RESECTION OF THE AXILLARY VEIN IN RADICAL MASTECTOMY: ITS RELATION TO THE

MECHANISM OF LYMPHEDEMA IAN MACDONALD, M.D.

E V I D E N C E to be offered in this com- munication will indicate the frequent neces- sity for axillary-vein resection in the operative treatment of mammary carcinoma and will also suggest the possibility of eventually in- cluding this anatomical extension of radical mastectomy as a routine measure. The abso- lute indication for axillary-vein resection should be the presence of apparent lymph- node metastases attached, or in close prox- imity, to the sheath of the vessel. Resection of the vein in such instances provides a real approach to the adequate en-bloc dissection of the axillary space. Its inclusion as a rou- tine step should be equally as desirable, if it can be shown that the postoperative sequelae, particularly lymphedema of the homolateral extremity, are no greater, or even less severe, than those of the conventional procedure. The early results in a small group of patients, reported herewith, constitute tentative con- firmation of the latter possibility. The dimin- ished degree of lymphedema consequent upon axillary-vein resection will be discussed in terms of the possible mechanism of its pro- duction.

Neuhof, in I 938, reported eleven patients in whom he had resected the axillary vein in the presence of adherent lymph-node metas- tases. Two of these women had “some” lymphedema, two had fluctuating edema of the hand, the others were reported as having developed no lymphedema. In 1932, nine cases that had had resection of the axillary vein were reported by Costantini, who ob- served immediate, transient edema in some patients but concluded that the late results were as good as, or better than, in those with conservation of the vein. Costantini suggested

From the Department of Surgery, School of Medicine, University of Southern California, Los Angeles, Calif.

Received for publication, August I I , 1948.

that a lesser degree of edema might be ex- pected because of the sympathectomy accom- plished by resection of the vein.

A review of the literature since 1925 re- vealed no other definitive information, al- though several authors refer to the desira- bility of vein resection in cases with extensive nodal involvement and report no unusual subsequent swelling of the arm. One of these, Treves, observed that the axillary vein may be resected with no more than transient edema and that of a soft, nonbrawny type.

ETIOLOGY

A number of writers, headed by no less an authority than Halsted, have advanced the belief that the lymphedema is caused by a lymphangitis secondary to the low-grade in- fection that is associated with the necrosis of the skin edges and the adjacent cellulitis in so extensive an operative area. The end re- sult may be a sclerosis of the lymphatics, the extent and severity of which determines the degree of lymphedema. In some instances, a recurrent, acute or subacute inflammatory process may appear in the arm, or even in the forearm, accompanied by an increased degree of lymphedema. The writer has ob- served such a process as late as four years after mastectomy; it had the physical charac- teristics of an acute lymphangitis and re- sponded promptly to the use of antibiotics. The bacteriological agent most likely to be present is a streptococcal invader. Again, obesity is commonly recognized as a predis- posing factor in postmastectomy edema and, further, increasing degrees of adiposity in- crease the likelihood of edema. I t seems logical that this tendency is due to more ex- tensive areas of fat necrosis in the operative field in the obese patient, establishing favor- able conditions for regional cellulitis.

AXILLARY : VEIN RESECTION AND POSTMASTECTOMY LYMPHEDEMA Macdonald [6 19

FIG. I . Lymphatics of the upper extremity (I’oldt: Atlas of A n a t o m y ) .

There is now almost complete agreement that postmastectomy swelling of the upper extremity is due to lymphatic obstruction and probably is not directly dependent upon venous destruction or resection. Relevant evi- dence of some value may be derived from certain anatomical observations in lymph- edema that develops in thrombophlebitis of the upper extremity. The axillary vein ex- hibits a profuse encircling arrangement of

perivenous lymphatics, and the edema of the arm associated with axillary phlebitis is pre- dominantly a lymphedema due to lymphan- gitis with obstructive effect. Here, as in the lower extremity, the end result may be a per- manent lymphedema from lymphatic sclero- sis. There is also other evidence indicating the importance of perivenous lymphatic involve- ment in the early development of edema as- sociated with thrombophlebitis. Thus, the ob-

CANCER November 1948 6201

FIG. 2. Section of the axillary vein showing abundant periuenous lympha- tic channe2s.

servations made by Stewart and Treves in postmastectomy lymphedema with lymphan- giosarcoma suggest that a perivenous axillary lymphangiectasia was frequent and that peri- venous lymphangiomatosis is of special im- portance in the determination of the original sites of the changes leading to this extraordi- nary neoplasm.

