Long-term outcome of open surgery in CVI patients concerning postoperative complications,perioperative hemodynamics and clinical efficacy,Part II 1

Abstract

BACKGROUND:

Chronic venous disease (CVD) is extremely common worldwide with prevalence increasing with age. It is associated with a reduced quality of life, particularly in relation to pain, physical function and mobility. Symptomatic chronic venous insufficiency (CVI) with venous ulcer at its’ endpoint, indicates interventional surgery to cure venous reflux therewith promoting wound healing and preventing recurrence. In this retrospective, single-centre, consecutive case-control study in a single patient population of a university clinic in northern Germany a holistic evaluation of varicose vein surgeries has been undertaken. Part I covered postoperative complications in relation to co-morbidities, co-medication and clinical presentation. Part II of this article presents now the hemodynamic results in relation to the perioperative evolution of CVI specific symptoms.

METHODS:

Records of n = 429 (467 extremities) patients from 2009-2013 treated with open surgery were analysed with regards to perioperative hemodynamics. Evolution of CVI symptomology was accessed postoperatively with the help of a questionnaire and patient records in the case of complication development. Venous hemodynamics was analysed in the whole patient population and with regards to complication subgroups: no events (NE), neglectable adverse events (NAE) and non-neglectable adverse events (NNAE).

RESULTS:

Postoperatively, patients’ CVI-symptoms like pain (p < 0.001), swelling (p < 0.001) and itching (p = 0.003) significantly improved. The venous refill time and venous pump capacity improved significantly after open vein surgery (p < 0.05). Regardless of the development of postoperative complications there was a significant improvement of venous function at 6 weeks- and one-year postoperative in follow-up (p < 0.05). Symptom regression was strongly correlated with hemodynamic improvement.

CONCLUSION:

A significant improvement of patients’ symptoms was achieved by means of open-surgery, regardless of postoperative complication development. This was in accordance with the improvement of venous hemodynamics. A strong correlation between symptom regression and improvement in venous hemodynamics could be proven.

Keywords

Perioperative hemodynamics perioperative symptomology digital photoplethysmography

1 Background

Over the last decades the armament of a phlebologist for the treatment of a chronic venous insufficiency (CVI) has been broadened by the introduction of minimally invasive procedures like sclerotherapy and various endovenous ablation techniques [1]. Though, the overall incidence of venous disease in general population is very high [2 –5] (76.1 per 100,000 person-years) [3], it is characterised by a low mortality rate. Nonetheless, symptomatic CVI is associated with a high level of suffering [6 –8]. Further, the technological advancements nowadays lead to an increasing sophistication and self-education of our patients concerning treatment options which is accompanied by an increase in law-suits [9, 10]. Hence, it is crucial for the treating physician nowadays to understand the risks and benefits associated with each technique.

In the case of a stripping operation a comprehensive outcome evaluation for the treatment of a symptomatic venous disease necessitates not only investigating postoperative complication rates, like in Part I of this publication, but also the perioperative evaluation of patients’ symptoms and hemodynamics of leg veins. Like any other chronic disease, a symptomatic CVI has proven to negatively impact patients’ quality of life [11].

Sadly, a good comparison is hindered by the high variety of outcome measures in studies including the evaluation of patients’ symptoms [12], recurrence rate [13, 14], hemodynamics [15 –17] as well as quality of life [18, 19].

Therefore, the principal objective of this part of the study was to evaluate the influence of vein stripping on the evolution of CVI-symptoms and the perioperative venous hemodynamics. Additionally, we wanted to see whether there is a correlation between the improvement of venous function and regression of CVI specific symptoms.

2 Material/Patients

Patients undergoing surgical treatment of symptomatic chronic venous disease (CVD) in a single unit from 01.01.2009–31.12.2013, in the dermatological department in Greifswald, Germany were evaluated with regards to perioperative venous hemodynamics. To investigate the development of perioperative symptoms every patient additionally received a postally sent questionnaire in 2015. Further, perioperative records were evaluated with regards to CVI symptomology in the case of complication development.

