Objectives: Nutcracker syndrome is rare, and a proportion of patients with this syndrome continue to have intractable pain and symptoms. Due to the heterogeneity of patients’ chief complaints and symptoms, the surgeon’s preferred approach may be inherently different but is of paramount importance to the outcome.
Materials and Methods: We present 4 cases in which renal autotransplant with extraction and ligation of previously placed gonadal coils was performed following previously attempted renal vein stenting or combined renal vein transposition followed by renal vein stenting.
Results: Autotransplant resulted in flank pain reso-lution with improvement in symptoms associated with pelvic congestion syndrome.
Conclusions: The approach to such cases requires meticulous and adequate vena cava exposure, with preparation for potential caval reconstruction. No firm inferences can be made from such a small series; however, we believe in renal autotransplant as first-line therapy, and failure after an initial renal vein stent should be salvaged by renal autotransplant over further endovascular attempts.
Key words : Flank pain, Nephrectomy, Pelvic congestion syndrome
Nutcracker syndrome (NCS) refers to the constellation of symptoms related to the compression of the left renal vein.1 This syndrome may produce symptoms of flank pain, microhematuria or macrohematuria, and orthostatic proteinuria and symptoms of pelvic congestion syndrome, which includes dysmenorrhea, dysuria, dyspareunia, and vulvar and pelvic varices in female and varicoceles in male patients.2 It more commonly affects females and may render them with incapacitating symptoms.3 Since its original des-cription, multiple variants of the syndrome have been described,4-7 with several diagnostic criteria evolving over the years to include Doppler ultrasonography, computed tomography (CT), magnetic resonance imaging, venography, and intraoperative modalities.8,9 The management of NCS includes the conservative approach, open and laparoscopic surgical procedures, and endovascular procedures. The commonest 2 surgical procedures are renal vein transposition and renal autotrans-plantation, with an armamentarium of alternative procedures, including proximal testicular-iliac-saphenous anastomosis (involving the use of the saphenous vein as a conduit to link the testicular and iliac veins), gonado-caval bypass, peri-pelvic varicosity excision, renocaval venous bypass, laparoscopic extravascular stent implantation, and renal decapsulation. When all else fails, and symptoms persist, nephrectomy may be considered.
More recently, the endovascular approach, renal vein stenting, has gained much popularity. Similarly, since pelvic venous congestion can be a sequela of NCS, patients may concomitantly have gonadal vein embolization/coiling. Due to a paucity of data on long-term follow-up and lack of consistency in the approach to NCS, proposing guidelines is cumbersome; hence, the appropriate procedure is often left to the discretion of surgeons and their experience. Here, we present a series of challenging cases referred to us with persistent symptoms of NCS following renal vein stenting with or without gonadal vein embolization/coiling. We discuss the safety of renal autotransplantation, the technical intricacies, and lessons learned on patient selection.
Materials and Methods
Our study includes the presentation of 4 cases and the short-term follow-up. Full informed consent was obtained from the patients and their legal guardians.
Case 1, a 23-year-old female with a history of left flank pain and symptoms of pelvic congestion syndrome, was diagnosed with NCS, which had been confirmed with CT findings. Her past medical history was also notable for endometriosis and May-Thurner syndrome and scoliosis of her thoracic spine. She subsequently underwent left renal vein transposition, which alleviated her pain for approximately 1 month until it recurred. A venogram was performed, demonstrating a small thrombus; hence, thrombectomy and renal vein stenting were performed. Unfortunately, she required restenting (stent-in-stent) for stent fracture, during which she also had coil embolization of her left gonadal vein. Despite all, her flank pain and symptoms returned approximately 16 months later.
The patient sought consultation at our center, and, following a thorough and informed consent process and evaluation by gynecology and vascular surgery, she elected to undergo renal autotransplant, with removal of stents and ligation/excision of her gonadal vein and coils. The initial approach involves total mobilization of the vena cava above and below the renal vein, with ligation of the lumbar veins, and exposure of the contralateral renal vessels. A Satinsky clamp was placed below the level of the stents in a side-biting manner on the cava, and an elliptical incision was made at the junction of the renal vein and vena cava. Using a spatula to dissect the stent off the caval wall, we extracted both stents along with the kidney. The edges of the vena cava were then sewn using 4-0 Polypropylene with minimal narrowing. After excision of the stent from within the renal vein (Figure 1), we implanted the kidney into the right iliac fossa in a standard manner on the common iliac vein and artery, with a modified Lich-Gregoir ureteroneocystostomy. The left gonadal vein along with the coils was excised entirely.