Some degree of lymphedema invariably oc- curs following a radical axillary dissection. In half or more of -the patients, it is of little importance and, in many, may be unobserved on casual inspection. The area of invariable involvement, and the only area in those pa- tients with “no edema” on casual examina- tion, is the anteromedial portion of the upper and middle third of the corresponding arm. Minor lymphedema in this area is most evi- dent on posturing the extremity in go-degree abduction with the elbows flexed and com- paring it with the opposite extremity. In sev- eral patients studied by Berne and the au- thor, intracutaneous dye was injected into the skin over the anteromedial portions of the arm on the evening prior to radical mastec- tomy. In each instance, at operation, the dye was most evident in lymphatics located on the lateral axillary wall, while minute amounts of dye were seen spreading in ar- borescent fashion toward the axillary vein. This invariable minimum postoperative lymphedema is the evident sequel of sur- gical resection of the lymphatic system dur-

ing axillary dissection, and such postextirpa- tive swelling will be limited to the tributary, anteromedial portion of the arm. In favor- able instances, the remainder of the arm has adequate lymphatic drainage through col- lateral and uninterrupted channels.

Although the several groups of axillary lymph nodes constitute the major afferent destination of the lymphatic drainage of hand, forearm, and arm, there are some pathways not included in the operative field of axillary dissection. Most of the superficial lymphatic vessels of the arm, anteriorly, bend medially in the mid-third and pursue a some- what oblique course along the anteromedial portion of the upper third to drain into the central axillary group of nodes. One or more channels usually divert from this path and ascend the arm in company with the cephalic vein and thus reach the supraclavicular nodes. Still additional lymphatic drainage is present posteriorly, along the posterior cir- cumflex vessels and along suprascapular routes to posterior cervical nodes. Diversion of the lymphatic drainage through these routes accounts for the minimum lymph- edema present after extirpation of the axil- lary lymph system. In some instances of moderate edema without evident postopera- tive infection, the anatomical insufficiency of such collateral routes may well be a reason for the increased swelling, but the number occurring on such a basis is probably small.

After radical mastectomy, 40 to 5 0 per cent of women have moderate or severe lymphedema, not due to recurrent disease. In approximately 2 per cent, the process be- comes advanced enough to deserve the desig- nation of postoperative elephantiasis and can become so crippling as to require disarticula- tion of the extremity.

There is a justifiable uncertainty about how accurate a knowledge surgeons have of the incidence and degree of postmastectomy lymphedema. The writer encountered a dearth of information, both in his own and in out-patient follow-up records, concerning the absence, presence, or degree of post- operative swelling of the arm. It was possible to obtain accurate information on forty un- selected private patients who had had radical

AXILLARY: VEIN RESECTION AND POSTMASTECTOMY LYMPHEDEMA Macdonald [62 I

FIG. 3 . Additional tissue removed in one patient by resecting the axillary vein after completion of the conventional procedure. Axillary vein held taut between trero hemostats.

TABLE I

POSTMASTECTOMY LYMPHEDEMA IN 40

VEIN RESECTION PATIENTS WITHOUT AXILLARY-

Lymphedema

“None” Min. Mod . Severe

Incidence ...... 2 I3 23 2

Axillary-node involvement

.... 0 Stage I 2 5 5 Stage I1 ... o 8 18 2

Prompt 2 I 1 3 I Delayed ... o 2 20 I

Thin 2 7 Average ... o 6 15 0 Obese ..... o 0 7 2

Healing ....

