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Tumor-Thrombosis of the Inferior Vena

Cava

With Four Additional Cases of Neoplastic Invasion' BY WALTER M. SIMPSON, Instructor in Pathology, University of

O

Michigan, Ann Arbor, Michigan

BSTRUCTION of the inferior instances in which there is neoplastic
vena cava occurs SO fre- invasion of the lumen of the vein as
"Geschwulstthrombose."
In every
case of penetration of the intima of
the vein wall by new growth or of
invasion by extension through a
tributary, the mass of invading cells
is treated as a foreign-body, and a
mural thrombus results from the
agglutination and precipitation of the
blood elements at the point of invasion,
followed by coagulation. The result-
ing thrombus offers a favorable en-
vironment for the rapid growth of
the neoplasm cells, and if the process
is sufficiently protracted, obturation
will ultimately result. Even though
the neoplasm cells per se may com-
pletely occlude the lumen, there is
always superinduced thrombosis
above and below the new growth.
Because of this inevitable association
between neoplastic invasion and the
simultaneous deposition of fibrin upon
the invading cells, and because of the
fact that the tumor cells from the start
constitute an integral part of the
thrombus, the term "tumor-throm-
bus" is used in this paper.

quently that it cannot be considered a pathological rarity. Three cases have appeared at the University of Michigan Hospital during the past year. Pleasants (no. 20), in a masterly monograph published in 1911, brought together 296 cases, to which he added 18 cases studied by himself, bringing the total to 314. In 50 of these, 16 per cent of the entire number, obstruction of the inferior vena cava was due to neoplastic invasion of the lumen. It is with this type of obstruction, tumor-thrombosis, that the present paper is chiefly concerned. A diligent search of the literature has added 24 cases to those collected by Pleasants, most of them reported since 1911. Four cases are now added from this laboratory, making a total of 78.

The term "tumor-thrombosis" is not used to any extent in the English or French literature, but the German writers have long referred to those

From the Pathological Laboratory of the University of Michigan, Ann Arbor, Michigan.

2 Numerals prefixed with "no." refer to number of case in the tabulated résumé at end of paper. All other numerals refer to list of literature references.

Direct extension of the neoplasm to the inferior vena cava through a tributary is much more common than actual penetration of the wall of the

vena cava from the outside. This is particularly true in invasion from renal and testicular neoplasms. The renal and spermatic veins are frequently filled with cylinders of new growth which extend as continuous cords of tumor cells into the inferior vena cava. The growth in the vena cava is at first influenced by the direction of the blood stream and is almost invariably upward. After this influence is lost by a complete interruption to the upward flow of blood, there may be downward extension. In at least

neo

cases the intravascular growth extended even into the right auricle, filling it to a greater or less degree. In 6 cases, the continuous growth entered the tricuspid orifice, and produced mechanical interference with the action of the tricuspid valve. Breus (no. 33) has reported the most. marked instance of extensive plastic invasion. A malignant teratoma testis extended the entire length of the right spermatic vein, completely filled the inferior vena cava, and grew into the right auricle and ventricle, which were nearly entirely filled. There was further extension through a patent foramen ovale into the left cardiac chambers.

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century than is the case now. This requires explanation, and it is the writer's belief that the finding of the superficial venous dilatation was a stimulus for autopsy investigation of the cause in the days when autopsies were less frequently done as routine. procedure. The great majority of the more recently reported cases were accidental discoveries at the necropsy table. Thus we see that in the 18 cases in the Johns Hopkins Series reported by Pleasants, 14 came to autopsy without a diagnosis of vena caval obstruction. Of 15 cases observed in the Mayo clinic (no. 11), only one was recognized before death. In not one of the 4 cases in our series was obstruction thought of during life. Of the 58 cases in which clinical data was given, only 28, or less than onehalf, showed the important diagnostic sign sine qua non-the superficial collateral circulation. The reason for this failure of diagnosis is at once apparent.

