F1000Research F1000Research 2046-1402 F1000 Research Limited London, UK 10.12688/f1000research.10477.1 Clinical Practice Article Articles Vascular Diseases (Non-Coronary) Atypical presentations and treatment variations of pelvic congestion syndrome: A four patient case series

[version 1; peer review: 1 not approved]

 Greuner David 1 Amorosso Andrew https://orcid.org/0000-0001-7630-3903 a 1 Rotgans Arno 1 Hollingsworth Chris 1 Tonis Adam 1 New York City Surgical Associates Surgical Group, New York, New York, 10022, USA aamorosso@nycsurgical.net

DG, AA, AR and CH all served as primary authors on this paper making substantial contributions to the design conception, acquisition, analysis and interpretation of the data for this paper. All four authors were substantially involved in the intellectual content drafting and subsequent revisions of this paper. All four authors gave approval for final version of this paper for publication and agree to be accountable for all aspects of the work therein. All authors ensure any questions related to the accuracy or integrity of any part of this work will be appropiately investigated and resolved. AT served as a scientific advisor for the entire duration of the data gathering phase of this research. AT also contributed through critically evaluating all drafts of this paper in the editing process.

Competing interests: No competing interests were disclosed.

 22 12 2016 2016 5 2906 19 12 2016 Copyright: © 2016 Greuner D et al. 2016 This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This is a retrospective case review of four patients randomly selected from a pool of 43 patients who presented to our practice with historically atypical symptoms for pelvic congestion syndrome, and the treatment they received. These 43 patients were treated between June and December of 2016. Each patient presented with various atypical symptoms including chronic lower back pain, urinary frequency and incontinence, hip pain, tenesmus, and uncontrollable flatulence. Diagnostic abdominal and pelvic duplex ultrasound and fluoroscopic venography was performed on all patients with informed consent. The four selected patients for this study were all positive for pelvic venous reflux, pelvic venous insufficiency and ovarian/gonadal vein reflux and varicosities. All four of the patients selected in this retrospective study were examined at 1 week from date of intervention and again at 1 month from date of intervention. At the 1 week postoperative exam all four patients had experienced significant resolution of their symptoms, although all had residual congestion present on their right side. After re-intervention to treat right sided congestion via the right gonadal vein, at the 1 month postoperative exam all four patients had experienced an almost complete resolution of symptoms.

 Pelvic Congestion Syndrome venous reflux pelvic reflux chronic venous insufficiency PCS The author(s) declared that no grants were involved in supporting this work. Introduction

Pelvic congestion syndrome (PCS) presents as a constellation of symptoms all caused by the development of varicosities in veins typically drained by either the ovarian or internal iliac veins. Its typical presentation is one of noncyclical dull, aching pelvic pain, typically unilateral, and persisting for more than 6 months. It was present in all patients in our series. Other symptoms that are commonly associated with the condition include dysmenorrhea and dyspareunia, seen respectively in case 1 and 4, and to some degree in all patients in our series.

Our experience has shown us that many authentic pelvic congestion syndrome diagnoses are being lost in a newfound reliance on cross sectional imaging as a diagnostic measure. We have found that to truly diagnose active pelvic congestion syndrome and treat the patient’s correlating symptomatic disease, the gold standard diagnostic imaging modality is fluoroscopic venography. In the following four cases you will read about patients who presented at our practice with historically atypical symptoms for pelvic congestion. After our suspicions were confirmed with duplex sonography revealing ovarian vein reflux and/or pelvic varicosities each patient underwent a fluoroscopic venogram and the appropriate image guided treatment. Although all of these patients presented with symptoms that are not indicative of pelvic congestion, all patients did indeed have advanced pelvic congestion. When each patient was treated for their specific disease state in the pelvic congestion syndrome treatment spectrum all symptoms resolved. Our intention is that the documentation of this experience will help other clinicians in their vigilance to rule out pelvic congestion syndrome with fluoroscopic venography before starting patients on a long road to a differential diagnosis.

Case 1: Hip pain

A 61-year-old female with two children presented to our clinic with a chief complaint of left hip pain for 5 years, as well as pain in her lower back and pelvis, dysmenorrhea, and urinary frequency present for 2 years. Her hip pain was dull and aching in quality, though severe enough to interfere with exercise. She denied paresthesia radiating from her back down into either thigh, and she denied any history of prior trauma to the area. The patient had been seen both by orthopedists and pain management specialists, and both an MRI and a bone scan failed to pinpoint an etiology. She had taken non-steroidal anti-inflammatory drug (NSAID) regimens, systemic corticosteroids, and ultrasound-guided steroid injections without any improvement in her pain.

The patient’s past medical history was also notable for chronic venous insufficiency refractory to conservative and operative management, with endovenous thermal ablation therapy for the great saphenous veins in both legs. Three months after operative treatment, the patient reported continued pain, heaviness, fatigue, throbbing, cramping, and edema in both legs, aggravated by prolonged standing, and consistent with persistent chronic venous insufficiency.

On physical examination, the lower extremities were remarkable for spider veins, reticular veins, varicose veins, and mild pigmentation in her ankles and calves. Infragluteal varices were present. There was some mild pitting edema present, around the ankle and calf bilaterally.

A duplex sonogram was performed on both the pelvis and lower extremities. On sonographic examination of her pelvis, reflux was noted in her pelvic veins. In the legs, persistent reflux was noted in superficial veins in both legs.

