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Conservative treatment of postmastectomy lymphedema: A controlled, randomized trial
Annals of Oncology 2: 575-578, 1991. O 1991 Kluwer Academic Publishers. Primed in the Netherlands.
Original article Conservative treatment of postmastectomy lymphedema: A controlled, randomized trial G. Bertelli, M Venturini, G. Forno, F. Macchiavello & D. Dini National Institute for Cancer Research, Dept. of Rehabilitation, Genova, Italy
Summary. A controlled, randomized tried was carried out to evaluate the effectiveness of a new conservative treatment for postmastectomy lymphedema. Seventy-four patients were randomized to wear only an elastic sleeve for six months (group A) or to receive additionally an induction treatment with electrically stimulated lymphatic drainage (group B). The evaluation of results was focused not only on the mean variations in limb measurements in the two groups, but also on the frequency of clinically significant reductions of lymphedema (i.e., at least 25% compared to the initial values). A mean reduction of limb girth of about 17% was obtained in both groups, without significant differences between the two treatments. An 'objective response', however, was not achieved by the majority of patients. On the other hand, compliance to therapy was good and a significant result could be obtained simply and economically also in the group of patients treated only with the elastic sleeve. Key words: breast cancer, electrically stimulated drainage, elastic sleeve, postmastectomy lymphedema, randomized trials Introduction
undergo ESD sessions also wear an elastic sleeve during the day: hence, we decided to form a control group In spite of the fact that postmastectomy lymphedema of patients treated for the same period of time with the has been known for decades [1-3], affecting thousands elastic sleeve alone. Both groups of patients were folof women operated on for breast cancer who are often lowed for six months after the beginning of treatment otherwise free of neoplastic disease, the treatment of to assess maintenance of the response. this disorder has not yet been standardized. This is the result of a lack of both effective therapies and of wellconducted studies. Patients and methods Most patients are managed by conservative means, since no surgical procedure is entirely satisfactory Eligibility criteria [4-6]. There have been recent reports of the effectiveness of different conservative treatments, often based To be eligible, patients were required to have had a on sessions of pneumatic compression of the affected monolateral radical or modified mastectomy or quadlimb or of manual draining massage [7-10]. However, rantectomy with axillary node dissection; to have no even when some form of treatment is reported to have evidence of distant metastases or local relapse; to have produced a good average effect in a study group, it is a mild lymphedema of the homolateral upper limb (see difficult to judge the real benefits for the individual below for definition and measurement criteria), not to patient. Moreover, the concomitant use of elastic have been treated in the last six months, to have no sleeves or bandages, which per se may cause a reduc- signs of lymphangitis and to provide informed consent tion of lymphedema [11], may confuse the interpreta- to be entered in the trial. Patients were excluded if they tion of results. wore a cardiac stimulator or if radiotherapy or chemoThus, with the aim of evaluating the effectiveness of therapy were being administered. a new instrumental treatment of postmastectomy lymphedema and of assessing the possibility of apply- Definition and measurement of lymphedema ing the appropriate methodology of research and evaluation of results in this field, we have designed a con- Limb girth measurements of the affected and contratrolled, randomized trial. The new treatment is an elec- lateral side are recorded at seven matching points: trically stimulated lymphatic drainage (ESD) obtained hand, wrist, lower third of the forearm, upper third of through a sequence of impulses, which, in our experi- the forearm, elbow, lower third of the arm, upper third ence, has yielded encouraging results [12]. Patients who of the arm. The differences in circumference measure-
