Baumeister, Rüdiger

Hahn, D.

Seifert, J.

Wiebecke, B.

English

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Original Scientijic Report Experimental Basis and First Application of Clinical Lymph Vessel Transplantation of Secondary Lymphedema Rüdiger G.H. Baumeister, M.D. , Jürgen Seifert, M.n. , Baldur Wiebeckc. M.D., and Dietbert Hahn , M.D. Depanmenl of Surgery. Institu te for $urgical Research, Institute for Palhology. and Depanmcnl or Radiology. Universily of Munieh , Klinikum Grosshadern, MUßieh, West Gcrmany Lymphedemas duc to a blockage oe thc Iymph vesscls in the rool oe the extremilies were treated experimentally and c1iokully by autotransplantation oe Iymph ves.wls under the operating microscope. In experimentallymphedema of the hind leg of 10 dogs, an increased circumference or about 50 % was reduced 10 10% within 7 wecks by Iymph vessel transplantation. After removal or thc Iransplants. thc circumferences returned 10 pre·tnnsplantation \·alues. The pre-transplanbltion elevated inlralymphatie pressu~ of 12.5 torr (controls: 2.5 torr) was redueed 10 the normal range oe 3.5 torr after the transplantation . In 8 of 10 dogs, the pateney of the transplants could ~ demonstrated by inspection, Iymphography, and isotope injections. In all 10 dogs, pateney could be proved by histologie examination. The data indicate that Iymph vessel transplantation ean reslore the diminished Iymph-transporting capacity brougbt on by Iymphedema. In 2 patients, it was possible 10 prepare Iymph eollectors about 25 cm long. After the transplantation, the circumfer-enees diminished. Hy isotopes improved Iymphatic trans-port could be demonstrated after the operation. Autologous transplantation of Iympb vessels is a promising mcthod for the treatment oe secondory Iymphedema especially in the early stages. Secondary Iymphstatic edema of an extremity is usually caused by destruction of the Iymph vesscJs in the root of the cxtremities and by the inability of R eprint reqlles ts: R.G. Baumeister. M.D., Chirur-gische Klinik der Universität München, Klinikum Gros· shadem, Marchioninistrasse 15, 0 -8000 Munich 70, Fed-eral Republic of Germany. the Iymph vesscJs to regenerate. The diminished Iymph-transporting capacity is unable to handle the normallymphatic load and, therefore , edema devel-ops [I ]. Restoration of the Iymph-transporting ca-pacity is the only therapy to deal directly with the cause of lymphedcma. Microsurgical techniques allows an operation on single lymph vessels. The restoration of the Iymphatic pathways, Iymph co!-lectors that are especially adapted to the transport ofthe Iymph , appears to be the most promising way 10 achieve an adequate lymph tlow. Materials and Methods Experimental Iymphedema was produced in mon-grel dogs wilh an average weighl of28 kg. One hind li mb was operated on, the contralaterallimb serving as control. According (0 the mel hod of Clodius and Wirth [2], the hind Iimb was totall y transected exeep( thc femur, the femoral artery , vein and nerve , and the ischial nerve. The transection of the femoral vessels was performed with the aid of the operating microscope to clean the vessels of all Iymphatic tissue and to Iigatc and mark the Iranseet-ed lymph vessels. In order to prevent spontaneous regeneration of the lymph vesscls, a polyurethane-Teflon sheet (Epigard) was interposcd. Only the skin was sutured . This method leads to a total blockage of thc deep and superficial Iymphatic Fig. I. Patent lymph vesseltransplant 4 weeks aft er the autologous transplantation in dog (H-E. Objeeti ve 4 x). system. After onc weck. thc edema was full y devel-oped . Lymph collectors of the medial and superficial system of the contralateral thigh were removed from the Ie ngth of the thigh. The enlarged distal and the proximal Iymph vessels at the femoral vessels wcrc prepared , and 2-3 transplants werc inter-posed. End-to-cnd anastomoses were performed by a special tension-free anastomosi ng tcchnique 13]. Under thc operating microscopc. the angle suture opposite to the surgeon is done first. Thc back wall is sewn with interruptcd sutures , the wall being lifled only enough 10 allow the needlc 10 pass. The anastomosis is finishcd wi th sevcral interrupted sutu res of Ihe front wall. Throughout the anasto-mosing procedure , no transverse tension oceurs. The operat ions were performed at the aid of a Zciss operating microscope with a 40 x magnifieation. Absorbable, atraumalie, and monofi lament suture material was used IPolyglaetin 910 (Viery l)], the