was obstructed to level of hepatic veins. Right, Selective hepatic arteriogram shows tumor stain (arrow) and tumor vessels arising from hepatic artery.
therapy,
and chemotherapy was begun with doxorubicin hydro¬ chloride (Adriamycin). Angiography demonstrated a large mass with occlusion of the vena cava to the level of the hepatic veins. Progressive abdominal ascites developed and the SGOT level rose to 2,400 units, suggesting hepatic necrosis from hepatic vein occlusion. The patient's condition slowly improved, but further surgery was not believed possible and he died at home three months later. No postmortem examination was obtained. Case 3.-This 52-year-old woman was first admitted to an outlying hospital with eight months' history of intermittent right lower quadrant pain, nausea, and a 9.1-kg weight loss. An upper gastrointestinal x-ray series, barium enema, and intravenous pyelogram were normal. Adhesions from a prior hysterectomy were thought to be the most likely cause of her symptoms. Abdominal exploration revealed normal findings except for a mass, approximately 8 cm in size, thought to be in the head of the pancreas. She was transferred to our hospital for further ther¬ apy. On admission, physical examination was unremarkable. There were no abdominal tenderness, masses, organomegaly, peripheral edema, or jaundice. All laboratory data were within normal limits. Reexploration was carried out two weeks following the first procedure. The duodenum and head of the pancreas could be mobilized off a retroperitoneal tumor that seemed to involve the aorta and inferior vena cava at the level of the renal veins. A biopsy specimen was obtained and the abdomen closed. Pathological examination of the specimen revealed a leiomyo¬ sarcoma. Evaluation for metastatic disease was negative. An inferior vena cavogram demonstrated displacement of the vena cava by a mass that involved principally the anterior and left lateral walls, as well as the origin of the left renal vein (Fig 2).
Aortography was unrevealing. Definitive operation was carried out via a right-sided thoracoab¬ dominal incision carried into the eighth interspace. The liver was reflected medially and control of the vena cava obtained just below the main hepatic veins and distally just above the iliac bifurcation. A 10-cm
mass arose
from the middle segment of
vena cava
and
involved the origin of the left renal vein (Fig 3). The proximal right renal artery was surrounded by tumor as it passed posterior to the vena cava, but was free distally, as was the right renal vein. The right kidney was removed and perfused with chilled renal perfusion fluid. The ureter was left intact. The tumor and vena cava were resected from the hepatic veins to just above the bifurcation, and proximal and distal ends of the vena cava oversewn. The left renal vein was ligated beyond the tumor. Transient hypotension at the time of cavai occlusion responded to colloid replacement. Although the urine output continued to be satisfactory from the left kidney, it was elected to autotransplant the right kidney to the pelvis, in order to allow use of postoperative irradiation to the tumor bed without concern of possible damage to a solitary left kidney. The patient's postoperative course was entirely satisfactory except for swelling of the legs, which responded to elevation and intermittent mechanical compressive therapy. Renal function remained normal at all times. Following discharge from the hospital, 5,500 rads of radiotherapy were delivered to the tumor bed over a six-week period. The patient remains well four months
postoperatively.
COMMENT The clinical diagnosis of leiomyosarcoma of the vena cava is extremely difficult to establish. Symptoms are frequently nonspecific and physical examination often normal. Because of its rarity, the diagnosis is usually not even considered. For these reasons, more than one-half of reported cases are autopsy findings. Of those diagnoses made at the time of surgery, the great majority were unexpected findings at operations carried out because of unexplained abdominal pain or for the suggestion of an abdominal mass. Previously described patients range in age from 27 to 83 years, with an average age of 54.4. There is striking female preponderance, with 40 of 48 cases occurring in women.