Case 2 was a 38-year-old female patient who had renal vein stenting and bilateral coil embolization of her pelvic veins at an outside institution. Her past medical history was notable for celiac disease and ankylosing spondylitis. The history entailed initial development of left pelvic pain 6 months after giving birth. Initial work-up was concerning for pelvic congestion syndrome; hence, she had initially underwent embolization of her pelvic veins. It was after this embolization that her left flank pain escalated. She had further embolizations in attempts to alleviate the pain, and, in the process, additional work-up (CT with contrast) demonstrated left renal vein compression, leading to diagnosis of NCS. She then underwent renal vein stenting; however, despite subsequent imaging demonstrating patency of the stent, the pain recurred 12 months later.
After consultation with rheumatology to ensure the pain was not attributable to her ankylosing spondylitis, she elected to undergo renal auto-transplant. Similar to case 1, full exposure of the vena cava was initially performed, followed by partial clamping of the cava and suture closing of the edges to ensure that there was no luminal narrowing.
After excision of the remainder of the stent in the renal vein, we implanted the left kidney into the right iliac fossa in a standard manner on the common iliac vein and artery, with a modified Lich-Gregoir uretero-neocystostomy. We then excised/ligated bilaterally the gonadal and pelvic veins that were previously embolized (Figure 2).
Case 3, a 16-year-old female with refractory pain and inability to cope, leading to deterioration in her school performance, was referred to us for further management. She was diagnosed with NCS based on symptoms of left flank pain, hematuria, and pelvic congestion syndrome. Her past medical history was notable for endometriosis, Hashimoto thyroiditis, depression, anxiety, and asthma. Fourteen months earlier, she had left renal vein stenting and left pelvic vein embolization. She had undergone extensive work-up, counseling, and psychiatric evaluation. A CT scan performed at our institute showed patency of the stent; however, there was clear extrusion of the stent through the anterior wall of the vena cava (Figure 3). After thorough consent, we proceeded with renal autotransplant.
After total mobilization of the vena cava as described earlier, we proceeded in the manner of clamping the vena cava below the left renal vein, clamping the contralateral renal vein, and clamping the vena cava above the left renal vein. After ligation of the left renal artery, we excised the left vein with a cuff of the vena cava where the stent was extruding. Using sharp scissors, we carefully dissected the stent off the posterior cava wall. After the kidney was extracted, we assessed the defect in the vena cava and proceeded with performing an elliptical patch venacavaplasty using bovine pericardium (BP) (Figure 4). We elected to implant the kidney on the ipsilateral side (left) on the external iliac vein, with end-to-end arterial anastomosis to the left internal iliac artery, and a pyelovesicostomy was performed.
Case 4, a 36-year-old female with refractory left flank, pelvic, left leg, and inner thigh pain, had undergone left renal vein transposition, followed by stenting of the transposed renal vein, angioplasty of the stent, and embolization of her left gonadal vein. On presentation, she was on multiple analgesics and occasional medical marijuana and reported worsening pain after the procedures. This case, similar to Case 3, required extensive mobilization of the vena cava with ligation of the lumbar veins. However, because the renal vein was transposed, dissection and exposure of the contralateral renal vasculature were not necessary.
After mobilization and clamping of the vena cava above and below the renal vein, a longitudinal venotomy of the vena cava was performed, with direction toward the renal vein ostium. Using sharp scissors, we dissected the stent off the caval walls and lifted it from the inside and off the renal vein ostium. After extraction of the kidney, we closed the longitudinal venotomy in continuum with the renal vein ostium, ensuring that luminal narrowing would not be encountered (Figure 5). This patient was also found to have severe narrowing of her left common iliac vein secondary to compression by the right common iliac artery (May-Thurner syndrome). Because this patient also had leg pain and pain radiating down the thigh, we elected to repair the narrowing. We mobilized the common iliac veins bilaterally and encircled them. We then proceeded in the manner of clamping the right common iliac vein, the left common iliac vein proximal to the narrowing, and the vena cava above the bifurcation. We per-formed a longitudinal venotomy over the narrowing, and sutured in a BP patch to create a wider lumen of the left common iliac vein. The left gonadal vein was ligated and excised along with the coils. We then proceeded with autotransplant on the right common iliac vein and artery, with a modified Lich-Gregoir ureteroneocystostomy.