A fluoroscopic venogram was performed on the patient, with access obtained at the right common femoral vein. The study noted significant reflux in both internal iliac veins and reflux and stenosis in the left common iliac vein. Delayed washout of contrast was seen in the cross-pelvic collaterals of the tributaries off the internal iliac veins. Most notably, significant varicosities with delayed contrast washout were seen extending off the left ovarian vein ( Figure 1) and communicating with the internal iliac veins. The varicose circulation form the refluxing left gonadal vein included prominent lateral extension towards the left side of the patient. Embolization of the left ovarian vein and collaterals from both internal iliac veins was performed. Post-embolization venography performed immediately after demonstrated successful closure of these refluxing venous branches.

Pre-embolization fluoroscopic venogram showing reflux in ovarian vein.

The patient’s post-procedure course was uneventful. When seen again in our clinic 8 days later, her symptoms were significantly improved. Her hip pain had almost completely resolved, and at her 4 week post-operative checkup the patient reports she is again able to exercise without any impediment.

 Case 2: Back pain

A 34-year-old female with 3 children by Cesarean section presented with an 8 year history of back pain. The pain was described as a dull ache, which increased throughout the day and improved after long periods in a recumbent position. She denied any radiation of her pain down her thighs. She denied any history of trauma. She did however, note some increase in the severity of her pain with increases in temperature and around the time of her menses. She had been on NSAIDs and had multiple spinal manipulations with a chiropractor with no improvement in her symptoms. An MRI of the lumbar spine showed only a mild L4 disc protrusion, and a nerve conduction study (NCS) showed no evidence of lumbosacral radiculopathy.

Upon further questioning, the patient noted a dull ache on the left side of her pelvis, and pain, cramping, and edema in both legs. As with her back pain, these symptoms would worsen with both daily activity and prolonged standing or sitting, and were worse on the left side. Her leg symptoms would improve slightly with leg elevation.

On physical examination, the lower extremities were remarkable for varicose veins and mild pitting edema noted around the ankle and calf bilaterally.

A duplex ultrasound examination was performed on the pelvis. A dilated left ovarian vein was visualized with 4.2 seconds of reflux.

An initial fluoroscopic venogram was performed that demonstrated severe reflux in her internal iliac veins bilaterally, with cross-pelvic collateral circulation lying near the sacrum, and also showed significant dilatation and reflux in both a left primary and accessory ovarian vein, both terminating into large and dilated pelvic varicosities that communicated with the left internal iliac vein and the right internal iliac vein via cross-pelvic collaterals. An intravascular ultrasound (IVUS) catheter noted dilation of the right ovarian vein as well. Embolization of both left ovarian veins was performed using a polidocanol and gelfoam slurry. The patient was brought back to the radiology suite 2 weeks later for a repeat venogram. During this procedure, the pelvic varicosities extending off branches of the left internal iliac vein approaching the sacrum, were embolized with gelfoam slurry and detachable coils. Closure of the left ovarian vein from the prior procedure was confirmed with a left renal venogram, and a post-embolization venogram confirmed closure of the internal iliac varicosities.

Roughly seven weeks after her two embolizations, the patient reported vast improvement in her symptoms on the left, both in her pelvis and in her back. She did, however, have persisting symptoms on her right side, and in addition noted post-coital tenderness that she was now noticing as some of her other discomfort was resolving. A follow-up sonogram demonstrated resolution of the left ovarian vein reflux, but significant reflux and varicosities on the right side of her pelvis consistent with right-sided pelvic congestion. At the 10 week mark from her initial treatment she has returned to the procedure suite for a third venogram with embolization of the right gonadal vein ( Figure 2) and at the 12 week post-operative point has full resolution of her symptoms.

Fluoroscopic venography of ovarian vein showing reflux and varices. Case 3: Tenesmus and uncontrollable flatulence

A 42-year-old multiparous woman presented to our clinic with 8 years tenesmus, fecal incontinence, and uncontrollable flatulence. These symptoms began shortly after the birth of her first child. The pregnancy was notable for a significant amount of pain and swelling in her legs and pelvis, and the vaginal delivery was assisted with an episiotomy. Although she had some improvement in her symptoms in the months after her pregnancy, she has since had 4 more pregnancies. Despite having Cesarean sections for her deliveries, each pregnancy has worsened her incontinence and overall bowel control, as well as her baseline control. She has been evaluated by gastroenterologists for the above problems, as well as for gas and bloating in her abdomen. She has undergone endoscopies and multiple imaging studies, and was diagnosed with Irritable Bowel Syndrome. Lastly, the patient had a history of hemorrhoids, which had bled on at least one occasion.

In addition to her bowel symptoms, the patient reported problems with urinary frequency, dyspareunia, and pelvic heaviness, and ovarian pain. Her pain would worsen around the time of her menses. She has been followed by a gynecologist for these issues, which were attributed to endometriosis. Her obstetrician has also attributed her incontinence issues to the episiotomy and postpartum pelvic floor dysfunction, and had suggested a potential sacral nerve stimulator implant to help her.

The patient also noted some cramping, heaviness, and swelling in both legs. These symptoms would worsen with daily activity, as well as with prolonged standing or sitting. She has had hemorrhoids and varicose veins over her perineum, and has had intermittent bleeding from both.

