Objectives:Recurrent varicose veins may result from poor initial surgical technique or progression of varicosities in collateral veins. In some cases new veins may develop at the saphenofemoral junction (neovascularisation) and cause recurrent saphenofemoral incompetence. This was a histological study of recurrent varicose veins.Design:This clinicopathological study included 20 patients (median age 55 years) who had surgery for recurrent saphenofemoral incompetence.Materials and methods:A total of 28 legs had groin re-exploration with repeat flush saphenofemoral ligation. The venous tissue block from the saphenofemoral region (including the proximal thigh varicosity) was excised and orientated for histological analysis. Evidence of neovascularisation was sought using routine histological sections and S100 immunohistochemistry.Results:At operation, thin-walled, serpentine neovascular veins were detected clinically as the principal cause of recurrence in 19 groins. In five groins recurrence was due to a residual missed vein at the saphenofemoral junction, and in four recurrence was caused by cross groin collaterals. On histological sections, evidence of neovascularisation was present in 27 of 28 groins. In eight it co-existed with the veins missed at the original operation but it was the sole identified cause of recurrent saphenofemoral incompetence in 19 (68%) groins.Conclusions:Neovascularisation was the principal cause of recurrent saphenofemoral incompetence in this series

Davies, B.

Earnshaw, J.J.

Heather, B.P.

Nyamekye, I.

Shephard, N.A.

Elsevier - Publisher Connector 

Clinicopathological evidence that neovascularisation is a cause of recurrent varicose veins 

