Objective: Although nutcracker syndrome (NS) is rare, patients presenting ... the rarity of this syndrome, the paucity of data, and the short-term follow-up of the ...
A systematic review on management of nutcracker syndrome Camilo A. Velasquez, MD,a Ayman Saeyeldin, MD,a Mohammad A. Zafar, MD,a Adam J. Brownstein, BA,a and Young Erben, MD,b New Haven, Conn
ABSTRACT Objective: Although nutcracker syndrome (NS) is rare, patients presenting with symptoms or signs and anatomic compression of the left renal vein (LRV) can be considered for intervention. Open, laparoscopic, and endovascular techniques have been developed to decrease the venous outflow obstruction of the LRV. The paucity of data regarding the management of this uncommon disease process poses a challenge for adequate recommendations of the best treatment modality. Herein, we aim to present a systematic review for the management of NS. Methods: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards to systematically search the electronic databases of MEDLINE from October 1982 to July 2017 for articles about the management of NS. Included were studies in English, Spanish, and German in all age groups. Results: The literature search provided 249 references. After abstract and full review screening for inclusion, 17 references were analyzed. Eight (47%) described the open surgical approach. The LRV transposition was the most commonly reported technique, followed by renal autotransplantation. Seven (41.11%) described the endovascular technique of stent implantation, and two (11.7%) described the minimally invasive laparoscopic extravascular stent implantation. Conclusions: NS is a rare entity. Multiple techniques have been developed for the treatment of this condition. However, the rarity of this syndrome, the paucity of data, and the short-term follow-up of the existing evidence are the disadvantages that prevent recommendations for the best treatment strategy. Up to now, open surgical intervention, specifically LRV transposition, has been considered by some experts the mainstay for treatment of NS. The endovascular approach is gaining strength as more evidence has become available. However, the long-term patency and durability of this approach remain to be elucidated. Therefore, careful selection of patients is necessary in recommending this technique. (J Vasc Surg: Venous and Lym Dis 2017;-:1-8.)
Nutcracker syndrome (NS), first described in 1937 by Grant,1 refers to patients presenting with symptoms and signs associated with the anatomic compression of the left renal vein (LRV). Most commonly known is the anterior NS, which refers to the compression of the LRV by the superior mesenteric artery (SMA) and the aorta.2-4 A second variant is the posterior NS, in which the LRV is compressed between the aorta and the vertebral body.2,5 Lesser known pathologic processes and conditions leading to LRV compression include pancreatic neoplasms, paraaortic lymphadenopathy, retroperitoneal tumors, overarching testicular artery, lordosis, reduced retroperitoneal and mesenteric fat, and pregnancy.2 Several investigators have described that an SMA branching angle of 4.2 to 5.0 is considered one of the diagnostic criteria of NS.15 The disadvantages of DUS are the variability with positional changes, the technical difficulties resulting from a small sampling area, and the interobserver variability.2 CTV and MRV can also be obtained, and they can be used to demonstrate compression of the LRV, gonadal
vein distention, and pelvic congestion. Furthermore, findings such as an LRV hilar diameter to aortomesenteric diameter ratio of >4.9, the “beak sign,” and an SMA branching angle of 1 mm Hg.2,16 In addition, IVUS can be used to directly measure the LRV’s diameter at the site of compression and in the areas adjacent to it to best size the LRV for subsequent stenting (Fig 2).2 Nonoperative treatment of NS. Patients with mild symptoms including microscopic hematuria and orthostatic proteinuria can be managed nonoperatively.17,18 A nonoperative approach is also preferred in patients younger than 18 years. In this population of young patients, the increase in intra-abdominal and fibrous tissue at the SMA origin during growth releases the obstruction
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of the LRV from the fork formed between the SMA and the aorta.2 Moreover, conservative management with emphasis on weight gain increases the retroperitoneal adipose tissue, leading to a change in the positioning of the left kidney with reduction of tension on the LRV; this approach has been shown to resolve symptoms of NS in 30% of patients.2,4 Treatment with agents such as angiotensin-converting enzyme inhibitors and aspirin has been used to improve orthostatic proteinuria and renal perfusion.2 Wang et al14 described 16 patients treated nonoperatively, with clinical improvement in 11 (68.7%). Total and partial relief of symptoms occurred in two and nine patients, respectively. No relief was observed in five (31.2%) patients, proving that conservative management was effective in two-thirds of patients in this group. Open surgical treatment of NS. Many experts consider