All patients had near complete resolution of their flank pain; however, symptoms of pelvic congestion syndrome improved but were not completely resolved in most patients.
For case 1, her immediate postoperative course was uneventful, and, at the 7-month follow-up, her left flank pain had resolved. However, her symptoms associated with pelvic congestion syndrome had persisted, and she has been coping with pelvic floor muscle physiotherapy and minimal analgesics.
Case 2 had a complicated postoperative course with bowel obstruction, requiring a relaparotomy after failure of conservative management; however, no clear cause was identified. At the 8-month follow-up, her left flank pain and pelvic pain had resolved, and the patient was back to her normal baseline activities before the constellation of symptoms had started.
Case 3 also had a complicated postoperative course, with prolonged hospital stay due to pain related to her incision and lower gastrointestinal bleeding secondary to hemorrhoids, related to chronic opioid-induced constipation. At 6-month follow-up, her flank pain had improved dramatically; however, the pelvic pain persisted but was controlled with minimal oral analgesics. She was able to return to school, with resumption of her previous normal activities. Continued counseling was required in this case in liaison with her pediatric caregivers.
Case 4 had an uneventful postoperative course. On last follow-up at 7 months, her flank pain and thigh pain had resolved; however, she still required oral analgesics for her pelvic pain.
The diagnosis of NCS should be considered on the basis of careful clinical examination in patients with left flank pain, hematuria, and symptoms of pelvic congestion syndrome. Inherent to the paucity of data on outcomes, the procedure of choice remains biased by the surgeon’s experiences and preference. We strongly believe in autotransplant as first-line treatment; in congruence with other centers,10-12 we have found the success rate and pain resolution rates superior. In this small series of patients, we have demonstrated the safety and success of renal autot-ransplant following failed attempts at endovascular stenting and combined endovascular stenting/renal vein transposition. However, the approach to the vena cava entails principles learned from abdominal transplant and advanced oncology cases.
The critical steps for autotransplant include (1) an adequate incision via a midline approach rather than a chevron, as autotransplant is then more facile; (2) exposure of the major vessels via Cattel-Braasch and Mattox maneuvers, with kocherization of the duodenum; (3) ligation of the lumbar veins using silk ties, avoiding clips that may obscure vascular clamps, to adequately manipulate the vena cava at the level of, above, and below the stented renal vein and the contralateral renal vessels; (4) encircling of the vena cava with vessel loops; and (5) ensuring that BP is available in the operating room, as inferior vena cava (IVC) reconstruction may be necessary. If IVC clamping is required, after the caval venotomy is made, careful extraction of the stent is vital in light of the ensuing endothelial hyperplasia and tethering to caval walls.
We have found that use of BP is helpful in reconstructing the IVC. The safety of BP has been demonstrated extensively in cardiac and vascular procedures for arterial patching. Data comparing BP to other graft types have shown a lower rate of restenosis with BP and equivalent rates of post-operative bleeding, infection, and pseudoaneurysm formation.13-15 Data have also shown superior hemostasis with BP and suitability of BP as a vascular graft in infected fields when necessary.16,17
Although our goal was to embark on the fea-sibility and technical aspects of this approach in patients with previous interventions, it is paramount to emphasize the importance of patient selection. The setting of expectations is key with patients who have had long-standing debilitating pain, multiple previous procedures, and a sense of lost hope. Pertinent to this challenging patient population that we have been encountering is the approach to their diagnosis and the management thereafter. Nutcracker syndrome is a rare disease, with paucity of data on its true prevalence and long-term outcomes.