For all these symptoms, and despite her extensive workup by both gastroenterologists and gynecologists, the patient had been unable to find any relief for her numerous problems.

On physical examination, the lower extremities were remarkable for spider veins, varicose veins, prominent perineal veins, and vulvar varicosities. Mild pitting edema was noted as well. The abdomen was soft, with some ovarian tenderness on palpation. Duplex examination of the pelvis was performed. A collection of pelvic varicosities was seen surrounding the rectum.

A diagnostic fluoroscopic venogram was performed using a right common femoral vein approach. Moderate reflux was noted in the common iliac veins and significant reflux noted in the internal iliac veins, with delayed contrast washout noted in several varices and cross-pelvic collaterals. The exam, however, was most notable for an immensely dilated left ovarian and accessory left ovarian vein. They were roughly 28–30 mm in diameter, showing delayed contrast washout and collateralization with the internal iliac veins. A large and aneurysmal terminal branch of the vessels was noted to lie on the sigmoid colon. The left ovarian vein, its accessory, and its branches were embolized with a combination of gelfoam slurry and a 20mm detachable coil. Embolization of the internal iliac branches bilaterally was performed with gelfoam. Post-embolization venography performed immediately after embolization, demonstrated successful closure of all concerning branches.

At 1 week out from her embolization, the patient has had almost complete resolution of both her flatulence and her tenesmus. At the 4 week post-operative mark she had improvement with her bladder control and dyspareunia as well. She has some residual pelvic pain, and will be returning for another diagnostic venogram with an intravascular ultrasound (IVUS) to assess the reflux in her common iliac veins.

 Case 4: Back pain

A 36-year-old multiparous woman presented to our clinic for pain, cramping, and edema in both legs for roughly 5 years. Of note, she was having significant back pain as well, which she chose to disclose after experiencing relief following venogram with successful embolization of the left gonadal vein and collaterals from the refluxing internal iliac veins.

In regard to her presenting complaint, her symptoms worsened over the course of the day and improved with leg elevation. They had shown no improvement with compression therapy and daily NSAIDs. Duplex sonography showed superficial venous reflux, which was ablated. Postoperative sonograms showed successful closure of each vein.

Four months later, the patient experienced a relapse of her leg pain and cramping. A repeat sonogram was performed, which showed reopening of all previously ablated veins. A sonogram was performed on the pelvis, which showed 2.9 seconds of reflux in the left ovarian vein. On further questioning and examination, the patient was found to have pelvic pain and varicosities in her inguinal area, extending to the vulva, most prominently on the left. These varicosities had been a cause of dyspareunia for the patient for several years, beginning shortly after the birth of her third child.

A diagnostic fluoroscopic venogram was performed from a right common femoral vein approach. Severe reflux was seen in the left internal iliac system, with cross-pelvic flow to the right side as well as retrograde contrast filling of the left ovarian vein. The left ovarian vein was almost as large as an iliac vein- roughly 14 to 16 mm in diameter. The left vein was embolized with a combination of polidocanol and gelfoam slurry. A post-procedure venogram was performed immediately after embolization and showed only moderate closure of the vein however, and intervention in the internal iliac system was thwarted due to vasospasm.

A repeat venogram was performed 10 days later, again with a right common femoral vein approach. Reflux was still seen in the branches off both internal iliac veins. The left ovarian vein remained open and dilated, with delayed contrast washout. Embolization was again performed, this time on the left ovarian vein and on the collaterals extending from both internal iliac veins, using a combination of gelfoam slurry and a 13 mm detachable coil. Post-embolization venography immediately after coil placement showed successful closure of the refluxing veins. Visualization of the right iliac veins was performed using an IVUS catheter and showed no evidence of stenosis.

At 8 weeks out from our first intervention, the patient has had significant reduction in her pelvic pain. She also mentions finding reduction in back pain which she reported upon experiencing relief status-post venogram interventions with embolization.

 Discussion

Pelvic congestion syndrome (PCS) presents as a constellation of symptoms all caused by the development of varicosities in veins typically drained by either the ovarian or internal iliac veins. Its typical presentation is one of noncyclical dull, aching pelvic pain, typically unilateral, and persisting for more than 6 months. It was present in all patients in our series. Other symptoms that are commonly associated with the condition include dysmenorrhea and dyspareunia, seen respectively in case 1 and 4, and to some degree in all patients in our series.

PCS is also seen in association with lower extremity varicose veins. As many as 15–20% of patients with lower limb varicosities have demonstrated pelvic venous reflux on venogram or duplex ultrasound, with a 30% incidence among those patients with varicosities that have recurred after prior treatment 1 . On physical examination, these patients may often have varicosities on the vulva, on or just beneath the buttocks, and on the upper thighs, particularly near the groin, owing to reflux from the pelvic veins communicating to the legs via the inferior gluteal and internal/external pudental veins 2 . In our series, cases 1 and 4 had reopening of veins previously closed by endovenous thermal ablations. Cases 1, 3, and 4 presented with either vulvar or infragluteal varices.

