An evaluation of the etiological factors of lymphedema following radical mastectomy. An analysis of 1,007 cases

AN EVALUATION OF THE ETIOLOGICAL FACTORS OF LYMPHEDEMA

FOLLOIVIN G RADICAL M ASTECTO MY Ara Analysis of 1,007 Cases

NORMAN TREVES, M.D.

HE probleni of the swollen arm that may T follow radical mastectomy is of much more than academic interest, Certainly to the in- dividual with such a complication it is of primary-and ol ten solitary-concern. Aside from body disfigurement and chronic and acute pain, the psychic insult may be most difficult to compensate and may constitute a problem that is as insoluble as the physical one.

All patients suffering from lymphedema of the arm are therapeutic problems, whether the condition is produced by recurrent or by primary inoperable cancer. The complication seem5 paradoxical and untimely when surgery has produced a satisfactory arrest of the breast cancer and then this persistently painful and disfiguring sequel ensues.

Oncc the swollen arm has appeared, therapy has often, unlortuna tely, proved only tran- siently bencficial or entirely disappointing. Various physiotherapeutic measures based on posture, cxercise, massage, or bandaging may give temporary relid or, at least €or a while, minimize discomfort. Unless an inoperable recurrence develops or there is fibrosis resulting from operation, infertion, or roen tgen-ray therapy, surgical procedures may be attempted to reduce the swelling. But the large number of procedures devised to correct this complication indicate only too forcefully how unsatis- factory they usually are. It is possible that the use of the gelfoam roll, which has proved use- ful in prophylaxis, may also prove practical for trea tmcnt.43

Beyond this brief summary we do not intend to discuss the various procedures developed for the relief oE the swollen arm. Nor will we discuss prophylactic measures except insofar as

From the Breast Scrvice, Department of Surgery, Memorial Center for Cancer and Allied Diseases, New York, New York.

Based in part upon a paper given before the Fifth Annual Cancer Symposium of the James Ewing So- ciety, March 7, 1952.

Received for publication April 17, 1957.

our review of the literature and analysis of our own cases may suggest factors whose consideration may contribute to the development of specific measures of prevention. Finally, we are not intending to re-emphasize the fact that un- complicated brawny edema may be followed by a totally different malignant lesion appear- ing in these arm5 long after the arrest of brcast cancer.

Our primary purpose is to present evidence concerning factors of possible causative significance as disclosed by analysis of the cascs of postmastectomy swollen arm seen at Memorial Hospital between 1939 and 1943. This period was chosen because the previously routine postoperative radiation therapy was being cur- tailed to a degree that made it possible to compare results for patients who had and had not received such treatment. Surgical therapy during this period was carried out in a routine manner by the resident staff, which eliminated variations in results owing to differences in operative methods. Also sufficient time-more than ten years-has elapsed to permit adequate follow-up, a €actor that is especially important in studying a complication that is notoriously irregular as to time of appearance and course.

DEFINITION or; SWOLLEN ARM

Ry the nonedematous arm is nwant one in which neither the patient nor the surgeon can dectect a difference in si7e greater than could be accounted for by normal variations.

In 1921, Halstedl6 suggested the term “elephantiasis chirurgica” to describe the swollen arm that iollows radical mastectomy. Since he quoted hfatas a t length, i t seems likely that this term was derived from Matas’26 definition, written in 1913: “By elephantiasis we mean a progressive histopathalogic state or condition which is characterized by a chronic inflammatory fihromatosis or hypertrophy of the hypodermal and dermal connective tissue which is preceded by and associated with lym-

444

so. 3 LE,MPHEDEMA AFTER RADICAL MASTECTOMY * Treues 445

phatic and venous stasis, and inay be caused by any obstruction or mechanical interference with the return flow of the lyniphatic and 5 enous currents. . . .” Matas stated further that lyinphatic and venous stasis were sufficient to cause edema but wcre not adequate alone to cause the fibrornatous characteris tic ol elephantiasis.

A definition of lymphedema has recently been published by the Criteria Committee of the Sew York Heart Association, composed ol a group of cardiologists under the chairman. ship of Pardee.3 This committee proposcd the follow in g :

Lymphedema refers to edcma resulting from obstruction of the lymphatic flow. Microscop- ically, the early changes consist of dilatation of the lymphatics and widening of the tissue spaces due to edema. In long-standing lymphe- denia there is proliferation of the connective tissue, often a variable degree of inflammatory cell infiltration, pigmentation, and fibrotic thickening of the dilated lymphatics. Clini- cally, the changes can he correlated with the fact that at first the edematous tissue is com- pressible (“soft edrma”), but later the swollen tissue is firm (so-called “brawny induration” or “hard edema”). I t is characteristically pale, in contrast to the cyanosis or rubor seen with vcnous stasis. The term “elephantiasis” is used lor the giotesque deformities of the more severe type.

INCIDE NCI. OF SWOLLEN ARM

Different in1 estigatms record and define both swelling and degrees of swelling in such widely varied terms that inevitably estimates of incidence are strikingly differmt. Besides, dates of reports cover different periods of time. It seems probable that some observers are much more interested in the swollen arm, or more aware of its implications, than olthers. For example, probably the largest singIe study of breast cancer before 1932 was Lewis and Rienhoffs22 analysis of 950 cases from the Johns Hopkins Hospital; though this study was otherwise most complete, the swollen arm was not mentioned Greenough and his asso- ciates11.12 and later Simmons et aL3* reported regularly their studies of cases from the Mas- sachusetts General Hospital without, as far as we know, discussing the swollen arm. Only rc- cently have Taylor and Wallace40 from this same group briefly referred to the subject, stat- ing that they find an incidence of 10 per cent

of “significant cases.” Before this time they had questioned the high incidence of lymphedema reported from the Breast Service of Memorial Hospital; and since they did not use roentgen- ray therapy as an adjunct in the treatment of operable breast cancer, they blamed, as was to be expected, the use of radiant energy for this complication. About other equally significant factors they chose to remain silent.

Daland’s* figures were difficult to interpret, since swelling of the upper and lower arm were separately reported, with no statement on how many patients had swelling of the entire arm. Fifty-five per cent had no swelling oP the Pore- arm, and 45 per cent none of the upper arm. Swelling of severe degree occurred in the upper arm in 5.5 per cent of patients and in the forearm in 6.6 per ccnt of patients. Nicolson and Grady29 noted absence of swelling in 56 per cent of their 230 paticnts treatcd by radical mastectomy, with slight swelling in 23 per cent and moderate or severe swclling in 21 per cent. Holman, McSwain, and Bea1,ls reporting on I00 radical mastectomies clone at the Kew York Hospital before 1943, found that 70 per cent ol the total scries had lymphcdema. Of seventy-one who had primary $kin graft, 35 per cent had no swelling, arid 65 per cent did have lymphedeina 01 some dep-ee.