sizc ranging from 10-0 to 12-0. After a therapeutic phase of about 7 wecks, the transplants were prepared again Ihrough a small longitudinal inc ision . Pateney and funelion were tested and then the transplant s were removed. The palency of the transplants was proved by visual examination, by Iymphography using Lipiodol-UI-Ira Fluid. and by injecting isotopes (BI I-gamma globulin) al thc paw and mcasuring thc aet ivity al the groi n. The removed transplants were examincd histologieall y. The funel ion of the transplanted lymph eollectors was proved by measurcments of Ihe ci rcumfcrcnccs of the extremitics at the paw, mctatarsus . and lower leg. Furthermore, the funct ion was cxamined by measuring the intralymphatic pressure as an end pressure 14J. A Statham element was used for the measurement. The zero baseline was atthe level of the intralymphatie eann ula. Fig. 2. Two transplanted patent ly mph vesscls under the operating mieroscope 4 wecks after transplantation. Results In 10 dogs. experimental Iy mphedema was treated by autologous transplantat ion of Iymph eolleetors. In all 10 dogs. the palcncy eou ld be proved by histologie examination (Fig. I). In addition , in 8 of 10 animal s, thc patency ofat least one transplanted lymph vcsse! could be proved by intraoperati vc inspection wilh Iymphography and by isotopic in-vesligation during the reopcration after the thera-peutic phase . Two dogs could not be examined because of lech nical reasons . In Fig. 2, two trans-pianted Iymph vessels arc shown under the operat-ing mieroseope 4 weeks afte r autologous tnmsplan-tation. Figure 3 shows an example of the evaluation of the patcney by lymphography. One bigger and one smaller transplant ftlled with contras t med ium can be seen. Thc Iym ph is Iransported along Ihe Irans-piants to the proximallymph vessels. No collatcrals cou ld be seen. Injections of 1J11-gamma globulin were performed subcutaneously at thc paw. After al least 5 minutes , in order 10 allow the absorption of the globulin into the Iymph vessels and to cxc1 ude a false int ravenous injection during that time, a quick rise in aetivity could be seen al the groi n in both the eontrols and the Iransplanlcd legs and after stan-dardized movements . Afte r the induet ion of thc edema bcforc the transplant ation, no ri se in aetivity eou ld be dcteeted in the groin (Fig. 4). The measurement of the cireumfe rcnccs at dis-tinet levels of the operated hind leg compared wilh thc contralateral leg scrved as a criterion for the funetion of the transplan ts in restoring the transport capaeity of the totall y blocked Iymphatic outftow. Preopcratively, there was no difference in the cir-cumferenees between the two hind legs. After in-duetion of the edema. the eircumferenees of thc operated legs were significan tl y larger. After autol-Fig. 3. Lymphographic palent IranspianIs 4 wecks afte r aUlologous Iymph vessel mlnsplanlation (markcd by clamps). Injeetion of 1l1 1...,. globuline eontrol extrem'tv edem. inieGtion movemen ts (cpm ] after transplantation :[ '0;7 m~::; 10 ., ... ~o 5 10 15 [min] I , " , " [min] Hg. 4. Judgmcnt of Iymph flow of Ihe hind Icg of a dog was made by measuring aCl ivilY at the groin aft er subcu-taneous injection of IlI I·gamma globulin at the paw. ogous Iymph vessc1 transplantation , the circumfcr-enccs ofthe operated legs went back to the range of the control s at the paw and at the metatarsus. Only at the lower leg were the circumferences somewhat larger than Ihose of the conlrol eX lrem ities. After removal ofthe Iransplants, the circumfcrences we re again significantl y elevated . The comparison of the changes of the circumfer-ences in the operated legs thro ughout the experi-ment showed a significant cnlargement of the cir-cumferences after induction of the ede ma , signifi-cant diminution after lymph vessel transplantation, and again a s ignificanl enlargement after removal of the Iransplants. Thi s was ttue fot all 3 meaSutemen l levels: the paw, metatarsus, and lowet leg . The slight elevation of the cireumfetence al the metatar-Changes in the eircumrerenee at the paw of the dog [eml 20 rp < O.OOI~ ,. p < 0.001 ..... .--p < 0.01 "" " " , A lem] 15 10 , ~ operated extremity EID control-extremitv Changes in the circumference ~t the metatarsus of the dog rp < O,OOI ..... r-p < O,OOI ...... ,....p < O,OI ---. 