It is important to remember that PCS affects its patients due to the local compression and consequent irritation and inflammation of organs in proximity to the engorged and swollen plexus of pelvic veins. Since these veins drain the bladder, vagina, uterus, rectum, and sacrum, PCS can be responsible for several atypical symptoms, depending on the organ compromised. Some form of bladder instability is not uncommon, and was seen in cases 1 and 3. Irritation of the lumbosacral nerves, although uncommon, can result in either back or hip pain. In our series, back pain was seen in cases 1 and 2. Hip pain was seen in case 1. The finding of hip pain is particularly rare, with only 2 other cases being reported in the literature 3 . Pressure of these veins on the rectum, or perhaps reflux through collaterals feeding off a refluxing ovarian vein, can result in hemorrhoids, a finding seen in case 3. The finding of a dilated pelvic varicosity compressing the sigmoid colon and causing both tenesmus and uncontrollable flatulence in case 3 has never before been reported.

As shown in our first three cases, this atypical presentation of PCS can be the predominant issue impacting the patient’s quality of life. These atypical presentations are typically underdiagnosed, as seen by the extensive and ultimately unfruitful workups experienced by 3 of the 4 patients in our series. It is therefore important to maintain a low threshold for suspicion of PCS in any patient with symptoms that can be attributed to an organ in the pelvis.

Our workup for suspected PCS begins with pelvic sonography. Although there has been literature championing the efficacy of either the CT venography (CTV) or more often the magnetic resonance venography (MRV), in our experience, both studies have had a lower diagnostic yield 4– 6 . Both imaging modalities require proper timing to catch the contrast in the pelvis during the venous phase, and are therefore very operator dependent. The studies also require the subject to be supine, a position that can compress ordinarily dilated pelvic veins. They are also expensive. In contrast, pelvic sonography is inexpensive, and can be performed with the patient upright, as the examiner looks for both dilated pelvic veins and flow reversal during Valsalva maneuvers 7 . The operator-dependent nature inherent to sonography mandates valuable sonogram technicians with high levels of training and experience in finding and reporting pelvic reflux and varicosities.

As with the CTV and MRV, the sonogram is also capable of ruling out other pelvic etiologies. Findings suggestive of PCS on ultrasound include ovarian veins >6 mm in diameter, the presence of dilated (>5 mm) arcuate veins crossing the uterine myometrium, and slow (<3 sm/sec) or reversed retrograde blood flow 2, 6 . Polycystic changes in the ovaries have also been seen in about 50% 4, 6 of cases.

Diagnostic venograms remain the gold standard in identifying PCS, and are indicated for all suspicious presentations, even, in the appropriate clinical setting, if the other studies are negative. It is a low risk procedure, and permits treatment and potential curing of the patient’s symptoms at the same time. Evaluation of the left renal, bilateral ovarian, iliac, and internal iliac veins is performed, looking for dilatation and reflux. Venography findings include an ovarian vein diameter >5 mm, ovarian vein reflux, stagnation of contrast in the pelvic veins, contralateral reflux across the midline, and filling of vulvoperineal or thigh varices 2, 4 . If there is a question of a stenotic lesion in either the renal or iliac vein, pressures across the area in question can be measured, or an intravascular ultrasound can be placed. In all of our patients, pelvic venograms successfully identified the condition.

In our clinic, we perform diagnostic venography with the patient awake. We begin our assessment at the most common site of pelvic reflux, the left ovarian vein. If reflux is present, we attempt to reproduce the patient’s symptoms using high pressure contrast flushes in a 5 french sheath. If the venous distension created by the flush reproduces symptoms, and the anatomic distribution of the vessels distended corresponds to those symptoms, we embolize the vessel. Our preference in the ovarian vein is to use a combination of gelfoam or polidocanol for the terminal branches below the pelvic brim and an oversized (at least 150% of the diameter of the ovarian vein) coil in the ovarian vein, preferably near the ostia of any visualized ovarian collaterals, and no less than 4 mm from its confluence with the renal vein.

After the treatment, we revisit the patient in roughly 1 week. If the patient is showing improvement, we repeat the pelvic sonogram to determine if any reflux remains. If reflux is noted, we perform a second venogram and embolization of pelvic varices fed by the refluxing internal iliac veins, and potentially the right ovarian vein if the patient’s symptoms are significantly greater on the right. Our preference is to treat the internal iliac branches with either sclerotherapy or gelfoam alone, given the higher risk of coil migration noted in this region. If the right ovarian vein is to be targeted, we consider a right internal jugular access to allow for easier cannulation.

During this second procedure, we also employ an IVUS catheter to look for stenotic lesions. Pelvic reflux can frequently be secondary to anatomic anomalies resulting in downstream obstruction, such as compression of the left renal vein by the superior mesenteric artery (Nutcracker syndrome) 1, 2, 7 , or compression of a left common iliac vein by a right common iliac artery (May-Thurner syndrome) 8 . A May-Thurner’s phenomenon can be present in as many as two-thirds of the general population 9 . If any such lesions are identified, a full discussion with the patient regarding the anatomy affected by the stenosis, and the benefits and drawbacks of angioplasty alone versus stenting ensues.

If the patient wishes to proceed, we return for a third venogram to treat the stenotic segments. For milder lesions (≤ 50% reduction in cross-sectional area), or for focal, short lesions caused by a localized vascular band or web, we attempt only an angioplasty. For a longer and more severe stenotic segment (> 50%), we prefer to both angioplasty and stent. As with our coils, our preference is to oversize our stents (roughly 4 mm greater than the average diameter of the non-stenotic venous segment). Our preference is to avoid stenting for as long as possible in women who intend to get pregnant and in patients with clotting disorders or prior DVTs, given the higher incidence of post-stent complications in these patient populations.