Body weight ...... I 0

mastectomy without vein resection during the past several years. The status of these women is shown in Table I ; they serve as a reason- able control group because of accurate evalu- ation rather than by their numerical weight. “No” edema is that detected only by careful examination as already described, while “minimum” edema is limited to the upper portion of the arm (although it is usually also present in the anteromedial portion) and is not of subjective importance. “Moderate” indicates more extensive swelling of part or all of the arm, frequently with fluctuating edema of the adjacent portion of the fore- arm. There is little or no impairment of func- tion, but frequently it is the source of dis-

6221 CANCER November 1948

comfort to the patient. “Severe” swelling of the arm is that in which the edema extends tr, the forearm and usually the dorsum of the hand, and produces gross enlargement and disturbance of function. By this arbitrary di- vision, an unexpectedly large proportion of these forty patients exhibited more than minimum edema. It is probable, however, that the clinician’s concept of this problem is usually based on the number of women who

Most impressive is the relation of obesity to postoperative lymphedema (Table I ) . De- spite the small number of patients, the weighted incidence of increasing edema with increased relative body weight constitutes re- liable evidence that obesity is the most im- portant single factor contributing to lymph- edema. It was further noted in these patients that all of the obese patients had some degree of delay in wound healing, supporting the

FIG. 4. Patient E.S., ten days following axillary-vein resection.

complain of swelling rather than on objective recording of its presence.

Table I also shows the degree of postopera- tive lymphedema according to the absence or presence of axillary-node metastases. Al- though there seems to be a slight excess of edema in those with nodal metastases, this may be associated with the tendency to do a more radical procedure in such patients. It is noteworthy that in the patients with lymphangiosarcoma reported by Stewart and Treves, all of whom had severe lymphedema, none of the three in whom microscopic evi- dence was available had nodal metastases.

The relation of wound healing to subse- quent lymphedema for the forty patients is presented in Table I . Here the evidence indi- cates delayed healing to be a distinct factor in the production of lymphatic obstruction.

previously suggested chain of events - fat necrosis, secondary infection, and regional lymphangitis terminating in lymphatic ob- struction. As has been suggested by Berne, the mechanical derangement of the lymphatic system in obesity may also be an important factor in the development of postoperative lymphedema : with deep layers of panniculus, the superficial and deep lymphatics become widely separated, the communicating chan- nels are greatly stretched and thinned, and the reserve capacity of the accessory routes of drainage is severely impaired.

Since 1944, fifteen patients have had an axillary vein resection with radical mastec- tomy (Table 2). Technically, this extension of the conventional procedure permits a thorough en-bloc dissection of the axilla, not possible if the axillary vein is conserved. The

AXILLARY: VEIN RESECTION AND POSTMASTECTOMY LYMPHEDEMA Mncdonald [623

FIG. 5. R.S.S., four years following axillary-vein resection.

TABLE 2

AXILLARY-VEIN RESECTION IN RADICAL MASTECTOMY

Date of Venous Lymph- Initials Operation Axillary Nodes Obstruction edema Present Status

P.D.

R.S.S. L.C. R.N.

L.W. E.B.

C.G. B.M.

J.S.

D.L. M.M. E.S. M.G. J.R. M.P.

9- 15-44

12- 19-44 2-28-46 4- 5-46

6- 7-46 I 1-23-46

2- 14-47 4- 5-47

4-28-47

4- 3-47 4- 3-48 4- 17-40 4-1 7-48 6- I 2-48 7- 1-48

?

Negative Mult. metastases Positive

Negative Diffuse metastases adherent to vein

Negative Positive (extensive) Positive (extensive) Negative Positive Negative Negative Positive Mult. adher. to vein

None

None Partial None

None None

None Partial

None

None None None None None None

Minimum

“None” Minimum Minimum

“None” No imme- diate

Minimum Minimum

Moderate

“None” “None” Minimum Moderate Moderate Minimum

Died, 8 mos. p.0.; metastases N.E.D. N.E.D.

after 2 mos. p.0. N.E.D. Died, 6 mos. p.o., with edema of arm due to extensive local recurr. N.E.D. Died, I I mos, p.0; metastases N.E.D.