Eur J Vasc Endovasc Surg 15, 412-415 (1998) 
Clinicopathological Evidence That Neovascularisation is a Cause of 
Recurrent Varicose Veins* 
I. Nyamekye, N. A. Shephard% B. Davies, B. P. Heather and J. J. Earnshawt 
Gloucestershire Vascular Group and ~Department of Histopathology, Gloucestershire Royal Hospital, Gloucester, U.K. 
Objectives: Recurrent varicose veins may result Jarom poor initial surgical technique or progression of varicosities in 
collateral veins. In some cases new veins may develop at the saphenofemoraI junction (neovascularisation) and cause 
recurrent saphenofemoral incompetence. This was a histological study of recurrent varicose veins. 
Design: This clinicopathologicaI study included 20 patients (median age 55 years) who had surgery for recurrent 
saphenofemoral incompetence. 
Materials and methods: A total of 28 legs had groin re-exploration with repeat flush saphenofemoraI ligation. The 
venous tissue block from the saphenofemoral region (including the proximal thigh varicosity) was excised and orientated 
for histological analysis. Evidence of neovascularisation was sought using routine histological sections and $100 
immunohistochemistry. 
Results: At operation, thin-walled, serpentine neovascular veins were detected clinically as the principal cause of 
recurrence in 19 groins. In five groins recurrence was due to a residual missed vein at the saphenofemoral junction, and 
in four recurrence was caused by cross groin collaterals. On histological sections, evidence of neovascularisation was 
present in 27 of 28 groins. In eight it co-existed with the veins missed at the original operation but it was the sole 
identified cause of recurrent saphenofemoral incompetence in I9 (68%) groins. 
Conclusions: Neovascularisation was the principal cause of recurrent saphenofemoral incompetence in this series. 
Introduction 
Recurrent saphenofemoral incompetence, first re- 
ported by Langenbeck, 1 is the major cause of recurrent 
varicose veins, a-6 It is associated with persisting symp- 
toms and patient dissatisfaction a d represents a major 
drain on health care resources. The cause of recurrent 
incompetence at the saphenofemoral junction is con- 
troversial but most authors blame failure to perform 
adequate dissection of the saphenofemoral junction. 7'8"9 
In properly ligated groins varicosities may develop in 
pre-existing collateral veins. 1°-~3 The growth of new 
veins at the saphenofemoral junction (neo- 
vascularisation) which then connect with an existing 
long saphenous or other residual thigh vein has been 
suggested as another cause, but this remains con- 
troversial and is variably reported, a'7"14"I5'16 
Histological evidence for new vein formation has 
been provided by Glass, both experimentally and clin- 
ically, after simple interruption of the long saphenous 
* Presented atthe Vascular Surgical Society 1996. 
~-Please address all correspondence to: I. J. Earnshaw, Glou- 
cestershire Royal Hospital, Great Western Road, Gloucester GL1 
3NN, U.K. 
vein. 17'18 A previous prospective study from this unit 
identified neovascularisation as the principal cause 
of recurrent varicose veins. 16 The present study was 
designed to determine the significance of neo- 
vascularisation in recurrent saphenofemoral in- 
competence using clinical and histological ssessment. 
Materials and Methods 
Twenty patients (10 men) who had surgery for re- 
current varicose veins (eight bilateral) due to recurrent 
saphenofemoral incompetence w re studied. Their me- 
dian age was 55 years (range 36-83) and the median 
interval between initial and recurrent venous urgery 
was 11,5 years (range 3--46). At the original operation 
19 groins had saphenofemoral disconnection alone 
and nine had additional stripping of the long sa- 
phenous vein in the thigh. Recurrent saphenofemoral 
incompetence was diagnosed by clinical assessment 
including hand-held Doppler ultrasonography. Re- 
current saphenofemoral incompetence was diagnosed 
when calf squeeze and release resulted in significant 
reflux in the groin and in an accompanying thigh 
1078-5884/98/050412+04 $12.00/0 © 1998 W.B. Saunders Company Ltd. 
Neovascularisation and Recurrent Varicose Veins 413 
varicosity. In nine equivocal cases the diagnosis was 
confirmed using colour duplex imaging. 
At groin re-exploration a consultant vascular sur- 
geon made a clinical assessment of the cause of the 
recurrent veins in the course of performing repeat 
flush saphenofemoral disconnection. A block of tissue 
from the region of the saphenofemoral junction (in- 
cluding the proximal aspect of the main thigh var- 
icosity) was excised and orientated for histology using 
marker sutures. 
The tissue block was sectioned transversely at2 mm 
intervals. These ctions were orientated, processed 
through paraffin wax and sectioned at 4 g. The histo- 
logical sections were stained with haematoxylin and 
eosin, elastin van Geison and reticulin stains. Further 
histological sections were prepared for $100 immuno- 
histochemistry b routine streptavidin-biotin labelling 
and microwave antigen retrieval. The hypothesis of 
the study was that immature neovascular veins would 
be tortuous and thin-walled, and lack mural nerves 
on $100 staining. Similar sized normal veins were 
examined as controls using identical histological and 
immunohistochemical techniques. 
Fig. 1. A typical section of a "new vein". There is marked asymmetry 
with great variation ha the thickness ofthe media (H&E x 40). 
Results 
Preoperatively the diagnosis of recurrent sa- 
phenofemoral incompetence was made in 19 groins 
using hand-held Doppler ultrasonography. In nine 
legs which needed colour duplex imaging because of 
equivocal Doppler findings, all had recurrent sa- 
phenofemoral incompetence, three due to missed veins 
at the saphenofemoral junction and six due to neo- 
vascularisation alone. 
At operation, serpentine neovascular veins were the 
sole connection between a thigh varicosity and the 