576 ment between the affected and the contralateral side at each point are added together; the result is termed delta. Only patients with a delta value above 10 centimeters are considered to have a clinically significant lymphedema and admitted into the trial. To restrict variability in the study population, patients with delta > 20 centimeters were excluded. Treatment All patients were instructed to wear a standard (not custom-made) hand-to-shoulder or wrist-to-shoulder elastic sleeve for six hours every day (SigVaris 503). Patients randomized to arm B (see below) also received an induction treatment with ESD (ICH8 Linfomed, Fisioline), applied in two cycles of two weeks each, divided by a 5-week interval. Each cycle consists of 10 30-minute sessions. The frequency of impulses is 4.5 KHz, the intensity being the maximum tolerable by the patient without discomfort. Eight electrodes are employed: the catode is placed on the elbow; the others are distributed from the supraclavicular region to the wrist over lymphatic stations or motor points. The first impulse of each cycle of stimulations drains the supraclavicular lymphatic area; the second sequence of impulses stimulates first the deltoid muscle and then the supraclavicular area again; the third sequence stimulates the triceps, the deltoid and the supraclavicular area and so on until the seventh electrode. This sequence is supposed to produce a deep lymphatic drainage, inducing a lymph flow from the lymphedematous areas of the limb to the lymphatic collectors of the supraclavicular and shoulder region, which are drained and emptied by the first impulses of the cycle. No other concomitant treatment for lymphedema was permitted during the trial. Instructions were given regarding skin care and prophylaxis of infections. Accrual and randomization Seventy-four patients were entered into the trial and randomized to treatment A (elastic sleeve only: 37 patients) or treatment B (elastic sleeve plus two induction cycles of ESD: 37 patients).
responders to treatment, patients who show variations (either a reduction or an increase) <25% are considered stable and patients whose delta increases more than 25% are considered as progressed and withdrawn from the study. The significance of the differences between pre- and postreatment delta values and between the two treatment groups is evaluated by means of the Wilcoxon test and of the Mann-Whitney rank sum test. The differences in frequency of responses are tested with the chisquare or Fisher exact test when appropriate. Results The main patient characteristics are shown in Table 1. Of 74 randomized patients, 4 (two in arm A and two in arm B) refused to complete the first part of the trial. One patient in arm A was lost to follow-up; one patient in arm B interrupted ESD treatment due to the onset of a lymphangitis. Thus, 68 patients (34 in each treatment arm) are evaluable for response at two months after start. Between T2 and the end of the trial after six months from start, three additional patients were lost to follow-up in arm A and two in arm B; three patients in arm B were withdrawn due to a progression of their lymphedema, leaving 31 patients evaluable for arm A at T6 and 29 for arm B. Table 1. Patient characteristics. Arm A Median age, years (range) Previous surgery Halsted radical mastectomy modified radical mastectomy Quadrantectomy
Arm B
64 n
45-77
64 n
48-78
%
17 12 8
46.0 32.4 21.6
10 18 9
27.0 48.7 24.3
14 23
37.8 62.2
14 23
37.8 62.2
10 27
27.0 73.0
6 31
16.2 83.8
19 18
51.3 48.7
16 21
43.2 56.8
12 25
32.4 67.6
12 25
32.4 67.6
%
Previous radiotherapy yes no
Previous chemotherapy yes no
Previous treatment for lymphedema
Evaluation of response Measurement of delta was repeated at admission into the trial (TO), after two months (T2) and after six months (T6) following admission for patients in arm A. For patients in arm B, T2 corresponded to the end of the induction treatment with ESD. The results are evaluated according to the following criteria: a. absolute mean variation of delta values in the entire group of patients and in the two treatment arms at T2 and T6 compared with TO; b. frequency of variations of delta values above or below 25% of initial values. Patients obtaining a reduction of delta of at least 25% are considered
yes no
Previous lymphangitis yes no
Figure 1 shows the overall mean values of delta at the start of the trial, at T2 and T6. Mean delta value at start was 14.8 ± 0.3 cm: after two months it had significantly decreased to 12.3±0.5 (p<0.0001, Wilcoxon test); after six months it was still significantly lower compared to the initial values (12.0±0.6, p<0.0001). However, the reduction was similar in the two treatment arms (Fig. 2). Mean delta values in groups A and