1n "' 10\ ofedema In "' 10) 1n - 10) of transplant In · 6) B liI oper8ted extremity 1'.:§i!H cOOtrol·exl remity leml " " , c Changes in the circumlerence 3\ the lower leg 01 the dog ,, < 0',00', - 10\ rnm operated extremity I EB control ·extremity fig. 5. The therapeutic effect of Iymph vessel transplantation was evaluated by measuring several circumfercnces of the hind leg of the dog. A. Changes of thc circumfcrenccs at the paw. B. Changes of the circumference at the metatarsus. C. Changes of the circumfercnce at the lower leg. sus ofthe controlleg Is probably due to (he cannula-tion of the lymph vcsse ls for pressurc measurc~ me nts (Fig. 5). Figure 6 shows a n example of the therapeutie etfect of the transplantation of Iymph collectors on the expe rimental lymphedema of the dog. As a furt her paramcter for the function of the transplant s. thc inlralymphatic pressurc was mea-sured during the edematous state, after (he trans-plantation, and in eontro[s. Thc e nd pressure was found 10 be 2.5 to rr in the cont rol cxtremities . In the edematous leg. it was clevaled to 12.5 to rr. Afte r transplantation, the pressure subsided 10 the range of the eont rols at 3.5 to rr (Fig. 7). Clinical Use Fig. 6A. Lymphcdema of the left hind leg of a doS. B. Four wecks after autologous Iymph vcssc1 transplantat ion. The expe rime ntal dala indicated a the rapeuti c clfect of aulo logous Iymph vesscl transpla ntations fo r the treatment of a secondary Iymphedema. Therefore , this promising method was also used in humans. Our first patient was operated on in June 1980. After a traumatie injury at lhe right groin with severe infeclion. he developed a n edema of the right leg within one year. The max imal differe ncc in the circumference was 6 cm. No changes in the venous system at the groin we re seen by phlebograph y. Conservative therapy showed no success , so we decided 10 perform a Iymph vessel tra nsplanlation . [Torr] 20 " 10 5 Inualymphatic pressure .-p <0, 01 --. .-p < 0, 01 -. controls Iymphll'dema (n - 10) /n - 9) after transplantation /n - 8) Fig. 7. The function of lymph vesscJ transplants was evalualed by measuring the intra[ymphal ic end pressure. We were able to prepare Iymph eolleetors of the superficial medial system for the full lengt h of the left thigh. Two eolleetors with a length of 25 em were transposed to the right side via the symph ysis (Fig. 8). At the right grain , two end-to-e nd anasto-moses with a superficial und a dee p Iymph vesscl of the edematous leg were performed using the te n-sion-free anastomosing technique. Within onc week, the diffe renee in the eireumfe renec war rc-dueed 10 a maximum of I em. After a pefiod of over 9 months, this resull remains unehanged. Tcchne-tium-99m-albumin (Tecernin) was injected in the right foot to establish pateney. Afterwards, groin aetivity showed a rise in both grains with a dclay in the left grain . After massage of thc affeeted leg, an extra rise eould be deteeted in both groins (Table I). With the aid of the gamma earnera, the path of the transplants eould be fo llowed to the sy mphysis. There is an overlapping with the aeti vity in the bladde r (Fig. 9) . , j ,: Fig. 8. Lymph collectors of the lef! thigh lransposcd via Ihe symphysis. The seeond palient was a 57-year-old female. Two years ago, an anal eare inoma was treated by abdominoperineaJ cxtirpation of thc rectum with eonseeuli ve Iymph node extirpation at both groins, followed by radiat ion Iherapy. A progressive Iym-phedema developed over a 6-rnonth period . Scintis-eans with Technetium-99m-sulfur-colloid (Lym-phoszint) showed no Iymphat ie flow 10 the iliac nodes in the fight edematous leg. On the left side , there was no signifieant defeel in Iymph tmnsporta-tion. Surgicall y, two Iymph eolleetors were trans-posed via the sy mphysis and anastomosed end-to-end with the superfieia l and deep Iymphatic system. Within 3 wecks, the eircumferenees we re markedl y reduced especiall y at the lowe r leg (Table 2). This time, seinti seans showed a quick flow of the Iymph out of the ext remit y. Diseussion The restoration of a sufficie nt transporting eapacity ofthe Iymphatie system by transplant ation of lymph vessels was experimentall y aceompli shed in the most scvere form of Iymphedema. After the total bloekage of the Iymphatic system, a maJignant Iymphedema developed. Untreated, thi s leads to death from profuse loss of proteins Ihrough the skin . Our expcrienees with 5 dogs eorrespond to that of C10dius [5]. In elini cal situations, the defi-cieney of transporting capacity is less scvere than that of this experimental model. Anothcr important aspect is the devclopment of Table I. Half-life period corrected simultaneous