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Fig 2.—Case 3. Inferior vena cavagram in anteroposterior (left) and lateral (center) projection shows tumor mass arising from or invading wall or inferior vena cava. Surgical clips outline extent of mass lesion. Right, Selective venography shows tumor involvement of left renal vein at junction with inferior vena cava (arrow). Extensive venous collateral drainage has been established via gonadal and hemiazygos veins (curved arrows).
predilection remains unexplained. Symptoms depend largely on the location of the tumor, its rate of growth, and the presence of any associated
This
thrombosis. The inferior vena cava may be consid¬ ered in three segments: lower (below renal veins), middle (between renal and hepatic veins), and upper (above the hepatic veins).11 Tumors of the lower segment may occur with varying degrees of edema of the lower extremities, although it is important to realize that edema may be totally absent if little intraluminal growth of the tumor has occurred, or if cavai obstruction has been gradual enough to allow adequate collateral venous circulation to develop. In general, significant edema is infrequent unless sudden occlusion due to secondary venous thrombosis has occurred. A more frequent symptom is abdominal pain, usually in the lower right side of the abdomen, flank, or low back.14 Often, this has been present for a considerable period and presum¬ ably attests to the slow growth and often prolonged course of these tumors. One case report described symptoms of 13 years' duration thought attributable to the tumor itself.17' An abdominal mass may be appreciated, and has been noted in approximately one-half of reported cases. Leiomyosarcomas involving the middle segment of the inferior vena cava often present a similar picture. Pain may more often be located in the right upper quadrant of the abdomen and suggest biliary tract disease. However, it is usually nonradiating and unrelated to meals or gastroin¬ testinal function. Because tumors in this location may interfere with renal vein drainage, abnormalities of the urinalysis may be present, ranging from mild albuminuria to a full-blown nephrotic syndrome if extensive associated renal vein thrombosis has occurred. One case of renovas¬ cular hypertension has been described to our knowledge, attributed to invasion and compression of the renal artery
venous
by a middle-segment tumor.1" Tumors originating in or extending to the upper segment of the vena cava usually appear with varying
manifestations of the Budd-Chiari
obstruction, either by
syndrome due
to
associated venous thrombosis, of the hepatic veins. Common findings are an enlarged, tender liver, jaundice, ascites, edema of the extremities, and perhaps nausea and vomiting. On occa¬ sion, tumor growth within the lumen of the vena cava is extensive and extends into the right atrium, even obstruct¬ ing the tricuspid valve in one instance.17 Nonspecific symptoms including malaise, nausea, and weight loss are often present with tumors at all levels of the inferior vena cava. In one instance, pulmonary emboli of both tumor fragments and venous thrombi has oc¬ curred.17' Based on the highest extension of tumor, leiomyosarcomas of the inferior vena cava have unfortunately involved the upper segment most often (25 cases), while more manageable lesions of the middle and lower segments have been described in 14 and nine patients, respectively. Laboratory determinations are usually unremarkable and do not contribute to the diagnosis. Exceptions are possible urinary abnormalities with middle-segment tumors or liver function derangements in patients with a Budd-Chiari syndrome." Various laboratory abnormalities may, of course, be present in the patient with late-stage disease and distant métastases. Similarly, contrast roentgenograms of the gastrointes¬ tinal tract, kidneys, or gallbladder are frequently nondiagnostic. At best they may suggest the presence and anatomic relationships of a retroperitoneal mass, but do not reveal the organ or tissue of origin. In a patient in whom the possibility of a tumor originat¬ ing in the inferior vena cava is suspected from history, tumor
or
by
physical, examination, roentgenograms, or findings at operation, the combined use of selective arteriography and vena cavography has the greatest likelihood of suggesting the correct diagnosis." In addition, the extent of involve¬ "1S
ment of the inferior
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vena cava
and tributaries such
as
the
renal and hepatic veins can be accurately assessed preoper¬ atively. If inferior vena cavography shows complete cavai obstruction, the proximal extent should be defined by introducing a catheter from above via an antecubital vein. MANAGEMENT
Optimal therapy of leiomyosarcoma of the inferior vena is surgical resection; primary treatment with either radiotherapy or chemotherapy usually offers little bene¬ fit."" Due to the difficulties of diagnosis, these tumors may have attained considerable size. However, it is important to recognize their characteristic slow growth and relatively low malignant potential. For these reasons, métastases are
cava
present in less than one-half of
cases at the time of may usually be dissected free of all neighboring structures excepting the vena cava itself. Direct invasion of local viscera is a late and infre¬ quent finding, and therefore aggressive surgery can often achieve local resection of tumors located beneath the hepatic veins.