577
Discussion
16 DELTA cm.
15 14
13
12
START
2 MOS.
6 MOS.
Fig. I. Reduction of lymphedema in the whole group of evaluable patients. 16 DELTA cm. 15
14
13
12
2 MOS.
START
6 MOS.
Fig. 2. Reduction of lymphedema in group A (full squares) and B (empty squares)
B were 14.6 and 15.0, respectively, at TO, 12.1 and 12.6 at T2, 11.6 and 12.4 at T6 (p = not significant in all cases). Table 2 shows the percentages of patients who had obtained a reduction >25% of their delta value at T2 and T6 (responders) and of patients who showed a stability of lymphedema or a progression. The response rate was not significantly different in the two arms. Table 2. Response rate. Arm A
Arm B
n
%
n
%
After two months Evaluable patients Objective response Stabilization Progression
34 10 24 -
91.9 29.4 70.6 -
34 13 18 3
91.9 38.3 52.9 6.8
After six months Evaluable patients Objective response Stabilization Progression
31 15 15 1
91.2 48.4 48.4 3.2
29 12 15 2
85.3 41.4 51.7 6.9
Objective response — reduction of delta >25% of initial value Stabilization - delta variation (reduction or increase) <25% Progression - delta increase > 25%.
The design of this trial incorporated two main requirements: a. a careful selection of an homogeneous group of patients with postmastectomy lymphedema and b. the effort to develop a rigorous methodology for the evaluation of the effectiveness of a new treatment modality, with an entirely new perspective or interpretation of the results. To our knowledge, this is the first instance in which a controlled, randomized design was used to assess the effectiveness of an instrumental treatment of postmastectomy lymphedema. Apart from the lack of control groups, all previous studies on this subject have tended to report only the mean results obtained in the group of treated patients as a whole but have failed to point out the real clinical significance of such results [4, 7-10]. This is why, in addition to evaluating the mean decrease of lymphedema measurements obtained, we have analyzed the percentages of patients who achieved what we consider a clinically meaningful result, i.e., a reduction of at least 25% of limb girth. A definition of responding, non-responding (stable) and progressing patients seems to allow an easier assessment of the value of a new therapeutic tool. In fact, analyzing only the mean variations of limb measurements in the study population as a whole and in the two treatment arms, we observed a significant reduction of lymphedema after two months, maintained until the sixth month, of about 17% of the initial values. However, only one-third of the patients achieved what we defined as an objective response at two months, while the majority remained substantially stable and a few patients progressed. It is noteworthy, on the other hand, that the continued use of an elastic sleeve not only maintained the decrease of lymphedema obtained after the induction treatment, but represented per se an effective palliative treatment. In fact, the patients in group A achieved a significant mean limb girth decrease as rapidly as did those in arm B, and subsequently maintained the response. Clearly, neither ESD nor the elastic sleeve are the definitive answer to the problem of postmastectomy lymphedema: on the basis of this study and on our previous experience with ESD as single therapy, they can both be considered as moderately effective treatments which will benefit a given subset of patients. In the present study the combination of the two did not result in an increase of effectiveness. Wearing an elastic sleeve is a simple and economical treatment of postmastectomy lymphedema: however, not all patients will be able or willing to use it with the same regularity as the women enrolled in this study. Such patients could benefit from ambulatory sessions of ESD or other treatments. With regard to these, our trial has shown that it is possible - and in our opinion necessary - to apply also in this field a rigorous methodology in research: future controlled studies should elucidate the role of other