rneasure rnent s of (he aclivilY in the right and left groin after suhcutaneous application of Tccernin in the first patient 's righl foot [t (counts/sec)l. Measurernent point (min) Right groin Left groin '0 200 20 100 260 100 150 1 240 140 IMassage of Ihe right lower leg was perforrncd after mcasurerncnt at 150 rnin. 200 280 300 230 270 330 250 260 280 Fig. 9. Lymphulic scinliscu n showing Ihe course of Ihe trunsplants to the symphysis. an infect ion and a scleros is of thc edcmatous limb with a thicke ning of the basal membrane of the Iymph capillaries a nd an accumulat ion of collagen fibers around the Iymph vcsscl [6]. For a full rehabilitation by Iymph vcssel transplantation, il is thercforc desirable 10 petform the operation in stage 1 of the Iymphcdema. As ct inical experience shows, there is also Iymph How alo ng fi brot ic Iymph ves-sels. Moreover. macrophages are able to desl roy the intcrstitial proteins [7, 81. Thereforc, a diminu-tion of the fibrosis might be possible after improve-ment of the Iymph ftow in stage 2. An alternate mcthod to the microsurgical Iymph vcssel t ransplantat ion is thc crcal ion of mi cro-Iymphove nous shunt s [9--11]. Since in edematous limbs spontaneous anasto moses have bcen seen [1 2J. lymphovenous anastomoses are onl y a quanti-tative improve ment of a compensation mechanism that is obv iously working insufficientl y. The vcnous peripheral pressure is higher tha n the intralymphat ic pressure, at least at rest [13]. Opera-tions dealing o nl y with thc Iymphatic system have the advantage that thc ri sk of a thrombosis is dimini shed by the low coagulation parameters of thc Iymph [14]. The transplantation of Iymph vcssel s eould also be added to a resectio nal procedure for trcating stage 3 Iymphedc ma. Recurrcnt cpi sodes 115] may be avoided by thc improvemcnt in thc transporting capacit y of the Iymphatic system. Acknowledgments We thank lutta Krumbach for her cxce llenltechni-cal assistance . The investigation was generously supported by a gra nt of the VW Foundatio n. References I . Földi, M. : Physiology and palhophysiology ofl ymph· flow. In Lymphedema. L. Clodius. cdi tor. Stullgart, Georg Thieme Publishers, 1977, pp. i- I i 2. Clodius, L. , Wirth , W.: A new experimental model for ehronic lymphedema ofthe extremities. Chir Plast (Ber!. ) 2: 11 5, 1974 3. Baumeister. R.G.H., Seife rt, J. , Wiebeeke. B. : T ransplantation of lymph vessels on rats as weil as a fi rs t therapcutic applieat io n on the c,,- perimental lym· phedcma of thc dog. Eur. Surg. Res. I1[Suppl. 2J:7, 1980 4. Olszewski , W.l. : Colleetion and physiological mea-sure men\S of peripherallymph and intcrs ti tial ßuid in man. Lymphology 10: 137, 1977 5. Clodius, L. : The experimental basis for the surgieal treatment of lymphedema. In Lymphedema. L. Clo-dius. editor, Stullgart . Georg Thie me Publishers, 1977. pp. 4~77 6. Olszewski W.: On the palhomechanism of dcvelop-ment of poslsurgicallymphede ma. Ly mphology 5:35. 1973 7. Casley-Smith, J .R.: A fine structural study of the removal of the eßectiveness of benzo-pyrone treat-ment ofl ymphedema by the destructio n ofthe mac ro· phages by silica. Br. J. Exp. Pat hol. 59(2): 116, 1978 8. Piller. N. B.: Lymphedema, macrophages and bcnzo-pyrones. Lymphology 13: 109. 1980 9. Nielubowicz. J ., Olszewski , W.: Surgieal lympho-venous shunts for decompression of secondary Iym-phoedema . J. Cardiovasc. Surg. (Spcc. Issue) 1966 Table 2. Prcoperative and postoperative circu mfe renees of the surgically treatcd right leg compared to those of thc untreated Icft leg in the sccond pat icnt . Thigh Knee Lower leg Ankle Metatarsus Left circumfcrences (cm) 57 41.5 38.0 22.0 23 .0 Right eircumferences (em) Preoperative 63.5 46.0 42.0 26.0 25.0 Postoperative 61.5 42 .5 39.0 23.0 23.0 lO. O'Brie n. H.M., Shafiroft', B.B.: Microlymphatico-venous and resectional surgery in obstructive Iym-phedema, World J . Surg. 3:3. 1979 11 . Degni , M.: New technique oflymphatic-venous anas-tomosis for the treatment of Iymphedema. 1. Cardio-vasc . Surg. (Torino) {9(5) :577, 1978 12. Edwards, J .M .. Kinmonth , J.B .: Lymphovenous shunt in man. Br. Med. J. 4:579, 1969 13. Yamada. Y.: Thc study of lymphatic venous anasto-mosis in Iymphcdcma. Nagoya J . Med . 31: 1. 1%9 14. Yoffey. J .M. , Courtice. F.C.: Lymphat ics. Lymph and the Lymphomyeloid Complex. London-New York , Academic Press. 1970 15, Clodius. L. : In vited commentary on " Microlympha-ticovenous and resectional surgery in obSl ruclivc Iymphedema," World J, Surg. 3: 121, 1979 