the open surgical approach the standard of care for the treatment of NS, including techniques such as LRV transposition, nephropexy, renal autotransplantation, and gonadocaval bypass, among others. The main goal of the open surgical approach is to correct or to improve the LRV compression.14 The Mayo Clinic series4 preferred technique was LRV transposition with adjunctive great saphenous vein patch or cuff in selected cases to enlarge the narrowed LRV and to decrease the tissue tension between the LRV and the inferior vena cava (IVC). Early results (within 30 days) demonstrated no major perioperative complications, renal failure, or mortality, with an average length of hospital stay of 4.5 6 2.7 days. Three (8.3%) patients had recurrence of symptoms with demonstrable anatomic findings, including two LRV stenoses and one LRV occlusion that required angioplasty with stenting, mechanical thrombolysis, and open revision. Late results (>30 days) with a mean follow-up of 36.8 6 52.6 months demonstrated eight (22.2%) patients requiring endovascular and open reintervention due to seven LRV stenoses and one occlusion. Of the 11 patients who required reintervention, six (54.5%) underwent additional endovascular procedures. Primary, primary assisted, and secondary patency at 24 months was 74%, 97%, and 100%, respectively. Freedom from reintervention at 12 and 24 months was 76% and 68%, respectively. Four (11%) patients did not have resolution of their flank pain. Hohenfellner et al19 evaluated the outcomes of LRV transposition in eight patients. Postoperative complications included deep venous thrombosis, retroperitoneal hematoma necessitating surgical revision, and paralytic ileus in one patient each. On long-term follow-up, one patient required laparotomy for mechanical ileus 4 years after the procedure. Seven (87.5%) patients had resolution of symptoms. One patient underwent nephrectomy 6 years after the initial procedure because of persistent periureteral venous varicosities. Wang et al14 treated 23 patients with NS. Seven (30.4%) patients underwent LRV transposition, and the
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remaining 16 (69.5%) patients were managed nonoperatively. Three (42.8%) patients had postoperative complications, including paralytic ileus in two patients and one surgical revision as a result of retroperitoneal hematoma. Hematuria and proteinuria ceased 5 to 14 days after the surgical intervention, and pelvic pain resolved in all patients except one. There was no outflow obstruction determined by DUS and no abnormalities in urine test during follow-up (24-84 months). Kim et al20 and Ullery et al21 described five patients treated with LRV transposition. Intraoperatively, they recommend the Kocher maneuver over the division of the ligament of Treitz for improved exposure at the time of LRV transposition. On follow-up, all patients had resolutions of symptoms and remained free of reintervention at 13 months. LRV transposition corrects the compression at the aortomesenteric angle by moving the confluence of the LRV to the IVC caudally by 3 to 5 cm.14 However, it does not resolve the additional etiopathogenic mechanics, such as the left kidney ptosis with stretching of the LRV over the aorta.13 Thus, renal autotransplantation has been advocated as a solution for NS. It arguably resolves not only the compression between the SMA and the aorta but also the problem with the posterior location of the left kidney.22 Ali-El-Dein et al13 treated six patients with renal autotransplantation for anterior NS. Complete resolution of hematuria and pain occurred in all patients. Therefore, they recommended renal autotransplantation for the treatment of anterior NS and LRV transposition for posterior NS. Salehipour et al22 also implemented renal autotransplantation for the treatment of NS in four patients. Postoperatively, hematuria resolved, and on renal scans, there was excellent perfusion without any ureteral obstruction. Other procedures have been suggested and proposed in the literature, such as LRV ligation and iliac vein bypass,23 SMA transposition, nephropexy with excision of varicosities, and gonadocaval bypass, with excellent outcomes; however, the number of patients treated was limited2 (Table). Minimally invasive laparoscopic treatment of NS. In addition to the open surgical approach, laparoscopic techniques have been developed as a less invasive option for the management of patients with NS. Wang et al24 evaluated the outcomes of 13 patients using this technique of laparoscopic extravascular stent placement. This technique included the placement of an externally reinforced expanded polytetrafluoroethylene graft (Bard Peripheral Vascular, Tempe, Ariz) of 10 mm in diameter. Subsequently, the graft was then bound to the surface of the LRV to prevent compression. Postoperatively, both DUS and cross-sectional imaging demonstrated excellent blood outflow of the LRV. Complete resolution of symptoms was noted in 77% of patients, and an
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Table. Open, minimally invasive, and endovascular series presenting the management of nutcracker syndrome (NS) Author Erben et al4