578 widely employed conservative treatments of postmastectomy lymphedema, such as pneumatic compression or manual lymph drainage. In view of the fact that lymphedema - and its prevention and treatment - is likely to have an important impact on the quality of the life and physical self-image of the mastectomized patient, the study of this problem should not be considered a waste of time or resources in comparison to other types of clinical oncology research. Again, this subject is largely unexplored: future studies on postmastectomy lymphedema could include an evaluation of these parameters, in addition to the ones that we have investigated in our trial. References 1. Halsted WS. Swelling of arm after operations for cancer of the breast - Elephantiasis Chirurgica - Its cause and prevention. Bull J Hopkins Hosp 1921; 32: 309-13. 2. Foley WT. Treatment of edema of arm. Surg Gynec Obstet 1951;93:568-74. 3. Nelson PA. Recent advances in treatment of lymphedema of the extremities. Geriatrics 1966; 21: 162-73. 4. Lerner R, Requena R. Upper extremity lymphedema secondary to mammary cancer treatment. Am J Clin Oncol 1986; 9: 481-7. 5. Savage RC. The surgical management of lymphedema. Surg
Gynec Obst 1984; 159: 501-7. 6. Nava VM, Lawrence WT. Liposuction on a lymphedematous arm. Ann Plast Surg 1988; 21: 366-8. 7. Richmand DM, OTJonnel TF, Zelikowski A. Sequential pneumatic compression for lymphedema. Arch Surg 1985; 120:1116-9. 8. Swedborg L Effects of treatment with an elastic sleeve and intermittent pneumatic compression in postmastectomy patients with lymphedema of the arm. Scand J Rehab Med 1984; 16:35-41. 9. Zanolla R, Monzeglio C, Balzarini A, Martino G. Evaluation of the results of three different methods of postmastectomy lymphedema treatment J Surg Oncol 1984; 26: 210-3. 10. Raines JK, O'Donnel T, Kalisher L, Darling RC. Selection of patients with lymphedema for compression therapy. Am J Surg 1977; 133:430-7. 11. Zeissler RH, Rose GB, Nelson PA. Postmastectomy lymphedema: late results of treatment in 385 patients. Arch Phys Med Rehab 1972; 53: 159-66. 12. Dini D, Forno G, Chiara S, Abrignani M. Nuova metodica di trattamento del linfedema postmastectomia. JAMA (Italian Edition) 1988; 5:675-9. Received 18 March 1991; accepted 11 April 1991.
Correspondence to: DarioDini.M.D. Istituto Nazionale per la Ricerca sul Cancro V. le Benedetto XV, 10 16132 Genova, Italy
Original article Conservative treatment of postmastectomy lymphedema: A controlled, randomized trial G. Bertelli, M Venturini, G. Forno, F. Macchiavello & D. Dini National Institute for Cancer Research, Dept. of Rehabilitation, Genova, Italy
Summary. A controlled, randomized tried was carried out to evaluate the effectiveness of a new conservative treatment for postmastectomy lymphedema. Seventy-four patients were randomized to wear only an elastic sleeve for six months (group A) or to receive additionally an induction treatment with electrically stimulated lymphatic drainage (group B). The evaluation of results was focused not only on the mean variations in limb measurements in the two groups, but also on the frequency of clinically significant reductions of lymphedema (i.e., at least 25% compared to the initial values). A mean reduction of limb girth of about 17% was obtained in both groups, without significant differences between the two treatments. An 'objective response', however, was not achieved by the majority of patients. On the other hand, compliance to therapy was good and a significant result could be obtained simply and economically also in the group of patients treated only with the elastic sleeve. Key words: breast cancer, electrically stimulated drainage, elastic sleeve, postmastectomy lymphedema, randomized trials Introduction