3 Methods

3.1 Evaluation of venous function

For assessment of venous function every patient received preoperatively, six-weeks- as well as one-year postoperatively a digital photoelectric plethysmography (D-PPG) examination (ELCAT Vasoquant VQ1000; ELCAT Medical Systems, Wolframhausen, Germany). The venous function of every patient was evaluated according to a standardized diagnostic regiment as follows:

At constant room temperature between 20°C– 24°C the venous function test was performed in sitting position with the knees bent to 110°. The D-PPG sensor was placed pressure free on healthy skin at the medial aspect of the lower leg, 10 cm above the malleolus medialis. Every patient performed 10 dorsoflexions of the foot. The venous refill time (in seconds) and venous pump capacity (in %) were evaluated with an infrared light emitting diode (PPG electrode) and a photosensor. The venous refill time evaluated the time of total refill of the dermal plexus after blood ejection and was classified as follows:

>25s = normal venous function

24–20s = pathological venous function grade

19–10s = pathological venous function grade II

<10s = greaterthan pathological venous function grade III

Venous pump capacity evaluated the maximal ejection capacity by initiating the muscle pump function of the lower leg and was defined as follows:

≥3% = normal

<3% = greaterthan pathological

If pathological, a tourniquet, simulating a stripping operation, was applied below the knee and inflated to 80 mmHg to compress the small saphenous vein. In order to compress the great saphenous vein, the tourniquet was applied to the thigh. The improvement of the venous refill time and venous pump capacity indicated a pathology of the epifascial system. A further decline in venous refill time (in seconds) or venous pump capacity (in%) indicates a pathology of the subfascial system or originating from incompetent perforating veins and/or side branches which was further analysed by ultrasonography.

3.2 Evaluation of patients’ symptoms over time

The evolution of patients CVI-specific symptoms was accessed via a postal interview consisting of 33 questions. With regards to CVI-related symptoms this questionnaire was based on the Tuebingen life-quality questionnaire [20] and was sent to the patients surveying pre- and postoperative symptoms and their evolution over the course of treatment in 2015. After 6 months, if an answer was not received the patient was reminded by phone call. If appropriate, every question included a scale to grade e.g. the severity of symptoms or the health status of the leg (Fig. 1).

Fig.1

Study design: In total 429 patients (467 extremities) were included in this retrospective study. In 130 extremities postoperative complications could be detected. 20 extremities received a ligation of a perforating vein. 120 extremities were treated with a miniphlebectomy and 278 and 49 extremities received a fast ligation and stripping of the great saphenous vein and small saphenous vein respectively. Over a postoperative period of one year every patient received regular follow ups (1d post-op 405 extremities, 10 days post-op 393 extremities, 6 weeks post-op 353 extremities and one-year post op 268 extremities were visited). Every patient received an additional questionnaire concerning CVI related symptoms (preoperatively, postoperatively and later in time). Abbreviations: MP: miniphlebectomy; GSV: great saphenous vein; SSV: small saphenous vein; PF: perforator ligation; DPPG: digital photoplethysmography examination; US: ultrasound examination.

3.3 Statistical analysis

Pre- and postoperative results (venous refilling time and ejection fraction) of digital photoplethysmography (DPPG) as well as answers of symptoms-related questionnaires were analysed with the software R 3.5.0 and R Studio (Open source Licence). DPPG was analysed with one-way ANOVA (group classification according to no events, neglectable events, non-neglectable events as the factor) and paired t-test within groups. The data mining from textual answers was done with r-package stringi. The correlation of answers to other variables was examined with Chi-square test or fishers’s test or correlation test. P < 0.05 was deemed as significant. The correlation analysis between symptoms and venous refill time was performed with the cor function of the software R. As descriptive statistics we used mean, SD, Min- Max, Median, Graphics Boxplots and Line diagrams and scatter plots.

4 Results

4.1 Postoperative venous function

All patients undergoing an open surgery of the great or small saphenous vein were invited to a six-weeks and one-year follow-up post-procedure. Here the patients received a venous function test via DPPG as described above and a duplex ultrasound evaluating the venous reflux. The follow up of patients receiving a miniphlebectomy depended on the extend of operation.

For evaluation of venous function via DPPG, in total, 350 extremities were included. The results of 117 extremities were excluded due to missing preoperative DPPG data. Of these extremities 134 were lost to the 6-weeks follow up either due to missing DPPG-function test or the patient not attending the follow-up visit. 168 extremities were examined 1 year postoperatively.