Transcatheter embolization is currently regarded as the least invasive and most efficacious management option for PCS, with complete or partial symptom relief in 68.2–100% of patients 2, 10 . Apart from our preferences, a number of different approaches have been reported to affect closure of the refluxing veins, from simple coil embolization, to glue embolization, to combinations of sclerotherapy and coils. In studies using visual analog scale (VAS) pain scores to measure the extent of symptom relief, vast improvement was shown consistently, with mean scores of 7.3–7.6 decreasing to scores of 0.5–3.2 postoperatively. Depending on the initial severity, the symptoms can take as long as 9–13 months after therapy to resolve 10 . Complications from the procedure are rare, being reported in 3.4–4.4% of patients, and consist of coil migration, vein perforation, local phlebitis, deep venous thrombosis, and contrast reactions 10 . Patients may suffer from a brief period of flu-like symptoms within 72 hours of each embolization, but this consistently passes within 48 hours without need for intervention. Studies have also shown embolization to have no effect on the menstrual cycle or fertility 4 . This is an important consideration, given that the predominance of PCS is in premenopausal women.

With respect to the management of PCS secondary to stenotic vein lesions, endovenous stent placement is also safe and effective. In a review of multiple studies encompassing 1500 patients being treated for chronic iliac vein stenosis, stenting had a 90–100% patency rate for non-thrombotic disease and 74–89% patency rate for thrombotic disease at 3 to 5 years. Symptom relief was achieved in 86–94% of patients for pain, 66–89% for swelling, and 58–89% for healing of ulcers in the leg 11 . Although these studies focused on the outcomes of patients suffering from venous insufficiency in the legs, it is not unreasonable to assume that treatment of the stenosis would similarly benefit patients with PCS, given that both ailments are due to venous obstruction causing congestion in communicating upstream veins. Among the 1500 patients reviewed, no deaths or pulmonary emboli were reported, and access site complications and significant bleeding, despite the larger sheaths required for the stents, occurred in only 0.03–1% 11 .

Given the effectiveness and safety of these procedures, our practice recommends aggressive management of patients whose symptoms and venogram findings suggest the presence of PCS.

 Conclusion

Pelvic congestion syndrome is an underdiagnosed condition in premenopausal women that presents with a broad spectrum of symptoms that are often attributed to other pathologies. It is important to maintain a high level of suspicion in parous women wether the presenting symptoms are typical or atypical in nature. The complexity of the abdominal/pelvic venous vasculature in the premenopausal patient can distort accuracy and cloud the patients ability to properly articlutale symptoms. With modern advancements made in diagnostic imaging many clinicians feel MRV to be definitive in diagnosing pelvic congestion, but our experience has proven otherwise. Cross sectional imaging relies heavily on timing, patient immobility and technical skill level of the performing technologist and even then can still provide false positive reults 2, 4, 6 . Our experience has shown us that fluoroscopic venography is the gold standard diagnostic imaging modality providing us with anatomical correlation as well as physiological confirmation of our suspicions. In this specific patient population a diagnostic venogram will go far in preventing patients with PCS from missing out on effective and low risk treatment.

 Consent

Written informed consent for publication of their clinical details was obtained from each patient in this paper.

 Lopez AJ : Female Pelvic Vein Embolization: Indications, Techniques, and Outcomes. Cardiovasc Intervent Radiol. 2015;38(4):806–820. 25804635 10.1007/s00270-015-1074-7 4500858 Durham JD Machan L : Pelvic congestion syndrome. Semin Intervent Radiol. 2013;30(4):372–380. 24436564 10.1055/s-0033-1359731 3835435 Shelkey J Huang C Karpa K : Case report: pelvic congestion syndrome as an unusual etiology for chronic hip pain in 2 active, middle-age women. Sports Health. 2014;6(2):145–148. 24587865 3931334 Bittles MA Hoffer EK : Gonadal vein embolization: treatment of varicocele and pelvic congestion syndrome. Semin Intervent Radiol. 2008;25(3):261–270. 21326516 10.1055/s-0028-1085927 3036435 Greiner M Dadon M Lemasle P : How does the patho-physiology influence the treatment of pelvic congestion syndrome and is the result long-lasting? Phlebology. 2012;27(Suppl 1):58–64. 22312069 10.1258/phleb.2011.012S07 Ignacio EA Dua R Sarin S : Pelvic congestion syndrome: diagnosis and treatment. Semin Intervent Radiol. 2008;25(4):361–368. 21326577 10.1055/s-0028-1102998 3036528 Liddle AD Davies AH : Pelvic congestion syndrome: chronic pelvic pain caused by ovarian and internal iliac varices. Phlebology. 2007;22(3):100–104. 18268860 10.1258/026835507780807248 Marsh P Holdstock J Harrison C : Pelvic vein reflux in female patients with varicose veins: comparison of incidence between a specialist private vein clinic and the vascular department of a National Health Service District General Hospital. Phlebology. 2009;24(3):108–113. 19470861 10.1258/phleb.2008.008041 Raju S Darcey R Neglén P : Unexpected major role for venous stenting in deep reflux disease. J Vasc Surg. 2010;51(2):401–408; discussion 408. 20006920 10.1016/j.jvs.2009.08.032 Meissner MH Gibson K : Clinical outcome after treatment of pelvic congestion syndrome: sense and nonsense. Phlebology. 2015;30(1 Suppl):73–80. 25729071 Raju S : Best management options for chronic iliac vein stenosis and occlusion. J Vasc Surg. 2013;57(4):1163–1169. 23433816 10.1016/j.jvs.2012.11.084 10.5256/f1000research.11290.r19932 Reviewer response for version 1 Whiteley Mark S 1 2 Referee https://orcid.org/0000-0001-6727-6245 Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK The Whiteley Clinic, Guilford, UK

Competing interests: No competing interests were disclosed.

