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Pelvic congestion syndrome and left renal compression syndrome – clinical features and therapeutic approaches Christina Jeanneret1, Konstantin Beier2, Alexander von Weymarn3, and Jürg Traber4 1

Angiology, Med. University Hospital, Kantonsspital Baselland, Bruderholz, Switzerland Institute for Anatomy, Departement Biomedizin, Universität Basel, Switzerland 3 Radiology, Kantonsspital Frauenfeld, Frauenfeld, Switzerland 4 Clinic for Venous Diseases, Bellevue, Kreuzlingen, Switzerland 2

Summary: Knowledge of the anatomy of the pelvic, gonadal and renal veins is important to understand pelvic congestion syndrome (PCS) and left renal vein compression syndrome (LRCS), which is also known as the nutcracker syndrome. LRCS is related to PCS and to the presence of vulvar, vaginal and pudendal varicose veins. The diagnosis of the two syndromes is difficult, and usually achieved with CT- or phlebography. The gold standard is the intravenous pressure measurement using conventional phlebography. The definition of PCS is described as pelvic pain, aggravated in the standing position and lasting for more than 6 months. Pain in the left flank and microhaematuria is seen in patients with LRCS. Women with multiple pregnancies are at increased risk of developing varicose vein recurrences with pelvic drainage and ovarian vein reflux after crossectomy and stripping of the great saphenous vein. The therapeutic options are: conservative treatment (medroxyprogesteron) or interventional (coiling of the ovarian vein) or operative treatment (clipping of the ovarian vein). Controlled prospective trials are needed to find the best treatment. Key words: Gonadal veins, pelvic congestion syndrome, nutcracker syndrome, left renal vein compression syndrome, venous reflux ovarian veins, ovarian vein embolisation, ovarian vein clipping

Introduction Pelvic congestion syndrome is mainly described in women. The symptoms are difficult to quantify and the underlying pathophysiology is assumed to be ovarian vein reflux causing pudendal varicose veins. It might be associated with left renal compression syndrome. Pelvic congestion syndrome was first described in the 1950s by Taylor et al. [1] and left renal syndrome was first described in 1937 by Grant [2, 3]. De Schepper named it the “nutcrackersyndrome“ [4]. The superior mesenteric artery and aorta serve as the arms of a “nutcracker“, compressing the left renal vein. The symptoms of pelvic congestion include dysmenorrhoea, dysuria, dyspareunia, vulvar and pelvic varices as well as varicose veins of the lower extremities in females, and varicocele in males. Microscopic haematuria may occasionally occur. We describe the clinical, diagnostic and therapeutic options of pelvic congestion syndrome, including left renal vein compression syndrome.

Epidemiology Pelvic congestion syndrome has a prevalence of 15 % in women (18 – 50 years of age) in the United states [5]. In patients © 2016 Hogrefe

with painful pelvic varicose veins, pelvic congestion syndrome (PCS) can be responsible for the chronic pelvic pain. A 31 % incidence of PCS was found in a population of symptomatic women after evaluation with pelvic examination, laparoscopy, ultrasound or venography [6]. Belenky et al. found a 9.9 % prevalence of ovarian varices in 273 healthy female kidney donors. More than half of the patients (59 %) with ovarian varices have a pelvic congestion syndrome [7]. Fifty-nine percent of the patients reported pelvic pain retrospectively, suggesting that the majority of patients with ovarian vein reflux have pain symptoms.

Anatomy of the pelvic veins In the lesser basin, we find three foramina: the greater sciatic foramen, the lesser sciatic foramen and the obturator foramen. The following veins run through the various foramina: the superior gluteal veins through the greater sciatic foramen, the inferior gluteal veins and the internal pudendal vein through the lesser sciatic foramen, the obturatorian vein through the obturator foramen. The branches of the internal iliac vein drain through the openings (Figure 1), they form numerous anastomoses to the external iliac vein or the femoral vein. Vasa (2016), 45 (4), 275 – 282 DOI 10.1024/0301-1526/a000538