In general, postoperative venous refill-time (18 sec. (SD±11,67) pre-op vs. 31 sec. (SD±12,12) 6 weeks post-op) and venous pump-capacity (3,6% (SD±4,0) pre-op vs. 5,5% (SD±3,6) 6 weeks post-op) significantly improved in the whole cohort (p = 0.001, p = 0.001 respectively) and was stable at one year follow up (refill time: 31 sec. (SD±12,12) 6 weeks post-op vs. 31,9 (SD±11,7) 1 year; venous pump-capacity: 3,6% (SD±4,0) 6 weeks post-op vs. 5,2% (SD±3,3) 1 year post-op; p > 0.05) (Fig. 2). The development of postoperative complications had no influence on the overall venous function (p > 0.05) after surgery and there were no significant differences in the postoperative venous function of the three patient subgroups: no-events, neglectable-events and non-neglectable events (Fig. 3).

Fig.2

Venous function in whole patient population: There is a statistically significant improvement of venous refill time (RT) six weeks postoperatively (p = 0.001). At one-year follow-up the venous function is at a stable level (p = 0.104). The venous pump capacity (in%) also shows a significant improvement 6 week (p = 0.001) postoperatively with no significant deterioration at one-year follow-up (p = 0.197). Abbreviations: RT: refill time, post-op: postoperatively.

Fig.3

Venous function comparison in subgroups (no E.: no events (NE), negl. E.: neglectable adverse events (NAE), non-negl. E: non-neglectable adverse events (NNAE)). The development of postoperative complications did not show to impact venous refill time (RT) and venous pump capacity (in%) in the neglectable events and non-neglectable events subgroups in comparison to the subgroup of no events (p > 0.05). Abbreviations: no. E.: no events (NE); negl. E.: neglectable adverse events (NAE); non-negl. E: non-neglectable adverse events (NNAE).

4.2 Evaluation of patients’ perioperative symptoms

Questionnaires were sent to all patients treated with open venous surgery from 2009–2013. 167 patients (38,92%) returned an answered questionnaire. After exclusion of missing data, the answered questionnaires of 135 (31,46%) patients were enrolled and finally formed the population for the evaluation of CVI-related symptoms. Twelve of these patients received a treatment of both extremities (n = 147 extremities). In total 120 patients of this population had no postoperative complications, whereas 9 patients had neglectable adverse events (n = 5 postoperative dysesthesia, n = 2 prolonged postoperative pain; n = 1 bulla formation at suture site, n = 1 HIT) and 6 patients non-neglectable adverse events (n = 3 postoperative wound infection, n = 2 postoperative thrombotic event, n = 1 postoperative bleeding). Patients developing postoperative complications received a close follow-up with documentation of evolution of symptomology, these data were also included this assessment (n = 114). There were no significant differences concerning the demographic data, clinical grade and treatment-type between patients who answered the questionnaire and patients who did not.

4.2.1 Perioperative limb symptoms and venous ulcer

Overall, 105 (50%) patients of the included patients (n = 210) had preoperative pain/discomfort in the treated extremity. In the immediate post-operative period this symptom reduced by 37,15% (n = 66). Over the course of time pain improved significantly (p < 0.001) and only 15 (7,61%) patients had pain at the time of survey. CVI-related oedema was present in 149 (70,95%) patients before operation. This symptom also improved significantly after surgical therapy (p < 0.001), only 62 (29,52%) patients had oedema immediately postoperative and 28 (20,74%) patients had a swelling of the treated leg later in time (p = 0.0034). Itching also significantly improved after surgery (p = 0.003) (Fig. 4, Table 1). Although statistically not significant a trend in ulcer healing can be seen (venous ulcer pre-operative n = 17 and later-on n = 5 p = 0.152). Regardless of the development of postoperative complications (NAE, NNAE) patients’ symptoms (pain, swelling) improved significantly (p < 0.001). In total 66,7% of patients answering the questionnaire stated a good leg health postoperatively.