undergo ESD sessions also wear an elastic sleeve during the day: hence, we decided to form a control group In spite of the fact that postmastectomy lymphedema of patients treated for the same period of time with the has been known for decades [1-3], affecting thousands elastic sleeve alone. Both groups of patients were folof women operated on for breast cancer who are often lowed for six months after the beginning of treatment otherwise free of neoplastic disease, the treatment of to assess maintenance of the response. this disorder has not yet been standardized. This is the result of a lack of both effective therapies and of wellconducted studies. Patients and methods Most patients are managed by conservative means, since no surgical procedure is entirely satisfactory Eligibility criteria [4-6]. There have been recent reports of the effectiveness of different conservative treatments, often based To be eligible, patients were required to have had a on sessions of pneumatic compression of the affected monolateral radical or modified mastectomy or quadlimb or of manual draining massage [7-10]. However, rantectomy with axillary node dissection; to have no even when some form of treatment is reported to have evidence of distant metastases or local relapse; to have produced a good average effect in a study group, it is a mild lymphedema of the homolateral upper limb (see difficult to judge the real benefits for the individual below for definition and measurement criteria), not to patient. Moreover, the concomitant use of elastic have been treated in the last six months, to have no sleeves or bandages, which per se may cause a reduc- signs of lymphangitis and to provide informed consent tion of lymphedema [11], may confuse the interpreta- to be entered in the trial. Patients were excluded if they tion of results. wore a cardiac stimulator or if radiotherapy or chemoThus, with the aim of evaluating the effectiveness of therapy were being administered. a new instrumental treatment of postmastectomy lymphedema and of assessing the possibility of apply- Definition and measurement of lymphedema ing the appropriate methodology of research and evaluation of results in this field, we have designed a con- Limb girth measurements of the affected and contratrolled, randomized trial. The new treatment is an elec- lateral side are recorded at seven matching points: trically stimulated lymphatic drainage (ESD) obtained hand, wrist, lower third of the forearm, upper third of through a sequence of impulses, which, in our experi- the forearm, elbow, lower third of the arm, upper third ence, has yielded encouraging results [12]. Patients who of the arm. The differences in circumference measure-
576 ment between the affected and the contralateral side at each point are added together; the result is termed delta. Only patients with a delta value above 10 centimeters are considered to have a clinically significant lymphedema and admitted into the trial. To restrict variability in the study population, patients with delta > 20 centimeters were excluded. Treatment All patients were instructed to wear a standard (not custom-made) hand-to-shoulder or wrist-to-shoulder elastic sleeve for six hours every day (SigVaris 503). Patients randomized to arm B (see below) also received an induction treatment with ESD (ICH8 Linfomed, Fisioline), applied in two cycles of two weeks each, divided by a 5-week interval. Each cycle consists of 10 30-minute sessions. The frequency of impulses is 4.5 KHz, the intensity being the maximum tolerable by the patient without discomfort. Eight electrodes are employed: the catode is placed on the elbow; the others are distributed from the supraclavicular region to the wrist over lymphatic stations or motor points. The first impulse of each cycle of stimulations drains the supraclavicular lymphatic area; the second sequence of impulses stimulates first the deltoid muscle and then the supraclavicular area again; the third sequence stimulates the triceps, the deltoid and the supraclavicular area and so on until the seventh electrode. This sequence is supposed to produce a deep lymphatic drainage, inducing a lymph flow from the lymphedematous areas of the limb to the lymphatic collectors of the supraclavicular and shoulder region, which are drained and emptied by the first impulses of the cycle. No other concomitant treatment for lymphedema was permitted during the trial. Instructions were given regarding skin care and prophylaxis of infections. Accrual and randomization Seventy-four patients were entered into the trial and randomized to treatment A (elastic sleeve only: 37 patients) or treatment B (elastic sleeve plus two induction cycles of ESD: 37 patients).