Lobb and Harkins23 reported lyniphdeina in 80 per cent 01 sixty-five patients operated on. In 31 per cent the swelling was less than 1.5 cni., in 27 per cent, 1.3 to 2.9 cm., and in 22 per cent, 3 cm. or more. Villasor and 1,eu.i- son45 reported that among fifty patients with postinastectomy lymphedema, 33 per cent had swclling between 1 and 2 cm., 27.5 per cent, between 2.1 and 4 crn., and 39.2 per cent, 4 cm. or more.

REVIEW OF THE LITERATURE ON CAUSATION

Lymph a t i c S y s 1 em n n d L $1 m h e d c In a. Gray,lo studying in detail the superficial lymphatic system, found three layers. The first, or capillary layer, composed only OE endothelial cells, lay in the superficial dermis and was a continuous, intercommunicating system over the entire body. The second layer was at the junction of the dermis and the fat layer. This layer, consisting primarily of collecting radi- cals rather than capillaries, had a muscIe coat and valves. T h e vessels are two to ten times the size of the more superficial capillaries. Con- nected with these was a third layer, with muscle- coated vessels approximately twenty times the

446 CANCER May-June 1957 VOl. 10

size of the capillaries. This layer lay at the junction of the fat and the superficial fascia, but only infrequently in the deep fascia. The portions of the latter layer, which drained the hand and forearm, penetrated in general to the deep collecting trunks at the antecubital fossa; those draining the upper arm generally penetrated over a large area at the axilla. Gray also found variable pathways that anastomosed with the main vessels and appear to multiply when these were blocked.

Riouviere35 wrote that the deeper collecting trurlks accompany the large vascular or neuro- vascblar bundles and may be in contact with any of their components, artery, vein, or nerve alike. The same collecting trunk may, moreover, while enroute, change its position and successfully enter into immediate relationship with the veins, arteries, or nerves. The course of the deep lymphatics was often interrupted by intercollated nodules and the vessels them- selves united by transverse anastomoses.

Drinker and Yoffey? found that the muscu- lar coats of the lymphatics were slightly contrac- tile and played some part in the movement of lymph. However, they found that movement of lymph depended largely on normal activity of the body. Parsons and McMaster,32 and Cress- man and Blalock2 have obscrvcd that arterial pulsations aIso played an important role in causing movement of lymph.

Since Billroth in 1860 showed that within the seven days covered by his study, lymphatics did not grow across scar tissue, there have been many investigations of lymphatic regeneration. Eloessers noticed that edema often followed free grafts and also that when he attempted to induce local anesthesia by injecting procaine, it was almost impossible for the injection to diffuse beyond scar tissue. Rei- chert,34 working with Halsted, performed a partial amputation of a dog’s hind leg, sever- ing all lymphatic vessels but preserving major blood vessels and nerves. The wound was carefully reapproximated and united without infection and with minimal scar tissue. His observations on lymphatic regeneration across scar tissue were summarized: “The deep set of lymphatics was first demonstrated to show regeneration in a specimen made eight days after replantation. Both the superficiaI and deep sets were injected. The intrademal ink injections showed the superficiaI lymphatic system as tiny tortuous black lines just be- neath the skin extending to the line of union of the circular skin closure where, in various

areas, arborizations appeared and extended across the wound to €orm on the proximal side a converging fan of tiny vessels drawn into larger channels to the inguinal lymph glands. This bridging of the wound by new or regen- erating lymphatics occurred at sites where the primary wound healing had the least amount of reaction and scarring.”

Reichert found it impossible to determine the relative importance of the venous and lymphatic systems in the production of edema. The swelling began in these experiments on the fourth or fifth day and had subsided by the seventh or eighth day. Arterial vessels began to cross the operative field on the third day, but the venous and lymphatic vessels not until a day later. He considered that the operation had interrupted the normal balance of arterial and lymphovenous systems. He observed that venous regeneration was more ra- pid than lymphatic and that the main vein could be ligated at the height of the edema or at the beginning of its subsidence with no effect except a one or two days’ increased period of edema. If the vein were ligated after subsidence of the edema, there was no effect unless the lymphatics were blocked. After ten days, neither ligation of the main vein nor blockage of the lymph channels caused edema.

Drinker and Yoffey’ studied the effect of complete blockage of the lymph system. In the course of two and a half months, they suc- ceeded by repeated injections in blocking the lymph system in a dog’s leg. The first result was a pitting edema, followed by a “thin brawny edema,” indicating the beginning of fibrous changes. Eventually, typical elephantiasis developed, with extensive subcutaneous connective-tissue overgrowth. Autopsy demonstrated that lymph nodes and large trunks were sclerosed, and also that marked fibrosis was present. The Iymphatics were widely dilated, especially in the skin. Moreover, as soon as pitting edema was established, the fluid-protein lcvel rose; and as the lymphatic obstruction became defined, the area became suscept- ible to infection. Drinker and Yoffey concluded: “It can be pointed out with certainty that when the lymph drainage to a part is interrupted so that the various substances that under normal circumstances are removed by the lymphatics remain in situ, two things happen. First of all, there is extensive fibrous overgrowth and even involvement of the epithe- lium. Second, the part becomes strikingly sus- ceptible to infection, particularly to infection

No. 3 LYMPHEDEMA AFTER RADICAL MASTECTOMY - Treves 447

by streptococci. Furthermore . . . each attack of local infection simply intensifies what will occur inevitably. . . .”

Devenish and Jessope studied the venous and lymphatic status of ten postmastectomy patients. By elevation tests, and by direct measurements in three cases, they determined that venous pressure was not a factor in causing edema, nor did they find evidence of arterial disturbance. They concluded that increased venous pressure is very unlikely to cause edema without concurrent lymphatic blockage. Roent- genograms demonstrated in the swollen, but not in the normal, anns a coarse reticular pattern that was often sufficient to obscure the outline of the deep fascia. Since some patients exhibited this pattern within a twenty-four- day period after operation without evidence of inflammation, these investigators attributed this effect to distortion of the tissues by fluid rather than to fibrosis. Injection of highly diffusible dye into the edematous arm demonstrated that cutaneous lymphatics were dilated and abnormally permeable. About one half of the patients reported inlection at some time after they left the hospital, but in no instance did infection precede swelling, and swelling did not increase after inlection. Devenish and Jessop believed that the hard, brawny, non- pitting edema of the postmastectomy swollen arm may be due to increased fluid pressure rather than to fibrosis, but they also noted that this type of edema does not reduce as fully as does the pitting edema on elevation of the arm. Study of their small number of patients convinced these authors that the swollen arm could develop without either infection or irradiation as causes.

De Takats and Evoy; stated: “Blockade following extirpation of regional lymph nodes, X-ray therapy of regional lymph nodes or malignant invasions of these nodes will result in a central obstruction with secondary retro- grade changes in the peripheral lymphatics.” They found that when this occurred, injury, venous stasis, or increased capillary perme- ability might cause protein-rich interstitial fluid to appear and not be adequately carried away.