Table 1
Evolution of typical venous symptoms (pain, swelling), venous ulcer and the venous function (V0 and T0) over the course of time. There is a statistically significant improvement of venous symptoms (pain, swelling) and venous function (V0, T0) after open surgery. Though not statistically significant an overall all reduction in total numbers of venous ulcer can be seen. Abbreviations: DPPG: digital photoplethysmography examination; T0: Venous refill time; V0: Venous pump capacity; SD standard deviation

Characteristic Pre-operative Post-operative Later p-Value

Pain n/ total (%) 105/210 (50) 66/210 (31) 15/197 (8) <0.001

Swelling n/total (%) 149/210 (71) 62/210 (30) 13/197 (8) <0.001

Venous ulcer n/total (%) 17/122 (14) 13/120 (11) 5/107 (5) 0.152

DPPG- T0 mean (SD) 18,0 (11.6) 31,9 (12.2) 32,3 (11.4) <0.001 ^×

DPPG- V0 mean (SD) 3,6 (4.0) 5,5 (3.6) 5,2 (2.9) <0.001 ^×

Characteristic	Pre-operative	Post-operative	Later	p-Value
Pain n/ total (%)	105/210 (50)	66/210 (31)	15/197 (8)	<0.001
Swelling n/total (%)	149/210 (71)	62/210 (30)	13/197 (8)	<0.001
Venous ulcer n/total (%)	17/122 (14)	13/120 (11)	5/107 (5)	0.152
DPPG- T0 mean (SD)	18,0 (11.6)	31,9 (12.2)	32,3 (11.4)	<0.001 ^×
DPPG- V0 mean (SD)	3,6 (4.0)	5,5 (3.6)	5,2 (2.9)	<0.001 ^×

^×p-Value refers to the pre- and post-operative venous function values.

4.3 Further analysis and correlations

Symptoms were present in all clinical CEAP-classes and no significant correlation between the number of symptoms and the CEAP-class (C- for clinical) of the reviewing clinician (p = 0.255) was found. CVI specific symptoms were likewise present in low and high duplex sonographic Hach grade. The number of symptoms was independent of the length of venous reflux represented by duplex sonographic Hach grade (p = 0.474).

Fig.4

Evolution of venous symptoms: The typical venous symptoms pain/discomfort (p = 0.0003), swelling (p = 0.0034), itching (p = 0.0030) improve significantly after open surgery. Abbreviations: pre-op: preoperatively; post-op: postoperatively.

Analysed data concerning venous symptoms (pain and swelling) and venous function (refill time) showed a strong correlation between reduction of symptoms and improvement of venous refill time in all patients regardless of postoperative complication development (neglectable adverse events (NAE) and non-neglectable adverse events (NNAE): pain: rho = 0.50; CI = [0.40, 0.60]; p = 0.000063; swelling: rho = 0.48; CI = [0.37, 0.58] p = 0.000006 no events (NE): pain: rho = 0.45; CI = [0.30, 0.58] p = 0.027264; swelling: rho = 0.44; CI = [0.29, 0.57]; p = 0.007662) (Fig. 5 and Fig. 6).

Fig.5

Correlation between pain (severity of pain 0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain) and venous refill time (RT) in patients with and without complication development. Abbreviations: RT: refill time, s: seconds; pre: preoperative: post: postoperative; later: at time of questionnaire/last follow-up of patients with complications.

Fig.6

Correlation between swelling (severity of swelling: 0- no swelling, 1- mild swelling, 2- moderate swelling, 3- severe swelling) and venous refill time (RT) in patients with and without complication development. Abbreviations: RT: refill time; s: seconds; pre: preoperative; post: postoperative; later: at time of questionnaire/last follow-up of patients with complications.

5 Discussion

Chronic venous insufficiency is a significant cause of morbidity in western societies [21, 22] consuming 1–3% of health care expenditures [23 –25]. Several studies have proven that patients’ symptoms rather than the presence of varicose veins itself or clinical grade of chronic venous insufficiency [4, 11] show to effect patients’ quality of life [6]. Further, the Edinburgh vein study showed a poor correlation between patient stated symptoms, CEAP clinical grade and duplexsonographic detected venous reflux [26 –28]. Keeping this in mind, the recommendations of the National Institute for Health and Clinical Excellence (NICE) for referral of varicose vein treatment including not only CVI related complications (thrombophlebitis, varicose vein bleeding, venous ulcer or trophic skin changes) but also CVI symptoms are only consequent [29].

With this background it is only coherent to investigate not only perioperative symptom development but also the evolution of venous hemodynamics. Further we wanted to see whether there is a correlation between improvement of venous symptoms and hemodynamics.