diagnosis,
and the tumor
3. Operative photograph of middle segment of vena Proximal and distal occlusion has been obtained and vena cava has been opened after right kidney has been removed. Tumor nodularity is present within lumen of vena cava, extending into orifice of left renal vein (arrow).
Fig 3.—Case
cava.
mass
Specific points regarding surgical management depend largely on the segment of vena cava involved and the degree and duration of obstruction that exists. As discussed, much of this vital information can be obtained from preoperative arteriography and vena cavography.
Resection of the tumor mass in the lower segment and of the involved vena cava should be feasible. Interruption of the vena cava below the renal veins is well tolerated. Tumor growth at this level may be largely extraluminal, and large tumors may involve relatively small portions of the vena cava. If truly pedunculated, only a portion of the involved wall of the vena cava may require resection with the tumor mass, and closure primarily or with a patch may preserve the continuity of the vessel.1" However, since cavai interruption at this level is so well tolerated and local recurrence common, wide resection of the infrarenal vena cava would seem most prudent. Any associated venous thrombosis present in the iliac system should be removed, if possible, to minimize the chances of troublesome post¬ operative edema." Tumors at the middle segment of the vena cava currently present the most difficult management deci¬ sions, requiring careful planning and judgment. Formerly, interruption of the vena cava above the renal veins was believed to be almost uniformly fatal. However, there are an increasing number of case reports in which interruption at this level is indeed tolerated, including ligation for acute traumatic injury18·7'"'74 and ligation or resection at the time of right nephrectomy, usually for renal carcinoma with tumor extension to the vena cava."·79 By the time of diagnosis, most leiomyosarcomas of the vena cava will have produced significant venous obstruc¬ tion. The existence of established venous collateral circula¬ tion may be confirmed by preoperative vena cavography, and it offers assurance that the suprarenal vena cava may be interrupted without undue risk of severe hypotension from an acute reduction of venous return. It is important to monitor carefully the usual parameters of volume
with administration of adequate blood and colloid solutions, deleterious hemodynamic conse¬ quences may be prevented.74-28 Following interruption of the suprarenal vena cava, previous experience has indicated that the left kidney may be expected to function satisfactorily because of its unique collateral venous tributaries not present on the right. These have been well described by Anson and Cauldwell,"' and include adrenal, gonadal, and lumbar branches, which together richly communicate with the hemiazygos, paravertebral, and ascending lumbar systems. These collateral channels allow the left renal vein to be ligated centrally with expected preservation of adequate renal venous drainage and function, although a period of diminished function may occur.7' Again, any element of gradually developing venous obstruction will have enhanced these collateral systems, and less difficulty with function of the left kidney may be anticipated. Because of the anatomic lack of similar venous tribu¬ taries available to the right renal vein, it is most unlikely that function of the right kidney will be maintained following interruption of its venous drainage. It is inter¬ esting to note that in almost all reported survivors of ligation or resection of the suprarenal vena cava, a right nephrectomy was carried out simultaneously. Similarly, experimental work in dogs has revealed an increased survival when right nephrectomy was carried out with ligation of