responders to treatment, patients who show variations (either a reduction or an increase) <25% are considered stable and patients whose delta increases more than 25% are considered as progressed and withdrawn from the study. The significance of the differences between pre- and postreatment delta values and between the two treatment groups is evaluated by means of the Wilcoxon test and of the Mann-Whitney rank sum test. The differences in frequency of responses are tested with the chisquare or Fisher exact test when appropriate. Results The main patient characteristics are shown in Table 1. Of 74 randomized patients, 4 (two in arm A and two in arm B) refused to complete the first part of the trial. One patient in arm A was lost to follow-up; one patient in arm B interrupted ESD treatment due to the onset of a lymphangitis. Thus, 68 patients (34 in each treatment arm) are evaluable for response at two months after start. Between T2 and the end of the trial after six months from start, three additional patients were lost to follow-up in arm A and two in arm B; three patients in arm B were withdrawn due to a progression of their lymphedema, leaving 31 patients evaluable for arm A at T6 and 29 for arm B. Table 1. Patient characteristics. Arm A Median age, years (range) Previous surgery Halsted radical mastectomy modified radical mastectomy Quadrantectomy
Arm B
64 n
45-77
64 n
48-78
%
17 12 8
46.0 32.4 21.6
10 18 9
27.0 48.7 24.3
14 23
37.8 62.2
14 23
37.8 62.2
10 27
27.0 73.0
6 31
16.2 83.8
19 18
51.3 48.7
16 21
43.2 56.8
12 25
32.4 67.6
12 25
32.4 67.6
%
Previous radiotherapy yes no
Previous chemotherapy yes no
Previous treatment for lymphedema
Evaluation of response Measurement of delta was repeated at admission into the trial (TO), after two months (T2) and after six months (T6) following admission for patients in arm A. For patients in arm B, T2 corresponded to the end of the induction treatment with ESD. The results are evaluated according to the following criteria: a. absolute mean variation of delta values in the entire group of patients and in the two treatment arms at T2 and T6 compared with TO; b. frequency of variations of delta values above or below 25% of initial values. Patients obtaining a reduction of delta of at least 25% are considered
yes no
Previous lymphangitis yes no
Figure 1 shows the overall mean values of delta at the start of the trial, at T2 and T6. Mean delta value at start was 14.8 ± 0.3 cm: after two months it had significantly decreased to 12.3±0.5 (p<0.0001, Wilcoxon test); after six months it was still significantly lower compared to the initial values (12.0±0.6, p<0.0001). However, the reduction was similar in the two treatment arms (Fig. 2). Mean delta values in groups A and
577
Discussion
16 DELTA cm.
15 14
13
12
START
2 MOS.
6 MOS.
Fig. I. Reduction of lymphedema in the whole group of evaluable patients. 16 DELTA cm. 15
14
13
12
2 MOS.
START
6 MOS.
Fig. 2. Reduction of lymphedema in group A (full squares) and B (empty squares)
B were 14.6 and 15.0, respectively, at TO, 12.1 and 12.6 at T2, 11.6 and 12.4 at T6 (p = not significant in all cases). Table 2 shows the percentages of patients who had obtained a reduction >25% of their delta value at T2 and T6 (responders) and of patients who showed a stability of lymphedema or a progression. The response rate was not significantly different in the two arms. Table 2. Response rate. Arm A
Arm B
n
%
n
%
After two months Evaluable patients Objective response Stabilization Progression
34 10 24 -
91.9 29.4 70.6 -
34 13 18 3
91.9 38.3 52.9 6.8
After six months Evaluable patients Objective response Stabilization Progression
31 15 15 1
91.2 48.4 48.4 3.2
29 12 15 2
85.3 41.4 51.7 6.9
Objective response — reduction of delta >25% of initial value Stabilization - delta variation (reduction or increase) <25% Progression - delta increase > 25%.