Well Well Well Well Well Recent postoperative

NO follow-up

6241 CANCER November 1948

cephalic vein has been preserved in each in- stance. The increase in the extirpative prod- uct of axillary dissection is so impressive as to make one believe that the classical Halsted operation is an incomplete procedure. Of local postoperative recurrences, 5 to 7 per cent are axillary, so that the increased effective- ness of the dissection ensuing on vein resec- tion should materially reduce this incidence. From a theoretical standpoint, it is entirely possible that some increased salvage may also result from resection of perivenous lymphat- ics, not ordinarily removed, in which meta- static emboli represent the most remote line of advance at the time of operation. Such a single metastasis within a lymphatic channel was so located in one of five cases in serial blocks taken from the axillary vein and re- trovenous tissues.

The present status of lymphedema in these fifteen patients with postoperative intervals varying from three months to four years, is indicated in Table 3. These results are suffi-

TABLE 3 LYMPHEDEMA IN 15 PATIENTS WITH

AXILLARY-VEIN RESECTION

“None” 5 Minimum 7 Moderate 3 Severe 0

cient to provide assurance that resection of the axillary vein provides no additional haz- ard to the patient and, in fact, offers some promise of diminished degrees of edema. The theoretical basis, which lends validity to this possibility, is that removal of the lymphatic channels surrounding the vein eliminates the primary site of secondary postoperative in- fection in the lymphatic system, with the cor- ollary assumption that the lymphangitic proc- ess usually has its origin in the apical, peri- venous lymphatics, the integrity of which has been prejudiced by the axillary dissection.

Conservation of the vein inevitably leaves many open stumps of lymphatic vessels, through which infection readily gains access to the perivenous lymphatic bed. Treves has emphasized postoperative cellulitis and the production of a bandlike sclerosis over the medial portion of the axillary vein, but the importance of this sclerosing process must lie in the production of lymphatic obstruction. The last six of these patients have had pro- phylactic postoperative penicillin.

While the present series is too limited in number and elapsed time to constitute more than tentative evidence, the writer has adopted a policy of routine resection of the axillary vein in the presence of apparent ax- illary lymphnodal metastases.

CONCLUSIONS

I . The sequel of events leading to post- mastectomy lymphedema are fat necrosis in the operative field, secondary infection, re- gional (perivenous) axillary lymphangitis with sclerosis, and obstruction. Obesity is the most important, single predisposing factor in the genesis of lymphedema.

2. The frequency and degree of postopera- tive lymphedema of the upper extremity have been distinctly decreased in fifteen pa- tients, compared to a carefully evaluated con- trol group of forty patients subjected to radi- cal mastectomy with conservation of the axil- lary vein.

3. Resection of the axillary vein permits an adequate en-bloc dissection of the apical portion of the axilla. The extirpative exten- sion thus achieved makes the classical opera- tion appear incomplete.

4. Evidence is offered to indicate that axil- lary-vein resection eliminates that portion of the surgically altered, axillary lymphatic sys- tem in which the secondary inflammatory process commonly originates.

REFERENCES COSTANTINI, H . : Peut-on rtsequer la veine axillaire dans le traitement du cancer du sein? Bull. st

* NEUHOF, H.: Excision of the axillary vein in the radical operation for carcinoma of the breast. Ann.

‘ROUVIBRE, H.: Anatomy of the Human Lymphatic System. (Trans]. by M. J. Tobias.) Ann Arbor.

‘TREVES, N . : The management of the swollen arm in carcinoma of the breast. Am. 1. Cancer 15:

STEWART, F. W., and TREVES, N.: Lymphangiosarcorna in postmastectorny lymphedema. Cancer I :

mim. SOC. nut. de chir. 58: 1284-1286, 1932.

Surg. 108: 15-20, 1938.

Edwards Bros. 1938.

271-276, 1931.

64-81, 1948.