Sonographic Diagnosis of Anterior Nutcracker Phenomenon and its Prevalence in Nigerian Males with Varicoceles

Abstract

Background:

The nutcracker phenomenon (NCP) is a rare and often unrecognised cause of varicocele, haematuria, and chronic pelvic pain due to the left renal vein (LRV) compression between the aorta and the superior mesenteric artery (anterior nutcracker). Its varied clinical manifestations make the diagnosis difficult and usually delayed. A high index of clinical suspicion, with appropriate imaging studies is crucial for the diagnosis.

Objectives:

We used a colour Doppler ultrasound scan to investigate the anatomic and haemodynamic properties of testicular and renal venous drainage. The emphasis was to determine the presence or absence of NCP, its possible effects on varicocele formation and severity, and its relationship with the body mass index (BMI) of the subjects.

Materials and Methods:

We carried out Doppler scrotal and upper abdominal ultrasound examinations of 100 subjects with male infertility and clinical varicoceles (group A), and 100 controls with male infertility but without varicoceles (group B). The mean peak velocity (PV) and the anteroposterior (AP) diameters of different segments of the renal veins, as well as the diameters of the testicular veins of the subjects in the two groups were measured and compared. The ratios of the PV and the diameters between the hilar portion and the aorto-mesenteric portion of the LRV were also calculated and compared. A PV ratio or anteroposterior diameter ratio between the two portions greater or equal to 5.0 was considered diagnostic of NCP. The diagnosis of varicocele was confirmed by visualising a dilated pampiniform plexus vein measuring greater than 2 mm in diameter using an ultrasound scan.

Results:

Six out of 100 subjects in group A had diameter and PV ratios (≥5.0) in the LRV that suggested the presence of NCP, and all participants in group B had neither diameter nor PV ratio suggestive of NCP. The prevalence of NCP seen within the varicocele group in this study was statistically significant (P = 0.038). Five (83.3%) of the six subjects in the NCP-associated varicocele subgroup had microscopic haematuria, orthostatic proteinuria, or both; these qualified them for the diagnosis of nutcracker syndrome (NCS), A significantly lower mean BMI (P = 0.004) was noted among the NCP-associated varicocele subgroup compared to those without NCP.

Conclusion:

Our findings indicate that the NCP is a significant finding in patients with varicoceles in our environment, and it is more common with lower BMI.

Introduction

Varicocele is the abnormal dilatation, elongation, and tortuosity of the network of veins draining the testes. Varicocele is more prevalent among infertile men (35%–40%) when compared with the general population (15%), and it is an established correctable cause of male infertility in Nigeria, and worldwide.[1,2,3,4] The anatomical compression of the left renal vein (LRV) between the abdominal aorta and superior mesenteric artery (SMA) which may cause the classic clinical triad of haematuria, varicocele, and left flank pain was first described by El Sadr and Mina[5] in 1950. This meso-aortic entrapment of the LRV without associated clinical symptoms, termed the “nutcracker phenomenon” (NCP) by De Schepper[6] in 1972 is a proposed aetiology of varicoceles. When NCP causes symptoms, it is termed as NCS.[7,8,9,10,11,12]

The common symptoms of NCS include haematuria, orthostatic proteinuria, abdominal pains, varicoceles, and infertility in males; dysmenorrhoea, dyspareunia, pelvic pains, and varices in the vulva or thigh in females. A high index of suspicion is usually required to diagnose this uncommon condition in patients presenting with the symptoms.[8,9,10]

Several imaging studies have been used to evaluate patients with suspected NCS. These include Doppler ultrasonography, CT angiography, magnetic resonance angiography, and retrograde venography. Selected left renal venography with reno-caval pressure gradient determination is the standard for the diagnosis of the NCP, but it is an invasive procedure with inherent potential for significant morbidity and possible mortality. Doppler ultrasound scan (DUS) is a noninvasive, non-ionising, cheaper, readily available alternative, but equally effective imaging modality for identifying NCP.[10,11,12,13,14,15,16] Researchers have suggested various DUS diagnostic criteria for NCP using the ratio of peak velocity (PV) at the aorto-mesenteric to that at the hilar portions of LRV along with the ratio of the corresponding diameters of LRV. The recommended ratios for the diagnosis of NCP range from 4.0 to 5.0, and they have high sensitivity and specificity.[12,13,14]

Our literature search yielded only a case report on NCP/NCS from the West African sub-region.[9] Even though the prevalence of this condition is not known, it may be more common than suspected.[16] Our study was done to add to the sparse existing body of knowledge on the subject from our region. The aim of this prospective comparative study of two groups of infertile Nigerian males with and without clinical varicoceles was to determine and compare the haemodynamic parameters of their testicular and renal venous drainage using DUS. Our objectives were to determine if NCP was significantly present among them and to evaluate the possible effects of their relevant renal haemodynamic parameters on the formation and severity of varicoceles. We also sought to determine any influence of the body mass index (BMI) of the subjects on the occurrence of NCP.

Materials and Methods

This was a prospective, observational, and comparative study between infertile male patients with clinical varicoceles and infertile male patients without varicoceles. Approval for the study was obtained from the Research and Ethical Committee of our institution before the commencement of our study. Informed consent was obtained from each of the subjects and documented before their enrollment as participants in the study.