Kinnionth and Taylor19 studied the lymphatics of fifteen patients with idiopathic edema of the lower extremities and found ab- normal dilatation in a11 cases. Ey injecting dye before operation they were able to show that this dilatation had destroyed the function of the lymphatic valves. The amount of dilata-

tion was definitely related to the degree of lymphedema. Radioactive protein was absorbed about ten times as rapidly in edematous as in normal limbs and was even more slowly absorbed in one patient whose axillary nodes were obstructed by cancer. Inflammation OC.

curred in only six patients, and in them only alter the edema was established. These authors concluded that the inflammation was secondary.

Foley9 remarked that postmastectomy lymphedema was often complicated by cellulitis and erysipelas, which he stated were caused by reduced tissue immunity due to diminished lymph flow. He wrote: “The etiology of edema of an extremity following surgery is a controversial subject. . . . It is sufficient to say here that the surgical and radiation destruction of main lymph channels often do not leave patent vessels for adequate drainage. Fluid accumulates in the tissue spaces. In time, there is a connective tissue proliferation that converts the boggy areas into a fibrotic mass.”

Stewart and Treves39 reported on the occurrence of an entirely new and unrelated malignant tumor that developed in the lymphe- dematous arm long after the radical mastectomy had been performed. They reported six cases of lymphangiom-coma that was very ag- gressive and usually resulted in pulmonary metastases in spitc of shoulder-girdle amputa- tions. The gross and microscopic studies of the arms of these six patients showed that the destruction developed in this fashion: “It appears that following radical mastectomy, a moderate degree of fat necrosis occurs at the upper angle of the mastectomy scar. The entire fat layer is subsequently replaced by a fibrosis that continues down to and around the nerve, artery, and vein and is especially marked about the first portion of the axillary vein. Here a fine band of scar tissue not only com- presses the vesseI, but also acts as a sclerotic barrier to the deep lymphatics surrounding the vein.” This constricting band was observed in the axillary region, mesial and inferior to the insertion of the pectoralis-major muscle. This appeared to be the locus of the obscruc- tion in postmastectomy lymphedema.

Infation. As is well known, Halsted,l6 in his classic study of the swollen arm (1921), attributed this complication partly to interrup- tion of lymphatic flow but considered that the fibrotic development characteristic of the syn- drome was unlikely to appear except in the

448 CANCER May-June 1957 Vol. 10

presence of infection, which he believed might be light enough to be clinically unobserved. His first report of radical mastectomy, in 1891,l4 included an illustration showing not only the axillary dissection, but extensive wound suture within the axilla, well out on the arm, and also on the thorax immediately below the axilla. He allowed the wound in the axilla to fill with blood, buried sutures in the bIood clot, protected the whole with strips of gutta percha, and made the axilla as high as possible by a wedge of gauze maintained in position by firm bandages. By 1913,15 he had noted that this method of operation lcd to axillary scarification, delay in wound healing, and slight infection; also that i t resulted in enough tightness so that the patient might have difficulty dressing her hair. He then modi- fied the procedure that is now known as the Halsted operation for breast cancer, with routine skin gralting, and reported his first patients operated upon according to this method in 1913. niter the change, he was able to report greatly reduced marginal necrosis, im- proved arm function, and rarely a swollen arm.

In this connection, i t should be noted that the strongest argument for immediate grafting lies in its reduction of the dead space between the skin and the axillary structures, which is the site in which infection usually develops. This axillary dead space is minimal when the upper skin fold is sewed to the chest wall so that it surrounds the remaining axillary structures intimately and a graft is used to remedy the defect. Likewise, the dead space may be greatest when the lateral skin flap is drawn under tension over the axilla. T h e result is likely to be a tenting, which produces an empty space in the form of a truncated rhom- boid with the apex close to the axillary artery and vein. Lymph, blood serum, blood, and liquefied fat collect in this space and form an ideal medium for bacterial growth, followed by granulation tissue and not infrequently by a constricting cicatrix. In addition, if skin margins slough, bacteria carried by the lymphatics may invade as iar as the axilla.

NonetheIess, lrom recent reports, grafting does not appear to prevent the swollen arm. Holman, McSwain, and Beall8 reported that 65 per cent of their seventy-one patients with grafts and 83 per cent of twenty-nine patients not having grafts had swollen arms. This difference is probably not statistically significant, since the group contained only twenty-nine nongraft cases. No statement is made asso-

ciating infection with grafting or nongrafting procedures. Howevrr, it was noted that iorty- one patients later developed iniection of some type, and that striking swelling had occurred only in those who did have such late infections. The authors concluded that postoperative infection was a significant factor in the occurrence of lymphedema following radical mastectomy.

Neumann and Conway28 reported their analysis of 308 mastectomy cases, in ninety-five of which grafting was omitted. For 287 of the total series, data concerning the swollen arm was given; 129 had no swelling (45 per cent), 124 had moderate swelling (44 per rent), and thirty-four (11 per cent) had marked edema. Because swelling was not reported in relation to gralting, no conclusions can be drawn from this report. Sincc the largcr proportion of the series had pat t ing and the incidence of swelling was 56 per cent, there is some wggestion that grafting probably does not lead to as low an incidence of swelling as is reported in some qeries.

Villasor and Lewison45 found no correlatioil between grafting and the swollen arm, but they did find that infection plaved either a direct or an aggravating role in 15.7 per cent of tlicir cases ol swollen arm. Kinmonth and Taylor’slg fifteen patients with swollen arm included six with secondary inflammation, but none in whom infection could have been considered a primary cause of the swelling.

Venous Obstruction. Veal44 nearly twenty years ago reported an incidence of lymphedema in onlv 10 per cent of swollen arms and attributed the remainder to venous obstruction. He considered that lymphedema might appear later in the presence of superimposed infection. This conclusion resulted from his clinical observation that only 10 per cent of his patients exhibited brawny edema, which he considered due to lymphatic obstruction. Other authors believed this to be characteristic of advanced and severe cases. Since the length of his follow-up periods was not reported, the duration of the swelling is not indicated. He failed to mention the color changes or the supcrficial venous svmptoms characteristic of venous obstruction. He interpreted venograms as indicating a sufficient interference with venous return to account for the swelling. The roentgenograms reproduced were taken with the arms close to the side, a position that may cause temporary angulation of the axillary vein. I n many cases, a large number of col-

No. 3 L Y M P ~ D E M A AFTER RADICAL MASTECTOMY - Treves 449

lateral veins were evident. Thus the inade- quacy of venous flow does not seem too clearly demonstrated. Gumrich13 indicated by venograms for his patients that compression of the axillary veins was largely responsible for the swollen arm. Neither Veal nor Gumrich com- mented on the integrity of the lymphatic SYS-

tem. Russo, Parker, and Ma thews36 made veno-

grams before and after operation and at twelve- to cighteen-month intervals thereafter. In five of the fifteen cases they found the axillary vein completely obstructed. In others they observed signs 01 mild or moderate distortion. Studies of postoperative venous pressure indicated that it was raised in correlation with venographic findings. They believed that the swelling was due to inflammatory changes in the vein and observed that i t usually subsided within three to Pour months. Parker, RUSSO, and OesterreicheF considered that thrombus at the site of the subscapular ligation may have caused vascular obstruction. Since no study of the presence of rhrombi in relation to the swollen arm has yet been made, this must remain for the present an open question. We believe that i t must occur more frequently than is surmised. Its early occurrence may be manifested by a purplish suffusion in a swollen forearm. It may appear early in the postoperative period and must be distinguished from angulation of the axillary vein.