The design of this trial incorporated two main requirements: a. a careful selection of an homogeneous group of patients with postmastectomy lymphedema and b. the effort to develop a rigorous methodology for the evaluation of the effectiveness of a new treatment modality, with an entirely new perspective or interpretation of the results. To our knowledge, this is the first instance in which a controlled, randomized design was used to assess the effectiveness of an instrumental treatment of postmastectomy lymphedema. Apart from the lack of control groups, all previous studies on this subject have tended to report only the mean results obtained in the group of treated patients as a whole but have failed to point out the real clinical significance of such results [4, 7-10]. This is why, in addition to evaluating the mean decrease of lymphedema measurements obtained, we have analyzed the percentages of patients who achieved what we consider a clinically meaningful result, i.e., a reduction of at least 25% of limb girth. A definition of responding, non-responding (stable) and progressing patients seems to allow an easier assessment of the value of a new therapeutic tool. In fact, analyzing only the mean variations of limb measurements in the study population as a whole and in the two treatment arms, we observed a significant reduction of lymphedema after two months, maintained until the sixth month, of about 17% of the initial values. However, only one-third of the patients achieved what we defined as an objective response at two months, while the majority remained substantially stable and a few patients progressed. It is noteworthy, on the other hand, that the continued use of an elastic sleeve not only maintained the decrease of lymphedema obtained after the induction treatment, but represented per se an effective palliative treatment. In fact, the patients in group A achieved a significant mean limb girth decrease as rapidly as did those in arm B, and subsequently maintained the response. Clearly, neither ESD nor the elastic sleeve are the definitive answer to the problem of postmastectomy lymphedema: on the basis of this study and on our previous experience with ESD as single therapy, they can both be considered as moderately effective treatments which will benefit a given subset of patients. In the present study the combination of the two did not result in an increase of effectiveness. Wearing an elastic sleeve is a simple and economical treatment of postmastectomy lymphedema: however, not all patients will be able or willing to use it with the same regularity as the women enrolled in this study. Such patients could benefit from ambulatory sessions of ESD or other treatments. With regard to these, our trial has shown that it is possible - and in our opinion necessary - to apply also in this field a rigorous methodology in research: future controlled studies should elucidate the role of other
578 widely employed conservative treatments of postmastectomy lymphedema, such as pneumatic compression or manual lymph drainage. In view of the fact that lymphedema - and its prevention and treatment - is likely to have an important impact on the quality of the life and physical self-image of the mastectomized patient, the study of this problem should not be considered a waste of time or resources in comparison to other types of clinical oncology research. Again, this subject is largely unexplored: future studies on postmastectomy lymphedema could include an evaluation of these parameters, in addition to the ones that we have investigated in our trial. References 1. Halsted WS. Swelling of arm after operations for cancer of the breast - Elephantiasis Chirurgica - Its cause and prevention. Bull J Hopkins Hosp 1921; 32: 309-13. 2. Foley WT. Treatment of edema of arm. Surg Gynec Obstet 1951;93:568-74. 3. Nelson PA. Recent advances in treatment of lymphedema of the extremities. Geriatrics 1966; 21: 162-73. 4. Lerner R, Requena R. Upper extremity lymphedema secondary to mammary cancer treatment. Am J Clin Oncol 1986; 9: 481-7. 5. Savage RC. The surgical management of lymphedema. Surg
Gynec Obst 1984; 159: 501-7. 6. Nava VM, Lawrence WT. Liposuction on a lymphedematous arm. Ann Plast Surg 1988; 21: 366-8. 7. Richmand DM, OTJonnel TF, Zelikowski A. Sequential pneumatic compression for lymphedema. Arch Surg 1985; 120:1116-9. 8. Swedborg L Effects of treatment with an elastic sleeve and intermittent pneumatic compression in postmastectomy patients with lymphedema of the arm. Scand J Rehab Med 1984; 16:35-41. 9. Zanolla R, Monzeglio C, Balzarini A, Martino G. Evaluation of the results of three different methods of postmastectomy lymphedema treatment J Surg Oncol 1984; 26: 210-3. 10. Raines JK, O'Donnel T, Kalisher L, Darling RC. Selection of patients with lymphedema for compression therapy. Am J Surg 1977; 133:430-7. 11. Zeissler RH, Rose GB, Nelson PA. Postmastectomy lymphedema: late results of treatment in 385 patients. Arch Phys Med Rehab 1972; 53: 159-66. 12. Dini D, Forno G, Chiara S, Abrignani M. Nuova metodica di trattamento del linfedema postmastectomia. JAMA (Italian Edition) 1988; 5:675-9. Received 18 March 1991; accepted 11 April 1991.
Correspondence to: DarioDini.M.D. Istituto Nazionale per la Ricerca sul Cancro V. le Benedetto XV, 10 16132 Genova, Italy