A fine structural study of the removal of the eßectiveness of benzo-pyrone treatment oflymphedema by the destruction ofthe macro· phages by silica.

A new experimental model for ehronic lymphedema ofthe extremities.

Lymphedema, macrophages and bcnzopyrones.

On the palhomechanism of dcvelopment ofposlsurgicallymphedema.

Physiology and palhophysiology oflymph· flow.

Surgieal lymphovenous shunts for decompression of secondary Iymphoedema.

The experimental basis for the surgieal treatment of lymphedema.

Transplantation of lymph vessels on rats as weil as a first therapcutic applieation on the c,,-perimental lym· phedcma of thc dog.

W.l.: Colleetion and physiological measuremen\S of peripherallymph and intcrstitial ßuid in man.

Experimental Basis and First Application of CLinical Lymphvessel-Transplantation of Secondary Lamphedema

Universität München: Elektronischen Publikationen

Original Scientijic Report 
Experimental Basis and First Application of Clinical Lymph Vessel 
Transplantation of Secondary Lymphedema 
Rüdiger G.H. Baumeister, M.D. , Jürgen Seifert, M.n. , Baldur Wiebeckc. M.D., and Dietbert Hahn , M.D. 
Depanmenl of Surgery. Institu te for $urgical Research, Institute for Palhology. and Depanmcnl or Radiology. Universily of Munieh , 
Klinikum Grosshadern, MUßieh, West Gcrmany 
Lymphedemas duc to a blockage oe thc Iymph vesscls in 
the rool oe the extremilies were treated experimentally and 
c1iokully by autotransplantation oe Iymph ves.wls under the 
operating microscope. In experimentallymphedema of the 
hind leg of 10 dogs, an increased circumference or about 
50 % was reduced 10 10% within 7 wecks by Iymph vessel 
transplantation. After removal or thc Iransplants. thc 
circumferences returned 10 pre·tnnsplantation \·alues. The 
pre-transplanbltion elevated inlralymphatie pressu~ of 
12.5 torr (controls: 2.5 torr) was redueed 10 the normal 
range oe 3.5 torr after the transplantation . In 8 of 10 dogs, 
the pateney of the transplants could ~ demonstrated by 
inspection, Iymphography, and isotope injections. In all 10 
dogs, pateney could be proved by histologie examination. 
The data indicate that Iymph vessel transplantation ean 
reslore the diminished Iymph-transporting capacity 
brougbt on by Iymphedema. 
In 2 patients, it was possible 10 prepare Iymph eollectors 
about 25 cm long. After the transplantation, the circumfer-
enees diminished. Hy isotopes improved Iymphatic trans-
port could be demonstrated after the operation. Autologous 
transplantation of Iympb vessels is a promising mcthod for 
the treatment oe secondory Iymphedema especially in the 
early stages. 
Secondary Iymphstatic edema of an extremity is 
usually caused by destruction of the Iymph vesscJs 
in the root of the cxtremities and by the inability of 
R eprint reqlles ts: R.G. Baumeister. M.D., Chirur-
gische Klinik der Universität München, Klinikum Gros· 
shadem, Marchioninistrasse 15, 0 -8000 Munich 70, Fed-
eral Republic of Germany. 
the Iymph vesscJs to regenerate. The diminished 
Iymph-transporting capacity is unable to handle the 
normallymphatic load and, therefore , edema devel-
ops [I ]. Restoration of the Iymph-transporting ca-
pacity is the only therapy to deal directly with the 
cause of lymphedcma. Microsurgical techniques 
allows an operation on single lymph vessels. The 
restoration of the Iymphatic pathways, Iymph co!-
lectors that are especially adapted to the transport 
ofthe Iymph , appears to be the most promising way 
10 achieve an adequate lymph tlow. 
Materials and Methods 
Experimental Iymphedema was produced in mon-
grel dogs wilh an average weighl of28 kg. One hind 
li mb was operated on, the contralaterallimb serving 
as control. According (0 the mel hod of Clodius and 
Wirth [2], the hind Iimb was totall y transected 
exeep( thc femur, the femoral artery , vein and 
nerve , and the ischial nerve. The transection of the 
femoral vessels was performed with the aid of the 
operating microscope to clean the vessels of all 
Iymphatic tissue and to Iigatc and mark the Iranseet-
ed lymph vessels. In order to prevent spontaneous 
regeneration of the lymph vesscls, a polyurethane-
Teflon sheet (Epigard) was interposcd. Only the 
skin was sutured . This method leads to a total 
blockage of thc deep and superficial Iymphatic 
Fig. I. Patent lymph vesseltransplant 4 weeks aft er the 
autologous transplantation in dog (H-E. Objeeti ve 4 x). 
system. After onc weck. thc edema was full y devel-
oped . 
Lymph collectors of the medial and superficial 
system of the contralateral thigh were removed 
from the Ie ngth of the thigh. The enlarged distal and 
the proximal Iymph vessels at the femoral vessels 
wcrc prepared , and 2-3 transplants werc inter-
posed. End-to-cnd anastomoses were performed by 
a special tension-free anastomosi ng tcchnique 13]. 