There are other cases in which the deep channels alone, principally the ascending lumbar-azygos and hemiazygos superior vena cava route, establish circulatory equilibrium and no superficial signs are presented, save perhaps a more or less transient edema of the legs. The same lack of superficial evidence has likewise been repeatedly noted in non-neoplastic obstruction. Meyer (1) reported a case of complete atresia, probably congenital, of portions of both the superior and inferior venae cavae in a man of eighteen years. Postmortem study indicated that a considerably dilated vena azygos major gave almost complete compensation by way of the patent lower superior vena cava.

Hallett (2) described a case in which the lower inferior vena cava was a slender fibrous cord. The collateral circulation was entirely limited to the deep channels. Peacock (3) and Fahrner (4) have reported cases in which there was no superficial collateral circulation, but autopsy revealed the establishment of deep compensatory routes which were quite sufficient to insure adequate venous return of the blood from the lower half of the body.

There is an abundance of experimental and clinical evidence to indicate the ease with which the circulatory apparatus can quickly adapt itself to either sudden or gradual complete obstruction of the inferior vena cava. There was a belief among the older writers that there must be a slowly progressive closure of the vena cava in order to allow gradual establishment of collaterals, and that any sudden interruption would be incompatible with life. Recent investigation indicates that such generalities are not entirely justified. The point at which rapid occlusion occurs determines the ease or difficulty with which compensation is obtained. After extensive experimentation with dogs, Béjan and Cohn (5) found that ligation of the inferior vena cava below the renal veins, or at a point just above the renal veins and including the left suprarenal vein in the ligature, was well tolerated and entirely compatible with good health. In those instances in which the renal veins were obstructed, the circulation was reestablished by the compensatory dilatation of the capsular veins at the superior poles of the kidneys which communicate directly with the suprarenal, diaphragmatic, lumbar and azy

gos veins. Picard (6) ligated the inferior vena cava in animals at a point between the liver and the right auricle and produced death in every instance within four hours.

There are many cases on record in which the inferior vena cava has been ligated in man, following injury to the vein during surgical manipulation. Béjan and Cohn (5) reported a case in which the inferior vena cava was severely lacerated during the removal of a massive abdominal sarcoma. Large clamps were placed above and below the tear, followed by ligation. The patient was in good condition at the end of the operation and survived with no other difficulty than a slight transient edema of the right leg. Housel (7) also ligated below the renal veins with no resultant edema or superficial phlebectasis during the year that the patient was under close observation. Cole (8) tore the inferior vena cava while separating firm adhesions between a retroperitoneal tumor mass and the vena cava. Profuse hemorrhage followed. The vein was clamped below the laceration and compressed above with a sponge, while the tears were sutured. The operator was entirely disappointed in his anticipations of vascular disturbances, a transient edema of the right leg being the only sequel.

Marconi (9) told of a case in which a segment of the lower inferior vena cava several centimeters long was resected after injury which resulted during the removal of a prevertebral lymphosarcoma. There was complete recovery with only moderate temporary edema. Heresco (10) and Hartmann (11) accidentally injured the inferior vena cava during operation

and ligated it below the renal veins. Recovery was prompt and without edema or any other evidence of circulatory upset. Delaunay (12) ligated 3 cm. below the renal veins in a woman of forty-eight, following injury received during the removal of a renal tumor. Edema of the right leg and a superficial collateral circulation developed and menses ceased. In eight months, both the edema and superficial collaterals were gone and regular menstruation was reëstablished.

This absence of signs of serious vascular upset in such cases of complete and sudden obstruction is probably to be explained by the multiplicity of small collateral channels, all of which are capable of sudden slight dilatation, the sum total of which is sufficient to establish rapid compensation. The period of adjustment is indicated by the transient edema. The laxness of the abdominal wall is another factor which aids in prompt reëstablishment of the return circulation. Proof of this lies in the mildness of the circulatory disturbances in obstruction of the inferior vena cava as contrasted with the serious symptoms which result from obstruction of the superior vena cava, in which the rigidity of the bony thoracic wall, particularly of the superior thoracic strait, prevents the necessary degree of expansion.