Phlebogaphic studies by Schorr and his as- sociate~~? were designed to demonstrate the presence or absence of axillary-vein obstruction and the patency of the cephalic vein. The investigation included fifteen patients with and eighteen without swollen arms. T h e authors observed no correlation between venous 3bstruction and edema but noted that the Eephalic vein was clearly visualized in sixteen If the patients without swelling. T h e integrity >f the blood flow in the cephalic vein was :onsidered important in preventing postmastectomy swollen arm. With this opinion we are n complete agreement. They believed that the renogram is very difficult to interpret because If anatomical variations in the venous pattern, md even more difficult when pathological :onditions cause dynamic changes in blood low. They also believed that the emphasis of ome authors on the role of venous defect as a .awe of the swollen arm is due to misinter- >retation of the complex factors involved in he phlebogram.

On the other hand, there is much evidence

that venous obstruction need not cause postoperative swelling of the arm unless obstruction is present in or about the transverse cervical axis. Halsted in 192116 reported that excision of the axillary or supraclavicular veins rarely was followed by swollen arm. He believed that obstruction of venous or lymphatic channels might contribute to edema but believed these phenomena were unimportant in the absence of infection.

Probably the first report devoted exclusively to the cffect of axillary-vein resection on the swollen arm was that of Costantinil in 1932. H e resected the axillary vein of nine patients and observed immediate swelling that subsided as collaterals developed. His pcriod of observation, as he acknowledged, was only two years, too short a timc to eliminate fully the possibility that lymphedema might develop. He believccl, however, that less than the usual number of cases would develop later because hc had removed the nerve supply of the win, and he agreed with Leriche and KunlinZi that these nerves played a primary role in causing lymphedema.

N e u h o P resected the axillary vein in eleven radical-mastectomy cayes and believed that in doing so he removed more completely the metastatic lymph nodes from the axilla. Among the patients treated in this manner, two had some edema and two others exhibited a fluctuating swelling of the hand. In the discussion of Neuhof's paper, Simkin agreed that resection of the vein did not cause much edema, but he observed that i t did delay the return of arm function. He did not consider that the anatomical relationship between the lymph vessels and the veins is ordinarily so in- timate as to require more than a stripping of the adventitia. However, it may be stated that operative manipulation or trauma or occa- sional ligation of the axillary artery may result in reflex venospasm. Until this observation can be proved, neither routine stellate- ganglion block nor arterial sympathectomy may be included as part of the routine in radical mastectomy.

Between 1944 and 1948, Macdonald24 resected the axillary vein in fifteen patients, carefully preserving the cephalic vein. This procedure he feIt jurtified in view of our experience with axillary-vein resection. The method, he concluded, permitted decidedly more thorough removal of the axillary and retrovenous lymph nodes. Consequently, he considered that axillary-vein resection might


eliminate foci of metastasis not reached in any other way. The low incidence of significant lymphedema in this series led Macdonald and Osman25 to continue the practice of resecting the axillary vein, and by 1955 they were able to report a total of fifty-five patients treated in this manner. Statistical analysis indicated that venous resection did not increase the incidence of swelling. In addition, Macdonald studied six cases with swelling and four with- Out, taking multiple venograms timed to pho- tograph at 0.1-second intervals. Only one patient with edema of more than I cm. showed any evidence of axillary compression, according to the venograms, and in this case the multiple venograms disclosed that the vein dou- bled in size when the arm was extended. Mac- donald pointed out that this experience illu- strated how easy it is to misinterpret single venograms. Axillary compression was clearly present in two patients without swelling.

Vasos~asm. Leriche and Kunlin,21 investigating thrombophlebitis, found that the clinical manifestations were due to a vasomotor reflex set u p in the thrombosed portion of the vein. T h e process, according to these authors, depended on the amount of vein involved, on arteriolar spasm, and-more important-on venospasm.

Ochner and DeBakey,30 also investigating thrombophlebitis, summarized their experi- mental evidence and clinical experience as follows: “Based on our clinical and experi- mental observationy, we believe that vasospasm, resulting from impulses originating in the involved venous segment, is one of the most important factors in the production of the clinical manifestations. These vasospastic influences probably affect both arterioles and veins. That a localized thrombophlebitic process can initiate a marked vasospasm is illu- strated by numerous reports. . . . As the result of vasospasm there result increased filtration pressure, relative anoxia of the capillary epi- thelium, and diminution in the flow of lymph, all of which increase the amount of perivascu- lar fluid.”

Impressed bv these and simiIar studies, Hanelin and his associates17 have studied the effects of injecting procaine into the stellate ganglia of twenty-five patients with postmastectomy lymphedema. In these cases, the swollen arms averaged 1 in. larger than the arms on the nonoperated side and were from 0.5 to 1.0 degree colder. Immediately after the injection, twenty patients, or 96 per cent,

noted a feeling of warmth in the arm. Tem- perature recordings indicated an average rise of 4 degrees. Increased flexibility, relief of pain, and a decrease in paresthesia and hyp- esthesia were noted in all instances. More than 80 per cent of the patients treated re- vealed persistent subjective and objective improvement after the paravertebral block. The greatest improvement was noted in those who had received two or more injections. The size of the arm did not diminish in 47 per cent, while in the other 53 per rent the reduction averaged three quarters of an inch.

Ladman, Martin, and Tue11,zO using Knise- ley’s transillumination apparatus in a study of dog mesenteric vessels, verified the importance of spasm as a factor affecting both veins and arteries. They found that the occlusion of veins caused spasm in both the veins and the arteries and that occlusion of arteries had similar effects on both types of blood vessels. Such spasm could be of an intensity sufficient to produce thrombi in a previously healthy vessel.

Obesity. It cannot be denied that the obese patient is uwally more prone after radical mastectomy to have increased postoperative drainage; in these patients liquefaction of fat is more common, skin edges necrose more frequently, and serum collection seems a greater problem. These factors may be in direct proportion to the weight of the patient. As Mac- donald rema~ked,~5 obesity is commonly recog- nized as a factor predisposing to the swollen arm. I t was also generally considered that higher degrees of adiposity are particularly likely to be associated with development of lymphedema after radical mastectomy. In his series, Macdonald found that seven thin persons had slight to moderate swelling, whereas thirty average or obese persons had moderate or severe swelling. Indeed, Macdonald observed that obesity was the most important single factor predisposing to the swollen arm in his group. He suggested the following sequence as influenciny the development of swelliny in the obese: fat necrosis, secondary infection, regional lymphangitis, and obstruction. He also considered that wide separation of superficia1 from deep lymphatics by the large quantity of fat may he a hindrance to drainage of the superficial lymphatics. These findings are in complete accord with penonal observations we had made prior to his report.