Under thc operating microscopc. the angle suture 
opposite to the surgeon is done first. Thc back wall 
is sewn with interruptcd sutures , the wall being 
lifled only enough 10 allow the needlc 10 pass. The 
anastomosis is finishcd wi th sevcral interrupted 
sutu res of Ihe front wall. Throughout the anasto-
mosing procedure , no transverse tension oceurs. 
The operat ions were performed at the aid of a Zciss 
operating microscope with a 40 x magnifieation. 
Absorbable, atraumalie, and monofi lament suture 
material was used IPolyglaetin 910 (Viery l)], the 
sizc ranging from 10-0 to 12-0. 
After a therapeutic phase of about 7 wecks, the 
transplants were prepared again Ihrough a small 
longitudinal inc ision . Pateney and funelion were 
tested and then the transplant s were removed. The 
palency of the transplants was proved by visual 
examination, by Iymphography using Lipiodol-UI-
Ira Fluid. and by injecting isotopes (BI I-gamma 
globulin) al thc paw and mcasuring thc aet ivity al 
the groi n. The removed transplants were examincd 
histologieall y. 
The funel ion of the transplanted lymph eollectors 
was proved by measurcments of Ihe ci rcumfcrcnccs 
of the extremitics at the paw, mctatarsus . and lower 
leg. Furthermore, the funct ion was cxamined by 
measuring the intralymphatic pressure as an end 
pressure 14J. A Statham element was used for the 
measurement. The zero baseline was atthe level of 
the intralymphatie eann ula. 
Fig. 2. Two transplanted patent ly mph vesscls under the 
operating mieroscope 4 wecks after transplantation. 
Results 
In 10 dogs. experimental Iy mphedema was treated 
by autologous transplantat ion of Iymph eolleetors. 
In all 10 dogs. the palcncy eou ld be proved by 
histologie examination (Fig. I). In addition , in 8 of 
10 animal s, thc patency ofat least one transplanted 
lymph vcsse! could be proved by intraoperati vc 
inspection wilh Iymphography and by isotopic in-
vesligation during the reopcration after the thera-
peutic phase . Two dogs could not be examined 
because of lech nical reasons . In Fig. 2, two trans-
pianted Iymph vessels arc shown under the operat-
ing mieroseope 4 weeks afte r autologous tnmsplan-
tation. 
Figure 3 shows an example of the evaluation of 
the patcney by lymphography. One bigger and one 
smaller transplant ftlled with contras t med ium can 
be seen. Thc Iym ph is Iransported along Ihe Irans-
piants to the proximallymph vessels. No collatcrals 
cou ld be seen. Injections of 1J11-gamma globulin 
were performed subcutaneously at thc paw. After al 
least 5 minutes , in order 10 allow the absorption of 
the globulin into the Iymph vessels and to cxc1 ude a 
false int ravenous injection during that time, a quick 
rise in aetivity could be seen al the groi n in both the 
eontrols and the Iransplanlcd legs and after stan-
dardized movements . Afte r the induet ion of thc 
edema bcforc the transplant ation, no ri se in aetivity 
eou ld be dcteeted in the groin (Fig. 4). 
The measurement of the cireumfe rcnccs at dis-
tinet levels of the operated hind leg compared wilh 
thc contralateral leg scrved as a criterion for the 
funetion of the transplan ts in restoring the transport 
capaeity of the totall y blocked Iymphatic outftow. 
Preopcratively, there was no difference in the cir-
cumferenees between the two hind legs. After in-
duetion of the edema. the eircumferenees of thc 
operated legs were significan tl y larger. After autol-
Fig. 3. Lymphographic palent IranspianIs 4 wecks afte r 
aUlologous Iymph vessel mlnsplanlation (markcd by 
clamps). 
Injeetion of 1l1 1...,. globuline 
eontrol extrem'tv edem. 
inieGtion movemen ts 
(cpm ] after transplantation 
:[ '0;7 m~::; 
10 ., ... ~
o 5 10 15 [min] 
I 
, 
" 
, 
" [min] 
Hg. 4. Judgmcnt of Iymph flow of Ihe hind Icg of a dog 
was made by measuring aCl ivilY at the groin aft er subcu-
taneous injection of IlI I·gamma globulin at the paw. 
ogous Iymph vessc1 transplantation , the circumfcr-
enccs ofthe operated legs went back to the range of 
the control s at the paw and at the metatarsus. Only 
at the lower leg were the circumferences somewhat 
larger than Ihose of the conlrol eX lrem ities. After 
removal ofthe Iransplants, the circumfcrences we re 
again significantl y elevated . 
The comparison of the changes of the circumfer-
ences in the operated legs thro ughout the experi-
ment showed a significant cnlargement of the cir-
cumferences after induction of the ede ma , signifi-
cant diminution after lymph vessel transplantation, 
and again a s ignificanl enlargement after removal of 
the Iransplants. Thi s was ttue fot all 3 meaSutemen l 
levels: the paw, metatarsus, and lowet leg . The 
slight elevation of the cireumfetence al the metatar-
Changes in the eircumrerenee at the paw of the dog 
[eml 
20 rp < O.OOI~ ,. p < 0.001 ..... .--p < 0.01 "" 
" 
" 
, 
A 
lem] 
15 
10 
, 