 20 2 2017 Copyright: © 2017 Whiteley MS 2017 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation reject

I was very interested to read this article as the investigation and treatment of pelvic congestion syndrome (PCS) and pelvic venous reflux (PVR) is very topical at the moment and is a major area of interest for me. As clinicians seeing these patients, we need good quality research to develop our understanding of this complex collection of signs and symptoms, which may have underlying causes of both venous reflux and/or venous obstruction. I congratulate the authors on their attempt to define their rationale for their approach to this complex condition. However I do have some concerns about version 1 of this paper as it appears at present.

I will detail these concerns below but before getting into the detail, there are two main points that need to be addressed. The first is why only 4 cases were presented when the authors state that they have seen 43 such atypical presentations. The second is why the paper concludes that fluoroscopic venography is a gold standard investigation for PCS when this is essentially a case series concentrating on atypical presentations of PCS and is not a study comparing fluoroscopic venography with any other method of diagnosis. As discussed in the review of the cases that they have presented, an alternative strategy might have been more beneficial to patients and reduced the need for invasive venography.

To address the points in order as they appear within the version 1 paper.

Abstract:

The first and most obvious question as outlined above, why would the authors choose 4 cases “at random” from 43 who presented with atypical symptoms for PCS? As we are at the stage of trying to understand PCS, and the symptoms that PCS may cause 1  the authors are missing a valuable opportunity to write up a case series of 43 atypical cases. To write up all 43 and to show trends and common features in these would represent at large series of typical presentations of PCS and would be a very useful contribution to the literature. I cannot understand the rationale to present only 4 at random of 43 cases as such a small sample of the cases (<10% of the total) could potentially miss some vital associations in such cases. 

The authors do not make it clear where the venous reflux/insufficiency was found. They state: “ The four selected patients for this study were all positive for pelvic venous reflux, pelvic venous insufficiency and ovarian/gonadal vein reflux and varicosities.” However I am unclear as to what they mean by this as some of the terms overlap. As written it appears to say that these patients have ovarian/gonadal vein reflux and varicosities, but also says they have “pelvic venous insufficiency” and also “pelvic venous reflux.” These terms are generally used to mean the same thing and, if the authors aren’t using these terms in this way, do they mean other pelvic veins? This needs to be made clearer.

The conclusion of the abstract does not fit with the conclusion of the paper. This is addressed in the conclusion section.

Introduction:

The authors give their opinion as to the validity of fluoroscopic venography without supporting evidence. They state “ We have found that to truly diagnose active pelvic congestion syndrome and treat the patient’s correlating symptomatic disease, the gold standard diagnostic imaging modality is fluoroscopic venography.” The authors should reference where they have published this finding from studying it appropriately or, if they have not done such a study, they should reference the study they use that does justify this claim. As PCS is difficult to diagnose, for the authors to state that they can “truly diagnose” the condition with venography, there needs to be very good evidence supporting this. If evidence cannot be produced, it should be made clear that this is the authors opinion and even that it may be a widely held opinion, especially in the light of our work with transvaginal duplex ultrasound scanning (TVS) 2 . 

Our own work suggests that transvaginal duplex ultrasound (TVS) performed with our specific protocol is the gold-standard way of assessing pelvic venous reflux.

The authors do not state whether their duplex ultrasound examination was external (transabdominal) or transvaginal: “ After our suspicions were confirmed with duplex sonography revealing ovarian vein reflux and/or pelvic varicosities … ” In the discussion, they do say it can be performed standing and during Valsalva, but as they don’t comment on the imaging of internal iliac veins and their territories, it appears that it is an external trans-abdominal scan.

Trans-abdominal duplex ultrasound is not able to see reflux in distal ovarian veins, internal iliac vein tributaries, nor deep varicosities in most normal patients – hence the superiority of TVS over trans-abdominal scanning. As our published research shows that most pelvic vein reflux is in the internal iliac vein tributaries 2 , 3  the authors should note that if their criteria for proceeding to venography is as stated: “ suspicions were confirmed with duplex sonography revealing ovarian vein reflux and/or pelvic varicosities …” then they are potentially missing some cases too – something they have criticised others for doing by relying on cross-sectional imaging.

The authors state that all 4 patients: “ did indeed have advanced pelvic congestion”. How was this confirmed to be “advanced”. Do they mean there was massive reflux in the relevant pelvic vein? Or that more than one pelvic vein was involved? Or that there were large varicosities? As there is no proven classification for PCS yet, the authors would be better to describe what the hemodynamic abnormalities were, rather than claim that these were “ advanced pelvic congestion”.

The authors cannot make the claim that they do in their statement: “When each patient was treated for their specific disease state in the pelvic congestion syndrome treatment spectrum all symptoms resolved” as in 2 of the 4 cases they present, there were residual symptoms noted at the end of the reported follow-up. (Case 3 and case 4).