Devenish and Tessons explained the influence of fat on the swollen arm in terms of the inevitable removal of larger proportions of

No. 3 LYMPHEDEMA AFTER RADICAL MASTECTOMY - Treves 45 1

lymphatics in the process of excising the ex- ceptionally thick pads of fat during the development of the lateral flaps in obese patients undergoing radical mastectomy.

I t seems, therefore, surprising that Villasor and Lewis01145 found no relationship between obesity and the swollen arm in their analysis of fifty cases. Closer study did, however, dis- close that when the moderately obese developed swelling i t tended to be more than usually severe. In their series, lymphedema was associated especially with irradiation, poorly placed incisions, excision of the clavicular head of the pectoralis major, and tight scars. We are in agreement, except for the statement that complete removal of the pectoralis major muscle may be responsible for the swollen arm. This statement seems difficult to rationalize.

Irradiation. Macdonald found that irradiation added to the incidence of swelling after mastectomy whether or not axillary veins were resected. He wrote: “Since the only known method by which radiation causes swelling at any site is by lymphatic blockade, this is a ra- tional assumption.” 25 However, postradiation fibrosis would seem to offer a more logical explanation.

Villasor and Lewison45 observed that 57 per cent of fifty-one patients with lymphedema had received roentgen-ray therapy as compared with 39 per cent of twenty-eight patients without swollen arms. Onset oE swelling occurred immediately after the operation in 64.7 per cent of this series, between two and fourteen months after operation in 29 per cent. In this group, 5.9 per cent did not notice swelling until measurements disclosed its presence.

Foley,g discussing the controversial status of postmastectomy lymphedema, wrote: “It is sufficient to say here that the surgical and radiation destruction of main lymph channels often do not leave sufficient patent vessels for adequate drainage.” We feel that this explanation is faulty. The superficial lymphatics have been ablated, the profunda lymphatics have been resected with the axillary lymph nodes. The superficial anastomosis with the deep ones is of no avail if the return flow in the axilla has been blocked by a lack of continuity.

Neumann and Conway28 also found that a iignifican tly larger proportion of patients given roentgen-ray treatment had swdlcn arms than did those who were not so treated. Holman, McSwain, and Beall8 considered that roent- qenotherapy did not affect the incidence of the swollen arm unless it produced radio-

TABLE 1 CLASSIFICATION O F THE GROUP STUDIED

(1939- 1943) Grouv No. patients

~ ~~~

Primary operable 768 42 Primary operable after local excision

Primary operable, borderline 18 Primary inoperable, operated on 20

TOTAL OPERATED ON 848 159

TOTAL 1,007

Primary inoperable, not operated on -

dermatitis. However, 26 per cent of their sixty- six paticnts who received radiation were free from the swollen arm, in contrast to 37 per cent of the thirty-five who did not.

In light of these observations, there seems to be no plausible reason for using roentgen rays, as is recommended by West,46 in the treatment of swollen arm.

RESULTS

ANALYSIS OF CASES

Definition of Degrees of Swelling. We divided the swelling that occurred on the operative side after radical mastectomy into three groups: (1) temporary or slight, up to 3 cm. in circumference larger than the arm on the nonoperated side; (2) moderate, between 3 and 6 cm. larger, and (3) severe, 6 cm. or more. In most cases an estimated rather than an exact measurement was used. The severe group included many patients with swollen hands and forearms as well as swollen upper arms. While slight swelling may involve the entire arm, temporary swelling may be caused in the upper arm by constriction of the axilla through too tight a surgical dressing. Swelling did not cause significant dysfunction in any of these cases.

Description of the Series. During the five- year period between 1939 and 1943, there were 3,013 patients with cancer of the breast admit- ted to Memorial Hospital. For the purposes of

TABLE 2 OCCURRENCE OF SWOLLEN ARM,

PRIMARY OPERABLE CASES

Occurrence of swelling Number Percentage None 449 59 Slight or temporary 41 5 Moderate 28 4 Marked or prolonged 250 32

-

- TOTAL 768 100


TABLE 3 INTERVAL BETWEEN OPERATION AND

APPEARAkNCE OF SWOLLEN ARM (319 PATIENTS) _ _ -

Duration, mo.

Swelling Lqverage Med. Modal Range

Slight or temporary 18 3 6 6 6 0 < 1-82

Aloderate 2 3 0 9 0 2 0 1-72 Marked or

prolonged 11 1 6 6 3 5 < 1-82

this study, the charts of 1,007 were reviewed (Table 1). Our report is based primarily on the primary operable group, in which there were 848 patients having radical mastectomy. Included in this group were forty-two patients with disease classified as primary operable after local excision, eighteen borderline patients operated upon, and twenty with primary inoperable disease who had radical mastectomy. There weie 159 patients with inoperable disease who had no surgery.

In t idmce of Swelling. Of the 768 primary operable cases, 449, or 59 per cent, of the patients had no swelliqg, arid 31 9, or 41 per tent, did have swelling (Table 2). This is a considerable reduction in incidence since our estimates of 1931, when the figure was between 70 and 75 per cent. The change may be attributed to iinproved surgical techniques, a more complete undentanding 01 the mechanisms causing lymphedema, and the use of antibiotics lor the prevention and control O F infection. Among patients whosc disease wa5 considered operable after local excision, the incidence or the swollen arm waq 36 per cent; among borderline

cases, 45 per cent: among those considered inoperable but having radical mastectomy, 30 per cent, and among those considered inoperable and not having radical mastectomy, 15 per cent. Except for the latter, the groups were so small that considerable variation might be expected.

Interval Between Operation and Appear- ance of Swollen Arm. Table 3 indicates the extreme variation in time after radical mastectomy at which the swollen arm may appear. Marked or prolonged lymphedema appeared on an average of 11.1 months after the operation, slight swelling after 18.3 months, and moderate swelling, 23 months. T h e median time before this complication appeared was almost identical for slight and severe swelling, approximately six and one half months; the median was nine months for those with moderate swelling. The modal time was six months for slight swelling, two for moderate, and three and a half for marked swelling. I t is possible to conclude only that the time of appearance of the swollen arm after radical mastectomy in this sample was extremely variable, and that the severity of the swelling could not be statistically correlated with the time at which it appeared.

CAUSATIVE FACTORS

Table 4 compares degree of swollen arm with axillary metastases, irradiation, infection, and wound healing for the total group with primary operable disease (768 patients).