DIAGNOSIS

The most dependable diagnostic criteria are (a) edema of the legs, followed by (b) antero-lateral abdominal and thoracic phlebectasis. Pain, usually abdominal or lumbar, is a frequent initial onset symptom. Its relation to the caval obstruction is

difficult to evaluate because the pain may well be due to the extravascular malignant growth. It is not a characteristic pain and in itself lends little to the diagnosis. The clinical manifestations of obstruction of the inferior vena cava vary somewhat with the location and extent of the obstructing thrombus. In the inferior one-third (below the renal veins) complete obstruction, either sudden or gradual, may give no external evidences. Edema, if present, may be due to extension of the thrombus into the iliac veins or to concomitant myocardial or renal insufficiency. The superficial collateral circulation, when present, is the chief aid to diagnosis. The superficial veins in the groin are usually the first to show dilatation. The veins over the antero-lateral abdominal and thoracic walls next undergo gradual enlargement. The collaterals, particularly of the abdomen, often reach the size of the little finger. The veins chiefly involved are the superficial inferior epigastric below, communicating with the internal mammary above, and the superficial iliac circumflex below anastomosing with the superficial long thoracic above. It is not uncommon to find that the edema of the lower extremities abates as the supplementary circulation is established. The direction of the blood flow is upward in the distended abdominal veins. The venous dilatation is frequently accentuated by upright posture. Edema of the external genitals is not uncommon when the right spermatic vein is blocked. Albuminuria is a rare finding in obstruction involving only the lower one-third.

In the middle one-third, or renal portion, obstruction frequently leads.

to disturbed renal function with albuminuria and occasionally hematuria. This is, however, usually of short duration because of the ease with which the renal capsular collaterals reëstablish circulatory balance. There are many cases of obliterating thrombosis above the renal veins with no albuminuria at any time.

In the upper one-third, or hepatic portion, the signs of hepatic and portal obstruction may appear, giving an enlarged liver, spleen, gastro-intestinal disturbances due to stasis catarrh, ascites and jaundice (Chiari's disease). These cases are usually diagnosed as hepatic cirrhosis or Banti's disease. In most of these cases the renal portion is blocked also, so that albuminuria may be present. Edema of the abdominal wall, as well as both lower extremities, is not uncommon in obstruction of the upper two-thirds.

In cases where there is evidence of abdominal malignancy, with more or less sudden development of a progressive edema of the lower extremities it is well to consider obstruction of the inferior vena cava. The absence of the signs of a myocardial or renal inadequacy sufficient to account for the edema will lend support to the diagnosis. The sudden enlargement of the liver with or without the development of ascites, in a person presenting signs of obstruction of the inferior vena cava, points to an upward extension of the obturating thrombus into the hepatic portion. The detachment of a large fragment from the upper part of the tumor-thrombus occasionally causes sudden death from pulmonary embolism.

Schlesinger (13) and Phillips (14) have emphasized the frequency with

which persistent unilateral edema. occurs in vena caval obstruction. It is probable that in these instances the thrombosis began in the iliacs, with the early establishment of good compensation on one side.

PATHOLOGY

Renal group

Of the new growths which give rise to tumor-thrombosis of the inferior vena cava, those arising in the kidney are the most common and important. In these cases there is almost invariably a direct extension of the malignant growth through the renal vein with gradual propagation by continuity into the lumen of the inferior vena cava. Of the 65 cases included in this study in which the primary source of the neoplasm was known, 32 (50 per cent) were due to invasion from renal neoplasms. Any attempt to divide these into carcinoma or sarcoma is at once destined to failure, because many of the earlier writers referred to the new growths as "cancerous or encephaloid masses" or as "pultaceous material identical with that of the renal cancer." In all probability many of the earlier "cancers" and "mixed neoplasms," as well as many of the ill-defined carcinomas and sarcomas and hypernephromas of more recent description are to be interpreted, in the light of our present knowledge, as malignant teratomas. Consequently, in the résumé which concludes this paper, the original diagnosis is stated, with no attempt at further classification.

It is in this group and in the testicular group that we observe the most extensive invasions. In many instances

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