No. of patients 37
Technique Open (LRV transposition) and endovascular
Outcomes and complications Reintervention d
d
Wang et al14
23 (7 had surgery) Open (LRV transposition) and conservative
d
d
Ali-El-Dein et al13
11
Open (autotransplantation)
d
d
Hohenfellner et al19
8
Open (LRV transposition)
d
d
Follow-up, months
11
1-219
1
14-122
None
12-120
3/8 had postoperative complications All except one had resolution of symptoms
2
41-136
No major complications postoperatively Resolution of symptoms in 33 of 37 patients 3/7 had postoperative complications All except one had resolution of symptoms Complete resolution of pain in all patients except one Hematuria resolved in six patients and improved in two
Salehipour et al22
4
Open (autotransplantation)
d
Hematuria was resolved in all patients
None
4-24
Ullery et al21
3
Open (LRV transposition)
d
All had resolution of symptoms
None
13
Gong et al23
3
Open (spermatic vein ligation and iliac vein anastomosis)
d
3 months after the procedure, patients showed improvement in their sperm and disappearance of proteinuria
None
3
Kim et al20
2
Open (LRV transposition)
d
All had resolution of symptoms
None
1-42
Laparoscopic
d
Complete symptom relief in 77% Partial relief in 15% Recurrent hematuria in 7.6%
None
8-52
Complete relief of symptom in two patients Partial relief in one patient
None
16-37
d
Evaluation of rate of stent migration; five patients had stent migration to the IVC, right side of the heart, and left side of the LRV
3
6-126
d
Improvement of symptoms in 59/61 patients 3/61 patients had postoperative complications
2
12-144
Wang et al24
13
d d
Zhang et al17
3
Laparoscopic
d
d
Wu et al26
75
Endovascular 68 SMART Control 7 Wallstents
Chen et al27
61
Endovascular 45 SMART Control 15 Wallstents 1 Palmaz stent
d
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Table. Continued. Author Wang et al25
No. of patients 30
Technique
Outcomes and complications Reintervention
Endovascular SMART Control
d
d
Li et al9
6
Endovascular Protégé stent
d
d
d
Follow-up, months
Technical success was achieved in the entire cohort 2/30 had postoperative complications
None
12-80
No recurrence of gross or microscopic hematuria was seen in five patients Two patients had complete remission of left varicocele Three patients were free from left flank pain
None
6-60
Basile et al28
3
Endovascular Self-expandable nitinol stents
d
Resolution of symptoms at 12- to 24-month follow-up
None
14-18
Chen et al18
3
Endovascular Self-expandable
d
Resolution of hematuria
None
24 and 36
Baldi et al29
2
Endovascular SMART Control
d
No perioperative complications Resolution of hematuria
None
12 and 24
d
IVC, Inferior vena cava; LRV, left renal vein.
additional 15% of patients reported partial resolution of symptoms. Migration of a stent was present in one patient, who presented postoperatively with recurrence of gross hematuria. Zhang et al17 reported three cases of patients treated with laparoscopic extravascular stent placement. There were no procedural and postoperative complications. On DUS, there was smooth blood outflow, decrease in flow velocity, and reduction in the diameter of the gonadal vein varices. Complete and partial relief of symptoms was achieved in two patients and one patient, respectively. Microhematuria was noted in one patient during follow-up (16-37 months; Table). Endovascular treatment of NS. Since the advent of endovascular interventions, these techniques have also been applied to the treatment of NS.25 Endovascular treatment has been an appealing alternative to open procedures because of its minimally invasive nature; however, its major drawback is the lack of studies with long-term follow-up. Wu et al26 presented the largest series, which evaluated and treated 75 patients. They used 68 SMART Control stents (Cordis, Milpitas, Calif) and seven Wallstents (Boston Scientific, Marlborough, Mass) for their interventions. Five (6.6%) patients presented with stent migration in the postoperative period, including two into the IVC and one each to the right ventricle, right atrium, and distal to the LRV.
Chen et al27 evaluated the use of endovascular stents in 61 patients. The stents used in their series included 45 SMART Control stents, 15 Wallstents, and one Palmaz stent (Cordis). There were two procedural complications that required open surgical intervention, including open heart surgery, because of stent migration into the right atrium. Symptom improvement occurred in 59 (96.7%) patients by 6 months. On follow-up, two patients were noted to have recompression of the LRV by the SMA and the aorta despite the presence of a stent. Wang et al25 treated 30 patients endovascularly. Their preferred stent was the SMART Control stent. Technical success was achieved in the entire cohort without any complications. On follow-up, patients’ symptoms demonstrated improvement, and DUS demonstrated the absence of stenosis, good flow, and patency of all stents. Furthermore, Li et al9 evaluated the outcomes of six patients treated with self-expandable stents. After the procedure, they noted an increase in the diameter of the LRV and a decrease in the pressure gradient to