Irmdintion. A9 Table 1 zhows, the most

TABLE 4

TO Sn'ELLIh-i(; RE1,~TIONSIIIP OF XXII,I,,\RY R.TCTASTASES, IRR.4DI \TIOX, INFECTIOK, 2ND HEALING

~- ~~ ~ ~~ ~~ ~~ ~- ~ -

Dcgrce ot swelling ~- ~~~~~

None S1. or temp. Mod hllrd. or prol. ~ ~~~

NO. pt. NO. % KO. % No. '% No. % - ~ _ _ _ _ ~ Akxillarv metastases 436 224 51 20 5 18 4 174 40 No axillary metastases 326 222 68 21 7 10 3 73 22 Axillary metastases not qtated 6 3 5 0 0 0 0 0 3 50 Radiation 478 238 50 16 3 23 5 201 42 No radiation 287 211 75 25 8 5 1 46 16 Radiation not stated 3 0 0 0 0 0 0 3 100 Infection 140 66 47 13 9 10 7 51 37 No infection 625 383 62 28 4 18 3 196 31 Infection not stated 3 0 0 0 0 0 0 3 100 Healing per primam 368 238 65 12 3 8 2 110 30 Healing by secondary intention 397 211 53 29 8 20 5 137 34

0 0 0 0 0 3 100 Healing not stated 3 0

768 449 59 41 5 28 4 250 32 - - - - -

~~ _ _ ~ ~ ~

TOT~L -

No. 3 LYMPHEDEMA AFTER RADICAL MASTECTOMY Treves 453

striking factor associated with the postmastectomy swollen arm was irradiation. Of the patients who were given radiation, only 50 per cent had no swelling, and 42 per cent developed marked swelling. For thosc who were not given radiation, 75 per cent had no swelling, and only 16 per cent had marked swelling. Thus, 25 per cent more patients who did not receive radiation were free from swollen arms.

It is interesting to compare our figures with those of Holman, McSwain, and BeaI.lY They had sixty-six patients who received roentgenotherapy; seventeen (26 pcr cent) had no swollen arms. Of the thirty-five who did not receive roentgen-ray therapy, thirteen (37 per rent) had no swollen arm. These figures are difficult to reconcile with ours. Six times as many of our patients received postoperative radiation therapy, yet among the groups not given radiation, we had twice as many with no swelIing (’75 pcr cent versus 37 per cent). The difference in the size of the two samples makes them incomparable. Possibly larger doses, methods of administration, or complications following irradiation may have been responsible for the divergent figures. In both series, irradiation was associated with a larger incidence of sw01- let1 arms.

In Table 5, the relative influence of preoperative and postoperative irradiation i s compared and the amount ol roentgenotherapy in each category indicated. Of the forty-four patients who received preopcrative radiation only, twenty-five (57 per cent) developed marked swclling and nineteen (43 per cent) had no swelling. Of the 431 patients who re- ccivcd postoperative radiation only, 174 (40 per cent) developed marked swelling, and T’ery small percentages had slight or moderatc swelling. In 287 patients who did not receive men tgen-ray therapy, the incidence of marked swelling dropped to 16 per cent (46 patients). T h e difference betwccn 57 per ccnt (marked swelling in preoperative radiation) and 40 per cent (marked swelling in postoperative radiation) is of borderline significance: In other words, preoperative radiation in this series was associated with a significantly higher incidence of marked swclling after radical mastectomy. However, for many years preoperative radiation has not been given t o patients with primary operable disease. Furthermore, average or large amounts of radiation are quite con- sistently associated with marked swelling in more than 90 per cent of the total numbcr of irradiated patients. Few-, if any, of the patients

TABLE 5

ON SWELLING INFLUENCE OF iZMOUNT OF RADLqTION

Swelling, no. cases

SI. or Mkd. or Radiation None temp. Mod. prol.

Preop. only Small Average Large Small-

average Large-

average Unknown

TOTAL (44)

Postop. only Small Average Large Small-

average Small-

large Small-aver-

age-large Averdge-

large Unknown

TOIAL

rrpop. i- postop.

Preop.-small Postop.-large Unknown

TOTAL (3)

(43 1

‘r0TAL R.\- DL4TION CASES (478)

IJnknoyn No radlatioii

(287)

3 6 6

0

1 3

19 I

(43 %) 20 48 23

29

31

45

15 6

218 __

(51%)

0 0 1

1 -

0 0 0

0

0 0

0 -

2

1

3

0

4

1 0

16

>

-_

(4%)

0 0 0

0 -

-

16

0 (3%)

2.5 . (8%)

0 0 0

0

0 0

0 -

2 8 1

3

1

4

4 0

23 I

(5%)

0 0 0

0 __ ~-

2 3 ( 5 P )

5 (1 %) ~~

2 9 8

2

3 1

25 -

(57%)

13 41 21

15

35

26

20 3

174 -

(40%)

1 >( I i” 1

2

20 1

3

46 (16%)

(42% I

~~ -

*One patient had a small amount of radiation pre- operativcly and a large amount postoperatively.

in this series had radiation dermatitis of a severity sufficient for it to be considered a factor in the development of the swollen arm.

Axillary Metavtnses. As Table 6 shows, 436 (57 per cent) of the total 768 patients had axillary metastases. 01 these, 31 per cent had no swelling and 40 per cent marked swelling. Of the 326 patients without axillary metastases, 68 per cent had no swelling and 22 per cent marked swelling. Comparison of these figures indicates that patients with axillary metastases were more prone to develop lymphedema of the arm.

Since both axillary metastases and roent-

454 CANCER Muy-June 1957 Vol. 10

gen-ray therapy apparently were associated with the incidence of the markedly swollen arm, a way of determining which was the significant variable was devised. T h e patients with and without axillary metastases were subdivided according to whether they received radiation therapy. Of patients with axillary mEtastases who did not receive radiation, 75 per cent had no swelling, and 15 per cent, marked swelling. I n contrast, of those with axillary metastases who received radiation, only 48 per cent had no swelling while 43 per cent had marked swelling.

T h e patients without axillary metastases who did not receive radiation had about the same incidence of swelling as did the nonirradiated with metastasis: 73 per cent had no swelling and 16 per cent had marked swelling. Of the patients who did receive radiation, 54 per cent were free from swelling and 39 per cent had marked swelling. Thus, we found a significantly higher occurrence of marked swelling in the irradiated group.

By submitting these figures to statistical analysis, we were able to eliminate axillary metastases as a factor, and again irradiation was found to be responsible for a larger incidence of swollen arms. Since a much larger proportion with axillary metastases received roentgen-ray therapy, such a conclusion was not un- expected.

Postoperatiue Infection. Of the total series of patients under study, 140 had infection (Table 7). A patient had infection if there was wound complication that produced a tempera- ture of 102.5’ F. or more that persisted for four or more days. Of the 625 patients who did not have infection, 62 per cent had no swollen arms, whereas 47 per cent of the 140 patients with infection failed to show this complication. Of those with infection, 37 per

TABLE 6 RELATION OF AXTLLARY METASTASES

AND RADIATION THERAPY TO SWELLING

Degree of swelling

S1. or Mkd. or None temp. Mod. prol.

A:rillary No. ~ - ~ ~

metast. pt. No. ‘34 No. Yo No. ’% No. yo M-etast. 436 224 51 20 5 18 4 174 40 XoX-ray 48 36 75 5 10 0 0 7 15 X-ray 388 188 48 15 4 18 5 167 43 No metast. 326 222 68 21 7 10 3 73 22 No X-ray 239 175 73 20 9 5 2 39 16 X-ray 87 47 54 1 1 5 6 34 39 &rf-tnst. rot

stated 6 3 5 0 0 0 0 0 3 50

TABLE 7 RELATION OF INFECTION AND RADIATION

THERAPY TO SWELLING Degree of swelling

S1. or Mkd. or None temp. Mod. prol.