the suprarenal vena cava, as opposed to ligation without right nephrectomy.:il·32 Adequate surgical management of tumors involving the middle segment of vena cava will therefore involve wide resection of the vena cava, often from just below the hepatic veins to above the iliac bifurcation, with ligation of the renal veins at their point of entry into the vena cava. While the left kidney may be expected to survive and maintain renal function, especially when evidence of adequate collateral circulation has been demonstrated, the right kidney must be either removed or have its venous drainage reestablished. If function of the left kidney alone is suspect, one may inject indigo carmine dye.ls If dye appears in the urinary bladder within 10 to 15 minutes, one
replacement, and
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function of the left kidney is assured and that development of renal failure is unlikely. If the right kidney appears important to maintain renal function, autotransplantation to the right pelvis, employing stan¬ dard vascular techniques without division of the ureter,371 seems the most reasonable method, as was used in case 3 of this report. Results with prosthetic replacement of the vena cava or other venous segments have been almost uniformly discouraging, while other alternatives such as portorenal anastomosis seem unnecessarily complex.7'" Adequate exposure for tumors of the middle segment is best accomplished via a right-sided thoracoabdominal inci¬ sion carried through the bed of the eighth rib. The liver may then be reflected anteriorly by division of the trian¬ gular and coronary ligaments. When combined with reflec¬ tion of the duodenum and head of the pancreas, the entire vena cava from the main hepatic veins to the iliac bifurca¬ tion may be exposed. Several small accessory hepatic veins may be encountered and divided with impunity. Unfortunately, no satisfactory surgical treatment of tumors in the upper segment of the vena cava is possible at may
assume
the
present. Theoretically,
treatment
by hepatectomy,
resec¬
tion of the vena cava, and heterotopic autotransplantation of the liver might be achievable if the hepatic veins are uninvolved by tumor extension or secondary thrombosis." Because of the propensity of these tumors to recur locally, the adjunctive use of postoperative radiotherapy to the tumor bed following surgical resection of lesions of the lower or middle segments of the vena cava seems reason¬ able. At least one report has shown radiotherapy to be helpful in the palliative management of established local recurrence.'4
Leiomyosarcoma rare
of the inferior
vena cava
remains
a
lesion, but it is being reported with increasing
frequency. Its slow growth and relatively low malignant potential offer the chance for cure or long-term palliation for those tumors below the hepatic veins. The use of preoperative angiography and vena cavography, together with modern vascular surgical and anesthetic techniques, should allow increased salvage of these difficult problems. Nonproprietary Name and Trademark of Drug Doxorubicin
hydroch\oride-Adriamycin. References
1. Kevorkian
J, Cento DP: Leiomyosarcoma of large arteries and veins.
Surgery 73:390-400,
1973. 2. Perl L: Ein fall von sarkom der vena cava inferior. Virchows Arch Pathol Anat 53:378-383, 1871. 3. Landes E: Leiomyosarcoma of the inferior vena cava. Dapim Refuiim 24:453-456, 1965. 4. Deutsch V, Fraenkel O, Frand V, et al: Leiomyosarcoma of the inferior
vena cava
propagating into the right
atrium. Br Heart J 30:571-574, 1968.
BS, McGill DAF, Williams R: Leiomyosarcoma of inferior vena cava producing Budd-Chiari Syndrome. J Pathol 104:283-286, 1971. 6. Wray RC, Dawkins H: Primary smooth muscle tumors of the inferior vena cava. Ann Surg 174:1009-1018, 1971. 7. Johansen JK, Nielsen R: Leiomyosarcoma of the inferior vena cava: Report of a case. Acta Chir Scand 137:181-184, 1971. 8. Justiniani FR, Cohen GH, Roen SA, et al: Budd-Chiari Syndrome due to leiomyosarcoma of the inferior vena cave. Am J Dig Dis 18:337-346, 5. Cardell