~ operated extremity EID control-extremitv 
Changes in the circumference ~t the metatarsus of the dog 
rp < O,OOI ..... r-p < O,OOI ...... ,....p < O,OI ---. 
1n "' 10\ ofedema 
In "' 10) 1n - 10) 
of transplant 
In · 6) 
B liI oper8ted extremity 1'.:§i!H cOOtrol·exl remity 
leml 
" 
" 
, 
c 
Changes in the circumlerence 3\ the lower leg 01 the dog 
,, < 0',00', 
- 10\ rnm operated extremity I EB control ·extremity 
fig. 5. The therapeutic effect of Iymph vessel 
transplantation was evaluated by measuring several 
circumfercnces of the hind leg of the dog. A. Changes of 
thc circumfcrenccs at the paw. B. Changes of the 
circumference at the metatarsus. C. Changes of the 
circumfercnce at the lower leg. 
sus ofthe controlleg Is probably due to (he cannula-
tion of the lymph vcsse ls for pressurc measurc~ 
me nts (Fig. 5). Figure 6 shows a n example of the 
therapeutie etfect of the transplantation of Iymph 
collectors on the expe rimental lymphedema of the 
dog. 
As a furt her paramcter for the function of the 
transplant s. thc inlralymphatic pressurc was mea-
sured during the edematous state, after (he trans-
plantation, and in eontro[s. Thc e nd pressure was 
found 10 be 2.5 to rr in the cont rol cxtremities . In the 
edematous leg. it was clevaled to 12.5 to rr. Afte r 
transplantation, the pressure subsided 10 the range 
of the eont rols at 3.5 to rr (Fig. 7). 
Clinical Use 
Fig. 6A. Lymphcdema of the left 
hind leg of a doS. B. Four wecks 
after autologous Iymph vcssc1 
transplantat ion. 
The expe rime ntal dala indicated a the rapeuti c clfect 
of aulo logous Iymph vesscl transpla ntations fo r the 
treatment of a secondary Iymphedema. Therefore , 
this promising method was also used in humans. 
Our first patient was operated on in June 1980. 
After a traumatie injury at lhe right groin with 
severe infeclion. he developed a n edema of the right 
leg within one year. The max imal differe ncc in the 
circumference was 6 cm. No changes in the venous 
system at the groin we re seen by phlebograph y. 
Conservative therapy showed no success , so we 
decided 10 perform a Iymph vessel tra nsplanlation . 
[Torr] 
20 
" 
10 
5 
Inualymphatic pressure 
.-p <0, 01 --. .-p < 0, 01 -. 
controls Iymphll'dema 
(n - 10) /n - 9) 
after 
transplantation 
/n - 8) 
Fig. 7. The function of lymph vesscJ transplants was 
evalualed by measuring the intra[ymphal ic end pressure. 
We were able to prepare Iymph eolleetors of the 
superficial medial system for the full lengt h of the 
left thigh. Two eolleetors with a length of 25 em 
were transposed to the right side via the symph ysis 
(Fig. 8). At the right grain , two end-to-e nd anasto-
moses with a superficial und a dee p Iymph vesscl of 
the edematous leg were performed using the te n-
sion-free anastomosing technique. Within onc 
week, the diffe renee in the eireumfe renec war rc-
dueed 10 a maximum of I em. After a pefiod of over 
9 months, this resull remains unehanged. Tcchne-
tium-99m-albumin (Tecernin) was injected in the 
right foot to establish pateney. Afterwards, groin 
aetivity showed a rise in both grains with a dclay in 
the left grain . After massage of thc affeeted leg, an 
extra rise eould be deteeted in both groins (Table I). 
With the aid of the gamma earnera, the path of the 
transplants eould be fo llowed to the sy mphysis. 
There is an overlapping with the aeti vity in the 
bladde r (Fig. 9) . 
, 
j ,: 
Fig. 8. Lymph collectors of the lef! thigh lransposcd via 
Ihe symphysis. 
The seeond palient was a 57-year-old female. 
Two years ago, an anal eare inoma was treated by 
abdominoperineaJ cxtirpation of thc rectum with 
eonseeuli ve Iymph node extirpation at both groins, 
followed by radiat ion Iherapy. A progressive Iym-
phedema developed over a 6-rnonth period . Scintis-
eans with Technetium-99m-sulfur-colloid (Lym-
phoszint) showed no Iymphat ie flow 10 the iliac 
nodes in the fight edematous leg. On the left side , 
there was no signifieant defeel in Iymph tmnsporta-
tion. Surgicall y, two Iymph eolleetors were trans-
posed via the sy mphysis and anastomosed end-to-
end with the superfieia l and deep Iymphatic system. 
Within 3 wecks, the eircumferenees we re markedl y 
reduced especiall y at the lowe r leg (Table 2). This 
time, seinti seans showed a quick flow of the Iymph 
out of the ext remit y. 
Diseussion 
The restoration of a sufficie nt transporting eapacity 
ofthe Iymphatie system by transplant ation of lymph 
vessels was experimentall y aceompli shed in the 
most scvere form of Iymphedema. After the total 
bloekage of the Iymphatic system, a maJignant 
Iymphedema developed. Untreated, thi s leads to 
death from profuse loss of proteins Ihrough the 
skin . Our expcrienees with 5 dogs eorrespond to 
that of C10dius [5]. In elini cal situations, the defi-
cieney of transporting capacity is less scvere than 