No _ _ _ _ _ _ ~ ~ _ Infection pt. No. c”, No. To No, % No. %

~~

Infect. 140 66 47 13 9 10 7 51 37 NoX-rav 64 42 66 9 14 2 3 11 17 X-ray ’ 76 24 32 4 5 8 10 40 53 Noinfect. 625 383 62 28 4 18 3 196 31 NoX-rav 223 169 76 16 7 3 1 35 I6 X-ray 402 214 53 12 3 15 4 161 40 Infect. not

stated 3 0 0 0 0 0 0 3 1 0 0

cent developed marked swelling, compared with 31 per cent of those without infection. In addition, a somewhat larger percentage of patients with infection than of those without infection developed slight or moderate degrees of lymphedema.

Analyzing the patients with and without infection in relation to the administration of roentgen-ray therapy, we got a result similar to that found in the study of axillary metastases and irradiation. Again, the irradiated group had the higher incidence of marked swelling. If one eliminates the factor of irradiation, there was no significant difference between postoperative infection and no postoperative infection.

Excluding swelling from consideration and just studying preoperative irradiation as it is associated with infection, an interesting find- ing is observed. Out of forty-four patients who received preoperative radiation, 43 per cent (nineteen) developed infection postoperatively. Of the 718 patients who had no preoperative radiation, 121, or only 16 per cent, developed infection postoperatively. T h e difference was significant and suggested that there was a positive and significant association between preoperative radiation therapy and postoperative infection.

HPaling per Pvimam and Healing by Sec- ondary Intention. For the 368 patients who healed without delay, the incidence of marked swelling (30 per cent) was not significantly different from that for the 397 who had healing by secondary intention, 34 per cent swelling. When these groups were subdivided into those receiving and not receiving radiation, once again the factor of roentgenotherapy was associated with a higher incidence of swelling.