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The pelvic organs are drained by venous plexuses, which communicate with each other. In addition to the rectal venous plexus and the vesical plexus, we find prostatic venous plexus in men and uterine plexus and vaginal plexus in women, which are usually named uterovaginal plexus [8]. The rectal plexus connects the inferior mesenteric vein and portal vein with the internal iliac vein and the vena cava. Thus, the rectal plexus drains to both the portal vein (and thus to the liver) and the inferior vena cava. Increased venous pressure in the venous plexus can occur in cases with portal venous hypertension. In women, the rectal plexus has branches to the uterovaginal venous plexus and the vesical plexus. The uterovaginal plexus and the left ovarian vein play an important role in the pathophysiologic understanding of pelvic congestion syndrome and the “nutcracker syndrome“. The right gonadal vein (called ovarian vein in women and testicular vein in men) joins the inferior vena cava. The left gonadal vein drains into the left renal vein. The left renal vein (LRV) runs between the aorta and the superior mesenteric artery, which can cause compression of the LRV (Figure 2). If this compression causes a stasis in the left renal vein, left ovarian vein reflux can be seen. This entity is called “nutcracker phenomenon”. A rare anatomical variant is the so-called “posterior nutcracker phenomenon”, where the left renal vein is located behind the abdominal aorta and may be compressed between the aorta and the vertebral column [9].

Figure 1. Pelvic veins anatomy.

Venous valves of the pelvic veins, the gonadal veins and the renal veins Figure 2. Anatomy of the left renal vein and the aorto-mesenterial compression.

Table I. Clinical features of the pelvic congestion syndrome and the left renal vein compression syndrome Pelvic congestion syndrome19

Left renal compression syndrome26

Symptoms

Symptoms

Pelvic pain for > 6 months27 Pain worse while standing

Abdominal pain with nausea, vomiting (compression of the splanchnic veins)

Dyspareunia

Left flank pain

Dysmenorrhoea

Lower abdominal pain

Pain lumbar spine, rectal, labial Clinical signs

Intermittent haematuria

Venous drainage of the left and right gonadal vein is different: Because of the embryological development of the right gonadal vein, the blood is drained directly into the inferior vena cava, while the left gonadal vein joins the left renal vein. Vasa (2016), 45 (4), 275 – 282

Definition and clinical features of pelvic congestion syndrome and left renal compression syndrome

Clinical signs

Varicose veins vulva, vagina Microhaematuria

In recent publications, valves are described in the ovarian veins in 85 – 94 % of cases [10]. We find contradictory information about the existence of valves in the renal veins. Oleaga et al. showed valves in 5 of 22 left renal veins (phlebography study) and in 2 of 11 right renal veins. The valves were described as being located close to the junction between the renal vein and the inferior vena cava [11]. In a recent study, the phlebographically “detected” renal vein valves were not found on autopsy [12].

Pelvic congestion syndrome in women is defined as a chronic persistent pain in the pelvis, being present for more than 6 months, which is aggravated in the standing position. Dyspareunia, dysuria and haematuria may be present as well as left flank pain. These symptoms are associated with pelvine, vulvar and vaginal varicose veins [13, 14]. Pelvic congestion syndrome maybe associated with the left renal vein compression syndrome, also known as the “nutcracker phenomenon”. In Table I, the clinical features (signs and symptoms) of pelvic congestion syndrome and © 2016 Hogrefe

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Table II. Standardized questionnaire. Yes or No answers [15] 1. Do you suffer of pains at the lower limb in the standing and/or sitting position?

Yes

2. Do you suffer of leg swelling in the standing and/or sitting position?

Yes

3. Do you suffer of pain at the buttock and/or perineal region in the standing and/or sitting position?

Yes

4. Do you suffer of postcoital pain?

Yes

5. Do you suffer of urinary pain?

Yes

6. Is your pain related to the menstrual period?

Yes

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A score of 5 is predictive for pelvic congestion syndrome, each question answered with yes will result in 1 point

left renal vein compression syndrome are summarised. Pelvic congestion syndrome is associated with varicose veins of the pelvic and gonadal veins, while left renal vein compression may be associated with pelvic congestion syndrome. Asciutto et al. suggest a scoring system for the diagnosis of pelvic congestion syndrome; the questions are displayed in Table II. A score of 5 is predictive for pelvic congestion syndrome [15].