Like Campbell and co-workers we could show a statistically significant improvement of CVI related symptoms [30] like pain/discomfort (p < 0.001), swelling (p < 0.001) and itching (p = 0.003). Though the subgroup is too small for a robust statistical analysis one could see a definite ulcer healing in 64,7% of patients after one year and a healing tendency in the remaining 35,3%. These findings are satisfactory as venous ulcer patients are known to have low quality of life with regards to emotional and mental aspects [31]. Further we could proof that the long-term outcome in patients developing postoperative complications (n = 64 NE and n = 66 NNE) was not affected.

Additionally, we found that there was no correlation between the presence of CVI symptoms (p > 0.05) and clinical class of disease. This is in accordance with Darvall et al who stated that patients symptoms independently affect patients quality of life [6]. Regardless of the clinical presentation of disease patient’s symptoms should also weigh into the decision making for or against treatment. Though being beyond the scope of the present study Sitharan et al clearly depicted twice the reported prevalence of depression in late-stage CVI disease (C5-C6-CEAP Classification) [7] in comparison to general population. This is in line with depression rates in other chronically ill patients [7] These findings show the implications of venous disease proving it not being a cosmetic problem as perceived by many people [8].

The pre- and postoperative venous function with DPPG has only undergone limited investigation so far. In accordance to Strölin et al we could show a significant improvement of postoperative venous hemodynamics and a close correlation with improvement of venous symptoms [32].

6 Limitations

The results of the present study should be evaluated in the light of several limitations with regards to patient stated symptoms.

176 patients (38,92%) less than 50% of the treated patients answered the questionnaire. Therefore, we nowadays established that every patient attending a postoperative follow-up visit answers a standardised questionnaire to omit this problem in future.

The retrospective nature poses a limitation as the memory concerning pre- and postoperative symptoms is influenced by emotional factors which can either accentuate them negatively or reduce them depending on the time elapsed and experience connected with the CVI and therefore reduce the reliability of the answers.

7 Conclusion

Conflict of interest

None.

Funding

None.

References

McDaniel

, Nehler

, Santilli

, et al.Extended outcome assessment in the care of vascular diseases: Revising the paradigm for the 21st century. J Vasc Surg. 2000;2(6):1239–50.

Park

, Kwon

, Eom

, Lee

Prospective nonrandomized comparison of quality of life and recurrence between high ligation and stripping and radiofrequency ablation for varicose veins. J Korean Surg Soc. 2013;84(1):48–56.

Heit

, Rooke

, Silverstein

, et al.Trends in the incidence of venous stasis syndrome and venous ulcer: A 25-year population-based study. J Vasc Surg. 2001;33(5):1022–7.

Smith

, Garratt

, Guest

, Greenhalgh

, Davies

Evaluating and improving health-related quality of life in patients with varicose veins. J Vasc Surg. 1999;30(4):710–9.

Uema

, Dezotti

NRA

, Joviliano

, Dalio

, Moriya

, Piccinato

A prospective study of venous hemodynamics and quality of live at least five years after varicose vein stripping. Acta Cir Bras. 2013;28(11):794–9.

Darvall

KAL

, Bate

, Adam

, Bradbury

Generic health-related quality of life is significantly worse in varicose vein patients with lower limb symptoms independent of CEAP clinical grade. Eur J Vasc Endovasc Surg. 2012;44(3):341–4.

Sritharan

, Lane

TRA

, Davies

The Burden of Depression in Patients with Symptomatic Varicose Veins.

Kaplan

, Criqui

, Denenberg

, Bergan

, Fronek

Quality of life in patients with chronic venous disease: San Diego population study. J Vasc Surg. 2003;37(5):1047–53.

Critchley

, Handa

, Maw

, Harvey

, Corbett

Complications of varicose vein surgery. Ann R Coll Surg Engl. 1997;79(2):105–10.

10.

Sudip

Complaints and litigation following varicose vein surgery. Clinical Risk. 2005;11(6):221–4.

11.

Kurz

, Lamping

, Kahn

, et al.Do varicose veins affect quality of life? Results of an international population-based study. J Vasc Surg. 2001;34(4):641–8.

12.

Garratt

, Ruta

, Abdalla

, Russell

Responsiveness of the SF-36 and a condition-specific measure of health for patients with varicose veins. Quality of Life Research. 1996;5(2):223–34.