Obesity. I n this series, a patient was consid-

No. 3 LYMPHEDEMA AFTER RADICAL MASTECTOMY - Treves 455

TOT4L

20

~~~ -~

5 , 41 5%

FIG. I. Relation between obesity and o l swelling. ' YE" ' 150-159 160-169 170-179 180-189 190-199 ' ZOO+

Weight in Pounds

ered obese who weighed more than 150 lb. Of 402 patients weighing less than this figure, 64 per cent had no swelling; whereas of 303 obese patients, 49 per cent had varying degrees of swelling (Table 8). Marked swelling occurred in 28 per cent of the nonobese and in 39 per cent of the obese. Statistical tests indicated that the difference was significant, and on this basis we must conclude that obesity had a positive relationship to the development of the swollen arm.

When obesity was considered in relation to irradiation, it was found that 48 per cent of

TABLE 8 RELATION O F OBESITY AND RADIATION

THERAPY TO SWELLING Degree of swelling

S1. or Mkd. or

NO> ~ - __ -_ Weight pt. No. % No. T, No. Cr, No. yo

Sorie k m p . hlod. prol.

~

< 150Ib. 402 258 64 20 5 11 3 113 28 No X-ray 148 120 81 10 7 3 2 15 10 X-ray 254 138 52 10 1 8 3 98 39 > 150 lb.

(obese) 303 154 51 16 5 15 5 118 39 YoX-ray 114 75 66 12 11 0 0 27 23 X-ray 189 79 42 4 2 15 8 91 48 Unknown 63 37 59 5 8 2 3 19 30

the obese patients and 39 per cent of the nonobese had marked swelling. Thus, there was a greater incidence of marked swelling among the obese. When the incidence of marked swelling in the nonirradiated patients who were obese (23 per cent) was compared with the incidence of marked swelling in nonirradiated, nonobese patients (10 per cent}, it was seen that a significantly greater perrentage of the obese had marked swelling. It was again evident that obesity influenced the development of the swollen arm.

Figure 1 illustrates the relationship between increasing degrees of obesity and the swollcn arm. Approximately 65 per cent of patients weighing up to 150 lb. had no swelling, and the percentage without swelling decreased so that only about 42 per cent of those weighing 190 to 200 lb. or more were free from swelling. On the other hand, marked swelling occurred in a little less than 30 per cent of patients weighing up to 150 Ib., increased rapidly so that nearly 45 per cent of those weighing 180 lb. had severe swelling: and at 200 lb., 55 per cent had marked swelling. Thus there was ample evidence that severe swelling increased with degrees of obesity and that the obese habitus must be considered a factor in the development of the swollen arm.

1156 CA~CLK M a y - J u n e 1957 Val. 10

TABLE 9 SiVELLING 4h20NG C-ISES PRIMARY OPERABLE AFTER LOCAL EXCISION, BORDERLINE,

AND INOPEIiABLE BUT OPEKA'I'ED OK* - _ _ ~

Primary operable after Primary operdble, Priman inoperable, local excision bordcrli ne operated on

No. N o No. No Yo. ?To pt. swelling Swelliiig pt. swelling Swelling pl. swelling Snelling

Axzllary metust. 18 9 (509,) 9 (SOTo) 14 8 (57%) 6 (43Tc) 1 5 10 (677,) 5 (337,) No X-ray 0 0 0 0 0 0 1 1 0 X-ray 18 9 9 14 8 6 14 9 5 No axzllary nzetust. 24 18 (75%) 6 (25%) 4 2 (50%) 2 (SOPo) 5 4 (80%) 1 (200/0) N o X-ray 17 14 3 1 1 0 0 0 0 X-ray 7 4 3 3 1 2 5 4 1 Infectzon 2 0 2 (100%) 7 3 (437,) 4 (57%) 0 0 0 NO X-ray 0 0 0 0 0 0 0 0 0 X-ray 2 0 2 7 3 4 0 0 0 -\To anfectzon 40 27 (67%,) 13 (33%) 11 7 (64%) 3- (36$) 20 14 (70%;,) 6 (30%) KO X-rav 17 14 3 1 1 0 1 1 0

___ _ _ _ _ ___

~~ ~~

X-ray 23 13 10 10 6 4 19 13 6 Heuling per primam 34 2 1 (62%) 13 (387,) 11 7 (64%) 4 (36%) 8 (637,) 3 (37%) N o X-rav 15 12 3 1 1 0 0 0 0 X-ray 19 9 10 10 6 4 8 5 3

No X-ray 2 2 0 0 0 0 1 1 0

Healing by secondary intention 8 6 (75%) 2 (25%) 7 3 (43%) 4 (37(r,j 12 9 (75%) 3 (25%)

2 7 3 X-ray 6 4 4 11 8 3 - __ - - - -_ - - -

42 27 (64%) 15 (36%) 18 10 (55%) 8 (45%) 20 14 (70%) 6 (30%) - _ _ _ - TOTAL

_ _ _ _ _ ~ *"Swelling" indicates marked or prolonged swelling.

Sunzmary. Of the factors studied, irradiation, especially preoperative irradiation, proved to be the most important on?. Axillary metastases could not according to our data be considered as influencing the development of swollen arm. There was definite evidence in our series that obesity was a factor in tlic production of the swollen arm.

CASES OPERABLE AF IER IBCAL EXCISION, BORDERLINE, AND INOPERABLE

Operable After Lorn1 ExciAion. A small group 01 €orty-two patients whose cancers were classified on admission to Memorial Hospital as primary operable after local excision else- where have been studied separately (Table 9). Among the patients in this category, 64 per cent did not develop swollen arms. Eighteen patients had axillary metastases, and twenty- four did not. All of the eighteen with axil1ar.y- node involvement were irradiated; nine de- velopcd marked swelling, while the other nine had no swelling. Of the twenty-four patients without axillary metastases, only six developed marked swelling, three of them after irradiation. Only tw70 patients had infected incisions; both developed severely swollen arms. Of those who did not have infection, a larger proportion of the irradiated than of the nonirradiated had swollen arms. The same

observation was niade for prompt healing. The group was probably too small for statistica1 significance, but again the administration of roentgenotherapy was associated with the swollen arm.

Bordrrline. The group oE borderline cases was quite small, eighteen cases (Table 9). Ten of the patients had no swelling, seven had healing per primam and no infection, although all but one received radiation. Eight of the patients without swelling were found to have axillary-node involvement and they were all irradiated. Of the two without axillary disease or swelling, onc had received radiation. Of the eight patients who had lymphedema, primary healing and infection occurred equally (four of each), while metastatic disease was present in six. All eight had received radiation preoperatively.

Primayy Inoperable with Opelntinn. Twenty patients with disease classified as primary inoperable had radical mastectomies, obviously too few for satisfactory analysis. Data are given in Table 9. Fourteen patients had no lymphedema, though nine had delayed healing. Ten were found to have involved nodes; four were free. All but one were irradiated. Of the six with marked lymphedema, ha11 had prompt healing and all had been irradiated. None had postoperative infections. A11 but one had axillary involvement.

No. 3 LYMPHEDEMA AFTER RADICAL MASTECTOMY * T?eves 457

Primary Inoperable, N o Opertxtinn. Only 15 per cent of the 159 with primary inoperable disease who did not have radical surgery developed marked swelling. T h e most striking ohsenation in this group was that an almost cqual percentage 01 those without and those with swclling were treated with large doses of roentgen rays (49 per cent and 52 per cent re- spectively). The inequality of the numbers in these two groups may partially invalidate this observation: twenty-three had marked or pro. longed swelling while 136 had no swelling. However, we think we may safely infer that the vast majority of inopeTable-breast-cancer patients do not develop the brawny arm. Per- haps some lethal metastasis intervened to cause death before the swollen arm developed in the patients not having operation.

MALE-BREAST CANCER

Thirty-two men were treated by radical mastectomy for breast cancer. Of thesc, only four patients (12.5 per cent) had swollen arms. Thirteen of fourteen with metastases and nine of ten without metastases had no swelling. Eleven of fonrteen and seventeen of eighteen not irradiated had no swelling. Neither of the two with infection had any swelling. It a p peared from this small group that men were less prone to develop lymphedema than women, this in spite of the fact that the disease otherwise paralleled behavior in the other sex.

DISCUSSION

The swollen arm is still the grcatcst long- range complication following radical mastectomy. If the operation is successfiil, the patient is anxious, for she has learned more about brawny edema from her fricnds than about any other one fact associated with the treatment of mammary cancer. If she does develop lymphedema, through the years she is handi- capped by the appearance of her arm. 4 t the time of operation it is impossible to foresee which patient may have a recurrence, or which of those successfully operated upon may at some later date have a swollen arm. If the complication is due to recurrence it rannot be avoided. But the danger of developing a swollen arm can be minimized by careful at- tention to preventive measures at the time of surgical intervention.

T h e incidence of lymphedema can be diminished by preventing postoperative infec-

tion, a complication produced by several factors, such as interference with drainage and development of necrotic skin edges. In every wound the period of postoperative drainage should be reduced to a minimum. Necrosis oE skin edges may in many instances be eliminated if the serum does not collect in the axilla, since the collection of fluid separates the flaps from the chest wall and thus interferes with the blood supply. Obliteration of the axillary dead space should also be avoided.

The use of preoperative radiation should be discontinued, and postoperative radiation should be judiciously employed in dosec that minimize the complication attendant upon its use. Possibly the obese patient should be convinced to diet in order to reduce her weight to the crucial 150 lb. Routine postoperative stellate-ganglion block might reduce the haz- ard of blood-vessel spasm.

It is well to remember that the omet of swclling in patients previouslv free from this complication may be initiated by any minor infection or trauma. Friction from clothing, trauma to the arm, a scratch or a mosquito bite, sunburn or a minor thermal injury, paronychia or ringworm of the nail, a cut at the time of manicure, any of these may induce lymphedema, which often persists. The cir- culatory balance is so fine that seemingly triv- ial incidents may produce this distressing complication; and, once produced, the process is rarcly reversible. T h e care of the arm and hand on the operated side should be an im- potrtant part of follow-up care. Patients should be instructed to avoid injury to the arm and chest wall and should have prompt care for minor traumas and infections.

SIJMMARY AND CONCL.IISTONS

It appears that lymphedema following radical mastectomy cannot be attributed to any solitary factor, but a combination 01 several factors may operate in any given case. Probably the most frequent cause is interference with the return of lymph because of ablation of the profunda lymphatics with the nodes of the axilla. Interference may be due directlv to the axillary dissection or to cicatrization following infection or fibrosis following roentgen-ray therapy. Angulation of the vein, interfering with both venous return and return of lymph from vessels in the wall of the vein, and reflex spasm of the axillary vein must likewise be assessed as bearing directly on the Droblem.

Certain other factors-roentgen-ray therapy, infection, presence or absence of axillary metastases, wound healing, and obesity-have been analyzed as they occurred in a total group of 1,007 patients a t Memorial Hospital between 1939 and 1943. Of this number, 848 were operated upon, the remainder being treated by roentgen rays because of inoper- ability. Of the 768 cases classified as having primary operable disease, the cases of 319 with swollen arms were analyzed. This study led to the following observations:

1. In this series, the swoIlen arm occurred in about 41 per cent of patients with primary operable breast cancer.

2. Roentgenotherapy, especially preoperative, appeared to be associated with the inci-

dence of the swollen arm in patients operated upon, but not in those who were not operated upon. Since this form of treatment is used mostly in cases of marked axillary involvement, the advanced stage oi disease may partially explain the association.

3. Obesity appeared to be a predisposing factor. This was particularly apparent in that increasing degrees of obesity were associated with larger percentages of patients with swollen arms. 4. T h e extent of axillary involvement alone

did not account for the Occurrence of lymphedema.

5. Postoperative infection and delayed healing alone were not associated with an increased incidence of the swollen arm.


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Documents

An evaluation of the etiological factors of lymphedema following radical mastectomy. An analysis of 1,007 cases