that of this experimental model. 
Anothcr important aspect is the devclopment of 
Table I. Half-life period corrected simultaneous rneasure rnent s of (he aclivilY in the right and left groin after suhcutaneous 
application of Tccernin in the first patient 's righl foot [t (counts/sec)l. 
Measurernent point (min) 
Right groin 
Left groin 
'0 
200 
20 
100 
260 
100 
150 1 
240 
140 
IMassage of Ihe right lower leg was perforrncd after mcasurerncnt at 150 rnin. 
200 
280 
300 
230 
270 
330 
250 
260 
280 
Fig. 9. Lymphulic scinliscu n showing Ihe course of Ihe 
trunsplants to the symphysis. 
an infect ion and a scleros is of thc edcmatous limb 
with a thicke ning of the basal membrane of the 
Iymph capillaries a nd an accumulat ion of collagen 
fibers around the Iymph vcsscl [6]. For a full 
rehabilitation by Iymph vcssel transplantation, il is 
thercforc desirable 10 petform the operation in stage 
1 of the Iymphcdema. As ct inical experience shows, 
there is also Iymph How alo ng fi brot ic Iymph ves-
sels. Moreover. macrophages are able to desl roy 
the intcrstitial proteins [7, 81. Thereforc, a diminu-
tion of the fibrosis might be possible after improve-
ment of the Iymph ftow in stage 2. 
An alternate mcthod to the microsurgical Iymph 
vcssel t ransplantat ion is thc crcal ion of mi cro-
Iymphove nous shunt s [9--11]. Since in edematous 
limbs spontaneous anasto moses have bcen seen 
[1 2J. lymphovenous anastomoses are onl y a quanti-
tative improve ment of a compensation mechanism 
that is obv iously working insufficientl y. 
The vcnous peripheral pressure is higher tha n the 
intralymphat ic pressure, at least at rest [13]. Opera-
tions dealing o nl y with thc Iymphatic system have 
the advantage that thc ri sk of a thrombosis is 
dimini shed by the low coagulation parameters of 
thc Iymph [14]. 
The transplantation of Iymph vcssel s eould also 
be added to a resectio nal procedure for trcating 
stage 3 Iymphedc ma. Recurrcnt cpi sodes 115] may 
be avoided by thc improvemcnt in thc transporting 
capacit y of the Iymphatic system. 
Acknowledgments 
We thank lutta Krumbach for her cxce llenltechni-
cal assistance . The investigation was generously 
supported by a gra nt of the VW Foundatio n. 
References 
I . Földi, M. : Physiology and palhophysiology ofl ymph· 
flow. In Lymphedema. L. Clodius. cdi tor. Stullgart, 
Georg Thieme Publishers, 1977, pp. i- I i 
2. Clodius, L. , Wirth , W.: A new experimental model 
for ehronic lymphedema ofthe extremities. Chir Plast 
(Ber!. ) 2: 11 5, 1974 
3. Baumeister. R.G.H., Seife rt, J. , Wiebeeke. B. : 
T ransplantation of lymph vessels on rats as weil as a 
fi rs t therapcutic applieat io n on the c,,- perimental lym· 
phedcma of thc dog. Eur. Surg. Res. I1[Suppl. 2J:7, 
1980 
4. Olszewski , W.l. : Colleetion and physiological mea-
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man. Lymphology 10: 137, 1977 
5. Clodius, L. : The experimental basis for the surgieal 
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6. Olszewski W.: On the palhomechanism of dcvelop-
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1973 
7. Casley-Smith, J .R.: A fine structural study of the 
removal of the eßectiveness of benzo-pyrone treat-
ment ofl ymphedema by the destructio n ofthe mac ro· 
phages by silica. Br. J. Exp. Pat hol. 59(2): 116, 1978 
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venous shunts for decompression of secondary Iym-
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Table 2. Prcoperative and postoperative circu mfe renees of the surgically treatcd right leg compared to those of thc 
untreated Icft leg in the sccond pat icnt . 
Thigh 
Knee 
Lower leg 
Ankle 
Metatarsus 
Left circumfcrences 
(cm) 
57 
41.5 
38.0 
22.0 
23 .0 
Right eircumferences (em) 
Preoperative 
63.5 
46.0 
42.0 
26.0 
25.0 
Postoperative 
61.5 
42 .5 
39.0 
23.0 
23.0 
lO. O'Brie n. H.M., Shafiroft', B.B.: Microlymphatico-
venous and resectional surgery in obstructive Iym-
phedema, World J . Surg. 3:3. 1979 
11 . Degni , M.: New technique oflymphatic-venous anas-
tomosis for the treatment of Iymphedema. 1. Cardio-
vasc . Surg. (Torino) {9(5) :577, 1978 
12. Edwards, J .M .. Kinmonth , J.B .: Lymphovenous 
shunt in man. Br. Med. J. 4:579, 1969 
13. Yamada. Y.: Thc study of lymphatic venous anasto-
mosis in Iymphcdcma. Nagoya J . Med . 31: 1. 1%9 
14. Yoffey. J .M. , Courtice. F.C.: Lymphat ics. Lymph 
and the Lymphomyeloid Complex. London-New 
York , Academic Press. 1970 
15, Clodius. L. : In vited commentary on " Microlympha-
ticovenous and resectional surgery in obSl ruclivc 
Iymphedema," World J, Surg. 3: 121, 1979 


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Experimental Basis and First Application of CLinical Lymphvessel-Transplantation of Secondary Lamphedema

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