Diagnosis Venous reflux into the pelvic veins, the gonadal veins and the renal veins The parameter “venous reflux” is considered to be the standard testing of venous insufficiency in the leg veins. However, measurements of venous reflux in the renal, pelvic and gonadal veins is not feasible in a standardised way, using duplex sonography. On the one hand, we have no adequate provocation method, while on the other hand, gonadal veins are difficult to depict for flow measurements, and valves are not reliably detectable. It is recommended to evaluate the measurement of venous reflux in the gonadal veins by computed tomography and magnetic resonance imaging. Hiromura divides the spontaneous reflux in the left ovarian vein into grades 1, 2 and 3, as shown in Figure 3 [16]. The spectrum ranges from reflux in the ipsliateral ovarian vein to “cross-over” reflux into the right ovarian vein [16]. These studies were carried out in 151 asymptomatic women, using computed tomography. In addition to determination of the venous reflux, the vein diameters of the left ovarian veins were measured. Women with detectable venous reflux, showed significantly larger ovarian vein diameters (mean 8.3 ± 2.1 mm) than women without venous reflux (mean 4.9 ± 1.3 mm, p  5 mm). Twenty-one of these 30 patients also showed venous reflux in the proximal deep leg vein, most commonly in the femoral vein. Geier et al. showed different reflux patterns in patients with signs of pelvic venous incompetence, most often the right iliac internal vein

and the left ovarian vein were affected; in 51 % combined reflux in more than one pelvic vein was seen [21].

Ovarian vein reflux associated with varicose vein recurrence after great saphenous vein surgery: Own results In our own investigation, performed by our co-authors Jürg Traber and Alexander von Weymarn, female patients with recurrent thigh varicose veins after great saphenous vein (GSV) surgery were included. The inclusion process is summarised in Figure 4. In this observational study, 88 out of 527 (16.7 %) patients screened had a suspicion of ovarian

Figure 3. Ovarian vein reflux grading [16].

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C. Jeanneret et al.: Pelvic congestion syndrome and left renal compression syndrome, a review

vein reflux (OVR). OVR could be confirmed in 52 patients. The patient’s characteristics are displayed in Table V. Thigh varicose veins with a drainage pathway to the pelvic veins were found in 88 patients (16.7 %). Imaging studies (MRI 63, CT 17, catheter-directed venography 8) were carried out in 84 patients (4 patients refused diagnostic investigation). OVR was found in 52 cases (61.9 %). OVR was associated with varicose veins in the left leg in 35 cases, with bilateral varicose veins in 15 cases and varicose veins limited to the right side in 2 cases. The diameter of the refluxing ovarian veins showed a mean of 9.0 mm (n = 62, SD 2.1 mm, range 4 – 15 mm). Ovarian vein reflux was not detected in 32 patients (38.1 %). In these patients, mean ovarian vein diameter amounted to 5.3 mm (n = 8, SD 1.9 mm, range 2 – 7 mm). Comparison between the patients with ovarian vein reflux and patients without OVR is displayed in Table IV. The patients with OVR were significantly younger when they suffered from the recurrence of thigh varicose veins. The time to recurrence was shorter and these patients had more pregnancies in their history. Overall, 168 legs of the 84 patients with thigh varices were investigated for varicose veins and the following patterns were identified: Perineal, pudendal, and gluteal varices were found in 71 (42.3 %), 31 (18.5 %), and 7 (4.2 %) of the 168 legs, respectively. Inguino-femoral varicose veins were found in 34 of the 168 legs (20.2 %). Table VI summarises the findings, for the left and right leg in pa-

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Table V. Patients characteristics Patients with pelvic insufficiency

p-values

No OVR n=32

OVR n=52

No OVR vs OVR

Mean (SD)

Mean (SD)

Age at GSV operation (y)

35.3 (8.6)

32.7 (7.3)

0.1567

Age at recurrence (y)

51.2 (10.2)

42.8 (8.9)

0.0002

Time to recurrence (y)

15.9 (8.9)

10.3 (7.3)

0.0023

Height (cm)

169 (5.8)

168 (5.0)

0.7376

Weight (kg)

69.2 (16.9)

64.9 (10.0)

0.1485

BMI (kg/m2)

24.2 (5.4)

22.9 (3.4)

0.1676

No of pregnancies

2.5 (1.2)

3.1 (1.4)

0.0373

Abbr.: OVR = ovarian venous reflux, GSV = Great saphenous vein, BMI = body mass index, y = years

tients with and without OVR for the different recurrence patthways. The varices draining through the inguinal canal (inguino-femoral pattern) were clearly related to both a higher prevalence of the left leg and OVR.

Figure 4. Study design. Abbr.: SFJ = sapheno-femoral junction * suspicion if drainage pathway to the pelvic veins detected

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Table VI. Number of legs with and without ovarian reflux, according to the varicose vein recurrence pattern (n = 136 legs, 32 legs had other pathways)

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Right leg

Left leg

Pattern of varicose veins Number of legs

Ovarian vein reflux

No ovarian vein reflux

Ovarian vein reflux

No ovarian vein reflux

Perineal N = 71

22 (42 %)

16 (50 %)

22 (42 %)

11 (34 %)

Pudendal N = 31

10 (19 %)

9 (28 %)

4(13 %)

8 (15 %)

Inguinofemoral N = 34

4 (8 %)

8 (25 %)

18 (35 %)

4 (13 %)

Figure 5. Coiling of the left ovarian vein.