13.

Papapostolou

, Altenkämper

, Bernheim

, et al.The LaVaCro-Study: Long-term results following saphenofemoral ligation and stripping of the great saphenous vein. Phlebologie. 2013;42(5):253–60.

14.

Rass

, Frings

, Glowacki

, Gräber

, Tilgen

, Vogt

Same site recurrence is more frequent after endovenous laser ablation compared with high ligation and stripping of the great saphenous vein: 5 year results of a randomized clinical trial (RELACS Study). Eur J Vasc Endovasc Surg. 2015;50(5):648–56.

15.

Kim

I-H

, Joh

J-H

, Kim

D-I

Venous hemodynamic changes in the surgical treatment of primary varicose vein of the lower limbs. Yonsei Med J. 2004;45(4):577–83.

16.

Park

U-J

, Yun

W-S

, Lee

K-B

, et al.Analysis of the postoperative hemodynamic changes in varicose vein surgery using air plethysmography. J Vasc Surg. 2010;51(3):634–8.

17.

Ik Kim

, Boong Lee

, Bergan

Venous hemodynamic changes after external banding valvuloplasty with varicosectomy in the treatment of primary varicose veins. J Cardiovasc Surg (Torino). 1999;40(4):567–70.

18.

MacKenzie

, Lee

, Paisley

, et al.Patient, operative, and surgeon factors that influence the effect of superficial venous surgery on disease-specific quality of life. J Vasc Surg. 2002;36(5):896–902.

19.

MacKenzie

, Paisley

, Allan

, Lee

, Ruckley

, Bradbury

The effect of long saphenous vein stripping on quality of life. J Vasc Surg. 2002;35(6):1197–203.

20.

Klyscz

, Jünger

, Schanz

, Janz

, Rassner

, Kohnen

Lebensqualität bei chronisch venöser Insuffizienz (CVI). Der Hautarzt. 1998;49(5):372–81.

21.

Beebe-Dimmer

, Pfeifer

, Engle

, Schottenfeld

The epidemiology of chronic venous insufficiency and varicose veins. Ann Epidemiol. 2005;15(3):175–84.

22.

Robertson

, Yeoh

, Kolbach

Non-pharmacological interventions for preventing venous insufficiency in a standing worker population. Cochrane Database Syst Rev. 2013;10:CD006345.

23.

Ruckley

Socioeconomic Impact of Chronic Venous Insufficiency and Leg Ulcers.

24.

Lafuma

, Fagnani

, Peltier-Pujol

, Rauss

Venous disease in France: An unrecognized public health problem. J Mal Vasc. 1994;19(3):185–9.

25.

Evans

, Fowkes

, Ruckley

, Lee

Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. Journal of Epidemiology and Community Health. 1999;53(3):149.

26.

Bradbury

, Evans

, Allan

, Lee

, Ruckley

, Fowkes

The relationship between lower limb symptoms and superficial and deep venous reflux on duplex ultrasonography: The Edinburgh Vein Study. J Vasc Surg. 2000;32(5):921–31.

27.

Ruckley

, Evans

, Allan

, Lee

, Fowkes

FGR

Chronic venous insufficiency: Clinical and duplex correlations. The Edinburgh Vein Study of venous disorders in the general population. J Vasc Surg. 2002;36(3):520–5.

28.

Bradbury

, Evans

, Allan

, Lee

, Ruckley

, Fowkes

What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey. BMJ. 1999;318(7180):353–6.

29.

National Institute for Clinical Excellence. Varicose veins in the legs: The diagnosis and management of varicose veins2013.

30.

Campbell

, Decaluwe

, Boecxstaens

, et al.The symptoms of varicose veins: Difficult to determine and difficult to study. Eur J Vasc Endovasc Surg. 2007;34(6):741–4.

31.

Dias

TYAF

, Costa

IKF

, Melo

MDM

, Torres

SMDSGSDO

, Maia

EMC

, Torres

GDV

Quality of life assessment of patients with and without venous ulcer. Rev Latino-Am. Enfermagem. 2014;22(4):576–81.

32.

Strölin

, Häfner

H-M

, Rühle

, et al.Venous surgery for the treatment of chronic venous insufficiency with respect to global venous haemodynamics and clinical symptoms. Phlebologie. 2009;38(01):26–32.