Loin pain hematuria syndrome, another master of disguise, may overlap with NCS or may be the umbrella overlying NCS in a minority of cases. Similarly, patients with classic symptoms of flank pain, hematuria, and orthostatic hematuria are not identical to those who also have severe symptoms of pelvic congestion syndrome. This is important to highlight, as we believe that the flank pain incurred may not be purely secondary to venous hyper-tension; rather, it may be combined with its related perirenal and periureteric varicosities, perhaps contributing to long-standing urothelial irritation and ureteral spasm.
We have previously described the utility of ureteric bupivacaine instillation in a selection of patients, highlighting that, if patients respond, the pain would most likely resolve with autotransplant. This may further explain why reoperating and performing renal autotransplant results in resolution of flank pain but has mild to moderate effects on the associated pelvic congestion syndrome-related pain, or, rather, due to long-standing congestion, the pelvic pain becomes irreversible or centrally driven.
Before embarking on the success of renal auto-transplant, we must highlight the rationale for the endovascular approach and renal vein transposition. Naturally, a minimally invasive, incision-free ap-proach would be the most appealing. However, we have witnessed patients with persistent symptoms beyond the widely published follow-up intervals on outcomes after renal vein and pelvic vein stenting/embolization. In the largest series of 75 patients,18 the authors used 68 SMART Control Stents (Cordis, Milpitas, CA, USA) and 7 Wallstents (Boston Scientific, Marlborough, MA, USA) for their inter-ventions. Five patients presented with stent migration in the postoperative period, including 2 into the IVC and 1 each to right ventricle, right atrium, and distal to the left renal vein. Similarly, in a series of 61 patients19 (1 Palmaz, 15 Wallstents, 45 SMART Control Stents), symptom improvement, not resolution, occurred in 59 patients (96%) at 6 months after treatment, with 2 patients requiring open heart surgery for stent migration to the right atrium. Clearly, the outcomes appear favorable; however, these are short-term solutions, and serious morbidity can occur in 3% to 7% of the cases.
Experts in the field consider renal vein trans-position as the criterion standard open approach. In the largest series by the Mayo clinic,6 early results (< 30 days) demonstrated no major perioperative complications or mortality. Three patients (8.3%) had recurrence of symptoms with demonstrable ana-tomic findings, including 2 left renal vein stenoses and 1 left renal vein occlusion that required angioplasty with stenting, mechanical thrombolysis, and open revision. Late results (> 30 days) with a mean follow-up of 36.8 ± 52.6 months demonstrated 11 patients (30%) who required reintervention either with endovascular stenting and/or open reinter-vention due to left renal vein stenosis or occlusion. Freedom from reintervention at 12 and 24 months was 76% and 68%, respectively. Four patients (11%) did not have resolution of their symptoms despite all treatments. Of note, renal vein transposition corrects the compression at the aorto-mesenteric angle; however, it does not correct the additional mechanics such as renal ptosis with stretching of the renal vein over the aorta.10
The approach to management of NCS remains at the discretion of the surgeon and the center’s experience. Minimally invasive approaches will inherently remain appealing. However, because patients are heterogenous with respect to their presenting symptoms and chief complaints, a standardized approach is cumbersome to adapt. We acknowledge that, due to the small number of patients in our series, no firm inferences may be made; however, we believe in renal autotransplant as first-line treatment and that failure after an initial renal vein stent should be salvaged by renal autotransplant versus further endovascular attempts.
DOI : 10.6002/ect.2019.0015
From the 1Department of Surgery, Division of Transplantation, University of
Wisconsin, Madison, Wisconsin, USA; and the 2Department of Surgery, Division of
Transplantation, University of Maryland, Baltimore, Maryland, USA
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Talal Al-Qaoud, University of Maryland, Department of Surgery, Division of Transplantation, 29 South Greene Street, Suite 200, Baltimore, MD 21202, USA
Phone: +1 6084222456
Figure 1. Renal Vein Stent After Extraction
Figure 2. Extraction of Coils From Gonadal Veins Followed by Suture Ligation and Excision
Figure 3. Extrusion of Renal Vein Stent Through the Anterior Wall of the Vena Cava
Figure 4. Elliptical Excision of Renal Vein With Vena Cava Cuff, Followed by Bovine Pericardial Venacavaplasty
Figure 5. Longitudinal Caval Venotomy Toward Renal Vein Ostium, With Continuous 4-0 Polypropylene Suture Closure