In view of the shortcomings noted above and also some more to come below, the authors stated aim of: “Our intention is that the documentation of this experience will help other clinicians in their vigilance to rule out pelvic congestion syndrome with fluoroscopic venography before starting patients on a long road to a differential diagnosis” might not be the optimal advice to give to other clinicians.

Despite the current conclusion in version 1 of the paper and the authors stated view that fluoroscopic venography is the gold standard for PCS, the cases as presented does not support this protocol when compared to a protocol starting with diagnostic TVS.

Case 1:

This patient had reflux in left ovarian and bilateral internal iliac veins which is the commonest pattern of reflux 2 , 3 . This diagnosis can be made with one TVS without the need for trans-abdominal duplex followed by invasive diagnostic venography. Even if the case should be made that the diagnostic venogram is also a therapeutic intervention, the protocol and patient pathway as outlined in this report results in neither the doctor nor patient knowing the extent of the intervention (i.e. how many vein needing coil embolization) before the procedure. Also, as the authors have noted that they use the femoral approach for their initial venogram, but a right jugular approach if they subsequently find the right ovarian vein requires treatment, a TVS would give them the information that they need to plan the therapeutic approach, something that their current protocol does not allow for.

Case 2:

This patient had all 4 territories involved - bilateral ovarian vein (with accessory vein on the left) and bilateral internal iliac vein reflux. The patient had transabdominal duplex (as in the introduction to suggest PCS) 2 venograms to attempt to treat the left ovarian and bilateral internal iliac veins reflux, IVUS to diagnose the right ovarian vein reflux – leading to a third venogram and embolization. If TVS had been used to diagnose the reflux, all 4 veins would have been found to be refluxing on the first diagnostic test and all 4 would have been targeted in the therapeutic venogram for embolization.

Case 3:

Again, this patient had the most common pattern we have reported of left ovarian vein and bilateral internal iliac veins refluxing 2 , 3 albeit with an accessory left ovarian vein in this case. This patient was somewhat successfully treated with one diagnostic/therapuetic venogram and so there would not be a clear advantage to state a TVS would have changed the course of this treatment. However, it needs to be noted that the symptoms are not fully resolved and the patient is due an IVUS to investigate this residual pain.

Case 4:

Once again the commonest pattern of left ovarian and bilateral internal iliac vein reflux 2 , 3 where the patient ended up having with 2 venograms and a negative IVUS. They would probably have had only one therapeutic venogram with embolization if diagnosis by TVS had been the primary diagnostic text.

Discussion:

The authors state that the symptoms of PCS were found in all patients in their series. Do they mean the 4 presented or all of 43 that had atypical symptoms? This is the sort of data that reporting all 43 would have elucidated.

The authors quote the incidence figures from a review article by Lopez 4  rather than going to the source data that Lopez quotes. By doing so, they have repeated the inaccuracies that Lopez made in his article. They state: “As many as 15–20% of patients with lower limb varicosities have demonstrated pelvic venous reflux on venogram or duplex ultrasound, with a 30% incidence among those patients with varicosities that have recurred after prior treatment”.

However, the sources that Lopez quotes don’t actually give those figures. The first figure given for “patient with lower limb varicosities” was from Marsh’s paper in 2009 3  which only included females and actually gave the figures of approximately 20% of patients having non-saphenous lower leg venous reflux arising from the pelvis and approximately 16% having truncal pelvic vein reflux. Indeed, in men, our recent presentation at the American Venous Forum has shown it is only 3% 5 , and so when copying the figures from Lopez, the wrong impression to prevalence is given as there is no mention of sex.

With respect to the quoted “30% incidence among those patients with varicosities that have recurred after prior treatment”, once again this is taken from Lopez where he has not appreciated the data in the source paper 6 . In fact the 30% incidence is related to legs with recurrent varicose veins rather than patients, and this rate was only found in females who have had children. When a smaller number of men were added (group 1 in the study F:M 97:12) this dropped to 25% showing that this is predominantly a female problem, but not exclusively 5 .

The authors state as fact what most of us believe that “It is important to remember that PCS affects its patients due to the local compression and consequent irritation and inflammation of organs in proximity to the engorged and swollen plexus of pelvic veins.” However to quote this as a fact requires a reference showing that inflammation has been measured in the veins or surrounding tissues, related to the venous dilation. This becomes very important when considering PCS from obstructive causes rather than reflux, as well as when considering other possible treatment strategies such as anti-inflammatory medication.

The authors state that “Findings suggestive of PCS on ultrasound include ovarian veins >6 mm in diameter” and later in the same section “Venography findings include an ovarian vein diameter >5 mm.”  However ovarian vein diameter has been shown to be irrelevant in ovarian vein reflux 7 . Therefore the authors should state that this was their protocol and should note that there is now some doubt as to the validity of this measurement.

Once again the authors state that “ Diagnostic venograms remain the gold standard in identifying PCS,” which requires evidence or references to good evidence. Unless there is clear proof, then this should be changed to a more accurate statement such as “Diagnostic venograms are believed by many to be the gold standard in identifying PCS,” and the authors should quote the TVS work to inform readers that this might not be the case anymore 2 .

The authors also claim that “In all of our patients, pelvic venograms successfully identified the condition.” This is not correct according to their own text. Case 2 required IVUS to diagnose the right ovarian pathology.