Vasa (2016), 45 (4), 275 – 282

Conclusion for the diagnostic procedures of the pelvic congestion syndrome and the left renal compression syndrome For the assessment of venous insufficiency of the pelvic and gonadal veins, there is currently no standardised procedure. The gold standard, the catheter-based intravenous pressure measurement in the different anatomical sections to be examined, is, although technically feasible, too expensive for routine use. Duplex sonography is not sensitive enough for the issue of venous insufficiency of the pelvic and gonadal veins and has been insufficiently evaluated to date. The variability of the venous valves and lack of opportunities for standardized provocation of the flap closure (such as Valsalva maneouvre or distal compression) complicate the interpretation duplex sonographic findings in the field of pelvic and gonadal veins. Possibly, the measurement of the vein diameters in standardised reference points could replace the catheterbased intravenous pressure measurement. This would have to be systematically evaluated in appropriate clinical trials first [22].

Figure 6. a) massive dilated insufficient left ovarian vein. b) 4 Hem-o-lock® Clips used to dissect the left ovarian vein.

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Table VII. Summary of treatment methods and outcome parameters Author

Year

Cases

Treatment methods

Follow up

Outcome

Scultetus [19]

2001

9

External stent (2), Internal stent (1) Gonadocaval bypass operation (3) No treatment (3)

36 months

Endpoint pain 90 % success endpoint microhaematuria 100 % success 1 partial thrombosed stent

Reed [31]

2009

23 13 female 10 male

Left renal vein transposition (11), 2 renal veins found occluded at operation No treatment (12)

26 months

8/10 patients with flank pain and 7/7 patients with haematuria resolved or improved

Wang [32]

2012

30, 2 female 28 male

Self expanding stents (14 mm diameter, 60 mm long)

12 months

2 stent migrations in vena cava 93 % resolved haematuria

Hocquelet [33]

2014

33 female

Embolisation all patients

26 months

20 patients are symptom-free, 1 technical failure

Therapy of the left renal compression syndrome (LRCS) Therapeutic concepts of the LRCS are mainly described in case reports. The two larger studies are summarised in Table VII. The main treatment option described is the left renal vein stenting; however, stent migration is described as an important side effect. In case reports, the operative treatments such as venous bypass graft (splenorenal or renocaval) and transposition of the left renal vein are described [23].

Therapeutic options of the pelvic congestion syndrome Medical therapy Reginald et al. treated 22 patients with PCS with 30 mg of medroxyprogesterone acetate (MPA) daily. Seventeen of the 22 patients reported a reduction of the pain score [24]. However, the often disturbing vulvar or vaginal varicose veins are not treated with hormone therapy. Soysal et al. tested medroxyprogesteron therapy (30 mg/day for 6 months) in 24 patients versus goserelin (3.6 mg/months for 6 months) in 23 patients. The score reduction remained significant for goserelin at the 12 months follow up [6].

Interventional and operative treatment As published by Traber et al. [25], patients with an OVR originating from the left renal vein (diagnosed with CT scan) were assigned to treatment with coiling, if the left ovarian vein was  10 mm. In 98 patients, coiling was performed (Figure 5) and in 47/181 patients with © 2016 Hogrefe

OVR, clipping was performed (Figure 6). Thirty-three patients did not wish to be treated. One patient suffered from left flank pain after the coiling intervention. After laparoscopic clipping, the patients complained about pain in the right shoulder (CO2 insufflation) and intestinal discomfort. The procedures are described in detail in the published paper [25]. The patients were not investigated for clinical symptoms prospectively, so follow-up data are not yet available. Nevertheless, this is the largest population published so far, where clipping and coiling of the left ovarian vein were performed according to a protocol, using the venous diameter to decide on the specific intervention. A case report illustrating the interventional treatment options is published in this issue [34].

Conclusions PCS and LRVS may be associated. Varicose veins in the pudendal and perineal regions as well as the inguino-femoral region should raise the suspicion of PCS. A questionnaire helps to assess a pain pattern. Whether the therapeutic approach can be chosen using the ovarian vein diameter ( 10 mm clipping) has to be investigated by a prospective outcome study.

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