common femoral vein in 19 groins. A residual vein 
missed at the previous operation was easily identified 
at the saphenofemoral junction in five groins. In four, 
small veins passed from the thigh, across the groin, 
towards the anterior abdominal wall. These have been 
termed cross groin collaterals. 7 
Histological analysis confirmed the presence of tor- 
tuous, thin-walled veins. They were less well struc- 
tured compared with normal veins of equivalent size. 
One noticeable pathological feature, typical of im- 
mature veins, was the asymmetry of the vein wall, 
especially the thickness of the media (Fig. 1). Normal 
small veins in control tissue from primary varicose 
veins, mesenteric veins and veins from breast issues 
(controls) all stained positive for mural nerves on S 
100 immunohistochemistry. In contrast, there was a 
Fig. 2. A normal control vein of equivalent size to the vein in Fig. 
1 demonstrating an intramural nerve. Neovascular veins lacked 
these structures ($100 immunohistochemistry x 200). 
complete absence of mural nerves in the neovascular 
veins (Fig. 2). 
Neovascularisation was present in the tissue 
bridging the common femoral vein and the recurrent 
thigh varicosity by histological criteria in 27 of 28 
groins examined. In 19 groins these were the sole 
connections but in eight groins the new veins coexisted 
with a missed vein atthe saphenofemoral junction or a 
cross groin collateral. In one groin, the saphenofemoral 
junction appeared previously untouched and there 
was no evidence of new vein formation. 
There was no significant difference in the interval 
between the first and second operations i  patients 
with neovascularisation c mpared with those who had 
a residual missed vein in addition (mean 13.7 and 14.3 
years, respectively.) 
Discussion 
Langenbeck 1 suggested that regeneration of the long 
saphenous vein at the site of transection could be 
Eur J Vasc Endovasc Surg Vol 15, May 1998 
414 I. Nyamekye et al. 
a cause of recurrent saphenofemoral incompetence. 
Although this was supported in an early report by 
Homans, 19 the majority of studies have, until recently, 
blamed inadequate surgery or expansion of collateral 
veins as the principal cause of recurrent sa- 
phenofemoral incompetence. 7'8q5'2° 
The phenomenon ofneovascularisation, initially ob- 
served in the rabbit ear chamber model 21'22'23 has re- 
cently been demonstrated after ligation of the rat 
femoral vein and after transection of the long sa- 
phenous vein in the lower part of the thigh in patients 
with varicose ulcers, aTas In the latter study new vein 
formation was demonstrated by angiography, surgical 
assessment and histological examination of excised 
tissue. 
The present study provides clinical and pathological 
evidence that neovascularisation ccurs in patients 
with recurrent saphenofemoral incompetence. Many 
of the patients previously had saphenofemoral dis- 
connection alone, whereas stripping of the long sa- 
phenous veins is presently recommended to reduce 
recurrence, as This may have influenced the incidence 
of neovascularisation. The clinical findings were sup- 
plemented by histology because imaging methods 
alone cannot reliably diagnose neovascularisation. Ma- 
ture neovascular veins can have luminal appearances 
indistinguishable from collateral veins on duplex im- 
aging. This failure to recognise neovascular veins may 
have led to an underestimate of their incidence using 
imaging studies. 7'24 Khaira et aI. reported a high in- 
cidence of neovascularisation; i  a study using colour 
duplex, 68% of recurrent saphenofemoral in- 
competence was due to neovascularisation35 
Histological analysis is a potentially more accurate 
for identifying neovascular veins although there is still 
no agreed efinition. Features een on routine staining 
such as vein tortuosity, small size and mural asym- 
metry have been used to diagnose neovascularisation 
but are suggestive rather than definitive. 17'~8 New veins 
lack the traversing intramural small nerves which are 
visible in mature veins. In this study the absence of 
intramural nerves on $100 stained sections provided 
further evidence that the veins have formed recently. 
It is accepted that negative demonstration of a focal 
structure, such as a mural nerve seen on $100 stained 
sections, is never entirely convincing but a more useful 
method for the diagnosis of neovascularisation is not 
yet available. 
It should come as no surprise that new veins form 
after saphenofemoral disconnection. Angiogenesis is 
a feature of all healing wounds. 25 Whether these early 
vessels go on to develop and cause clinical sa- 
phenofemoral recurrence probably depends on the 
presence of larger veins within reach of the developing 
vessels. Careful avulsion of all tributaries within the 
vicinity of the saphenofemoral junction during var- 
icose vein surgery might minimise saphenofemoral 
recurrence by reducing the chances of developing 
neovascular veins gaining communication with nearby 
tributaries or a residual ong saphenous vein. How- 
ever, this technique would have no effect if the new 
veins arise from the femoral vein close to the sa- 
phenofemoral junction. Further investigation of the 
source of neovascular veins is important. 
The present study provides clinical and histological 
evidence for neovascularisation as a major cause of 
recurrent saphenofemoral incompetence. The bio- 
logical basis of neovascularisation means that it is 
unlikely to be prevented by surgical technique alone. 
Barrier methods are presently being investigated but 
future research could be aimed at the use of growth 
factor inhibitors to reduce or prevent he process of 
angiogenesis. 
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Accepted 17 November 1997 
Eur J Vasc Endovasc Surg Vol 15, May 1998 


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Clinicopathological evidence that neovascularisation is a cause of recurrent varicose veins

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