The authors have written “ … or compression of a left common iliac vein by a right common iliac artery (May-Thurner syndrome) 8.” This reference is not correct. Reference 8 corresponds to the Marsh paper which looks at prevalence of non-saphenous leg vein reflux and the association with pelvic venous reflux – not May-Thurner syndrome.

I am concerned by the statement that “Given the effectiveness and safety of these procedures, our practice recommends aggressive management of patients whose symptoms and venogram findings suggest the presence of PCS.” in that the authors had been including stents as well as coils in the preceding text. In view of some reports now being presented at academic meetings relating to long-term complications of venous stents, principally occlusion by intimal hyperplasia/fibrous tissue and the subsequent need for removal, reconstruction or bypass, the authors may wish to consider this statement carefully. There is good reason to add a cautionary note to this paragraph, particularly as these patients tend to be younger, being pre-menopausal women (as noted by the authors earlier in the discussion).

Conclusion:

Version 1 concludes: “Our experience has shown us that fluoroscopic venography is the gold standard diagnostic imaging modality providing us with anatomical correlation as well as physiological confirmation of our suspicions. In this specific patient population, a diagnostic venogram will go far in preventing patients with PCS from missing out on effective and low-risk treatment.”

The conclusion, as stated currently, does not arise from the information given within this paper. The paper is a case series of four patients, according to the authors chosen at random from 43 possible cases. They have not shown that fluoroscopic venography is a gold standard within this paper. Indeed patients have had to have more than one venography and, in one of the four cases, required IVUS to complete the diagnosis. As was shown multiple times at the end of the last century when colour flow duplex of the leg veins was being compared with venography, refluxing on venography is not necessarily physiological. This is due to the contrast having different physical characteristics than blood and also being injected under pressure hence possibly changing normal flow patterns. Duplex ultrasound, by its very nature, allows observation of flow by reflection of ultrasound from the blood cells, allowing true physiological flow to be seen in real time.

It is also perplexing that the final sentence of the abstract, usually regarded as the conclusion statement in the scientific method, concentrates on the resolution of the atypical symptoms after treatment whilst the conclusion of the actual body of the paper tries to persuade the reader that fluoroscopic venography is a gold standard.

In reality, the only conclusion that can be gleaned from this very small subset (less than 10%) of the atypical presentations that this group have stated that they have seen, is that the atypical symptoms do appear to be related to PCS as correction of reflux identified on transabdominal ultrasound and then fluoroscopic venography, and in one case IVUS, largely resolved. There is no evidence given to support the claims regarding fluoroscopic venography being a gold standard.

Reviewer Expertise:

NA

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

References : Pelvic congestion syndrome masquerading as osteoarthritis of the hip. SAGE Open Med Case Rep .2016;4: 10.1177/2050313X16683630 2050313X16683630 27994874 10.1177/2050313X16683630 : Transvaginal duplex ultrasonography appears to be the gold standard investigation for the haemodynamic evaluation of pelvic venous reflux in the ovarian and internal iliac veins in women. Phlebology .2015;30(10) : 10.1177/0268355514554638 706-13 25324278 10.1177/0268355514554638 : Pelvic vein reflux in female patients with varicose veins: comparison of incidence between a specialist private vein clinic and the vascular department of a National Health Service District General Hospital. Phlebology .2009;24(3) : 10.1258/phleb.2008.008041 108-13 19470861 10.1258/phleb.2008.008041 : Female Pelvic Vein Embolization: Indications, Techniques, and Outcomes. Cardiovasc Intervent Radiol .2015;38(4) : 10.1007/s00270-015-1074-7 806-20 25804635 10.1007/s00270-015-1074-7 : Male Patterns of Pelvic Venous Reflux can be Investigated with Duplex Ultrasound and Treated with Coil Embolization. Journal of Vascular Surgery: Venous and Lymphatic Disorders .2017;5(1) : 10.1016/j.jvsv.2016.10.066 10.1016/j.jvsv.2016.10.066 : Pelvic venous reflux is a major contributory cause of recurrent varicose veins in more than a quarter of women. J Vasc Surg Venous Lymphat Disord .2014;2(4) : 10.1016/j.jvsv.2014.05.005 411-5 26993547 10.1016/j.jvsv.2014.05.005 : Ovarian Vein Diameter Cannot Be Used as an Indicator of Ovarian Venous Reflux. Eur J Vasc Endovasc Surg .2015;49(1) : 10.1016/j.ejvs.2014.10.013 90-4 25457295 10.1016/j.ejvs.2014.10.013 Amorosso Andrew NYC Surgical Associates, USA

Competing interests: No competing interests were declared.

 31 3 2017

Dr.Whiteley, thank you for taking the time to give such a thorough review of our work. I want to let you know that in addition to the initial response I had sent you, your points where so glaringly clear and relevant that I am currently restructuring and rewriting this paper to be more inclusive of all of our valuable work.

There is no reason why we shouldn't share all of our experience. I can tell you that I wanted to put this paper out in 2016 and that is why I put it out as a 4 patient case series. 

I take your suggestions to heart and hope you find the re-write I send in shortly to be more reflective of the type of work we do at our practice.

Your point on the conclusion is absolutely spot on and I guess all I can say is I got lost and didn't circle back to check the two out at the end. I am focused on that as piece together version 2. We will have that loaded in the next week or so and I will then eagerly await your input as it is very valuable to us and the patients we treat. Thank you so much for your help.

Kind Regards,

Andrew