1973. 9. Couinaud C: Tumeurs de la veine cave inferieure. J Chir 105:411-432, 1973. 10. Stuart FP, Baker WH: Palliative surgery for leiomyosarcoma of the inferior vena cava. Ann Surg 177:237-239, 1973. 11. Kapsinow R, Brierre JT: Leiomyosarcoma of the inferior vena cava. J La State Med Soc 126:400-401, 1974. 12. DeMoulin JC, Sambon Y, Bandinet V, et al: Leiomyosarcoma of the inferior vena cava: An unusual cause of pulmonary embolism. Chest 66:597\x=req-\ 599, 1974. 13. Missal ME, Robinson JA, Tatum RW: Inferior vena cava obstruction: Clinical manifestations, diagnostic methods, and related problems. Ann Intern Med 62:133-161, 1965. 14. Jurayj MN, Midell AI, Bederman S, et al: Primary leiomyosarcomas of the inferior vena cava. Cancer 26:1349-1353, 1970. 15. Nartowicz E, Domaniewski J, Wiecko W: Leiomyosarcoma de la veine cava inferieure: Traitment errone de cholecystite. Maroc Med 47:339-340, 1967. 16. Guedon J, Mesnard J, Poison J, et al: Hypertension r\l=e'\no-vasculaire par leiomyosarcome de la veine cave inf\l=e'\rieure.Ann Med Interne 121:905\x=req-\ 912, 1970. 17. Hoffbrand AU, Lloyd-Thomas HG: Leiomyosarcoma of the inferior vena cava leading to obstruction of the tricuspid valve. Br Heart J 26:709\x=req-\ 714, 1964. 18. Caplan BB, Halasz NA, Bloomer WE: Resection and ligation of the suprarenal inferior vena cava. J Urol 92:25-29, 1964. 19. Stanley CJ, Valaitis J, Trippel OH, et al: Leiomyosarcoma of the inferior vena cava. Am J Surg 113:211-216, 1967. 20. Mehta AR, Rajpal RM, Jussawalla DJ: Suprarenal ligation of the inferior vena cava with a solitary horseshow kidney. Am J Surg 116:925-928, 1968. 21. Ramnath R, Walden EC, Caguin F: Ligation of the suprarenal vena cava and right nephrectomy with complete recovery. Am J Surg 112:88-90, 1966. 22. Waltuck TL, Crow RW, Humphrey LJ, et al: Avulsion injuries of the vena cava following blunt abdominal trauma. Ann Surg 171:67-72, 1970. 23. Bolot F, Germain J, Ponsan R, et al: Blessure par bulle de la veine cava inferieure au dessus des pedicules renaux. Mem Acad Chir 81:394-398, 1955. 24. Gazzaniga AB, Colodny AH: Long-term survival after acute ligation of the vena cava above the renal veins. Ann Surg 175:563-568, 1972. 25. McCullough DL, Gittes RF: Ligation of the renal vein in the solitary kidney: Effects on renal function. J Urol 113:295-298, 1975. 26. Skinner DG, Pfister RF, Calvin R: Extension of renal cell carcinoma into the vena cava: The rationale for aggressive surgical management. J Urol 107:711-715, 1972. 27. Clark CD: Survival after excision of a kidney, segmental resection of the vena cava, and division of the opposite renal vein. Lancet 2:1015-1018, 1961. 28. Pathak IC: Survival after right nephrectomy, excision of infrahepatic vena cava, and ligation of left renal vein: A case report. J Urol 106:599-602, 1971. 29. Duckett JW, Lifland JH, Peters PC: Resection of the inferior vena cava for adjacent malignant diseases. Surg Gynecol Obstet 136:711-716, 1973. 30. Anson BJ, Cauldwell EW: The pararenal vascular system. Q Bull Northwestern Univ Med School 21:320-328, 1947. 31. Sapirstein LA, Reininger EJ: Catheter-induced error in hepatic venous sampling. Circ Res 4:493-496, 1956. 32. Lespinasse V: Ligation of the vena cava above the renal veins with or without nephrectomy. Q Bull Northwestern Univ Med School 21:312-316, 1947. 33. Corman JL, Anderson JT, Taubman J, et al: Ex vivo perfusion, angiography and autotransplantation procedures for kidney salvage. Surg Gynecol Obstet 137:659-665, 1973. 34. Allan J, Burnett W, Lee FD: Leiomyosarcoma of the inferior vena cava. Scott Med J 9:352-355, 1964.
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