A total of 200 consenting patients comprising 100 infertile males with clinical evidence of unilateral or bilateral varicoceles (group A) and 100 age-matched infertile males without varicoceles (group B) were recruited from the urology outpatient clinics of our hospital. The infertile male patients were determined by their clinical history of inability to father a child despite regular sexual intercourse with their wives for periods lasting more than a year, and also from their seminal fluid parameters that fell below the lower reference limits of World Health Organization.[17] Patients with pyelonephritis, heart or renal failure, the presence of a mass in the renal parenchyma, previous surgical treatment for varicocele, epididymitis, orchitis, and those with other scrotal masses were excluded from the study.

All sonographic examinations were performed using a real-time ultrasound machine (Toshiba Nemio XG diagnostic Ultrasound System). Inter-observer variability was eliminated by allowing only one radiologist to perform all the scans, while intra-observer variability was reduced by taking an average of three measurements for each parameter.

Scrotal Doppler ultrasound examination was performed on each subject in both supine and erect positions with a 10 MHz linear transducer, to confirm and grade the varicocele using Sarteschi’s grading system.[18] The sonographic diagnosis of varicocele was made by visualising dilated pampiniform plexus of veins measuring more than 2 mm in diameter as used in previous studies.[11,18]

Ultrasonography of the renal veins was done with the patient in the supine position using a convex 5 MHz curvilinear transducer. Patients were required to fast for 6–8 h to reduce bowel gas overlying the renal vessels. The anteroposterior (AP) diameters of the LRV at its aorto-mesenteric portion (where it crosses between the aorta and the SMA), and at the renal hilum were measured in millimetres. The measurements for peak velocities in the same segments of the LRV were also taken in centimetres per second. The PV was measured in the transverse plane at the two points in the LRV; PV1 near the hilum and PV2 at the aorto-mesenteric portion. The ratio of the PV in the LRV at the two portions (PV2/PV1) was calculated for each subject. The ratio of the diameters of the LRV at the hilar portion to its diameter at the aorto-mesenteric portion was also calculated. The criteria used to diagnose NCP were the ratio of diameters of Hilar to SMA segments of the LRV ≥5, and the SMA-Hilar segment PV ratio of ≥5. The AP diameter of the right renal vein (RRV) was measured at the mid-segment in millimetres. PV in the RRV was also measured at the mid-segment in centimetres per second.

Subjects with renal vein Doppler parameters diagnostic of the NCP all had urinalysis to check for microscopic haematuria and proteinuria. Such subjects were requested to submit midstream early morning urine and midday samples for urinalysis with dipsticks. The absence of protein in early morning urine and its presence in the midday urine samples on dipsticks were diagnostic of orthostatic proteinuria. Haematuria was also diagnosed based on positive dipsticks in both samples. The BMI for each subject was calculated and recorded as weight in kilograms divided by height squared in metres.

The data collected were analysed using Standard Statistical Package for Statistical Package for Social Science (SPSS®) for Windows, version 20.0.0 17.0.1; 2011. Categorical variables such as demographics, BMI, and the presence of NCP were compared in the case and control populations using Chi-square. Continuous variables such as pampiniform plexus diameters and renal vein Doppler parameters were compared in the case and control populations using the Student t test. Pearson correlation coefficient (r) was used to measure the linear relationship between pampiniform plexus diameter and renal vein Doppler parameters. Spearman’s rank-order correlation was used to measure the relationship between varicocele grades and renal vein Doppler parameters. P value <0.05 was considered significant.

Results

Subjects’ demography

A total of 200 subjects consisting of 100 with clinical varicoceles (group A) and 100 without varicoceles (group B) were enrolled in the study. The two groups were equally matched for age with mean ages of 39.00 ± 6.63 years and 38.27 ± 5.63 years, respectively, for the participants in the two groups (P < 0.9; t = 0.103). The mean BMI for the subjects with clinical varicocele was 25.5 ± 4.2 while that of those without varicocele was 24.5 ± 2.1 (P = 0.038, χ² = 7.426).

Types and mean diameters of varicoceles

Sixty-seven (67%) of the participants in group A had bilateral varicoceles, 31 people (31%) had isolated left varicoceles and only 2 people (2%) had isolated right varicoceles [Table 1]. The mean diameters of the right and left pampiniform plexuses (2.21 ± 0.68 mm and 3.05 ± 0.70 mm, respectively) in group A were significantly (P < 0.001) higher than the comparative diameters in group B (1.31 ± 0.22 mm and 1.49 ± 0.18 mm).

Table 1.

Distribution of varicoceles in group A

Affected sides	Frequency (N)	Percentage (%)
Total varicoceles (unilateral and bilateral)	100	100
Unilateral varicoceles (left or right)	33	33
Bilateral varicoceles (left and right)	67	67
Isolated left varicoceles	31	31
Total left varicoceles	98	98
Isolated right varicoceles	2	2
Total right varicoceles	69	69

Renal vein Doppler ultrasound parameters

The measured and calculated mean of DUS haemodynamic parameters of the renal veins diagnostic of NCP are shown in Tables 2 and 3. Six participants in group A had diameter and PV ratios of the LRV that suggested the presence of NCP (PV and or diameter ratios ≥5.0) while no participant in group B had neither a diameter nor PV ratio suggestive of NCP.

Table 2.

Mean of renal veins Doppler parameters in the participants

Parameters	Group A	Group B	t test	P value
Hilar diameter of LRV (mm)	8.42 ± 1.82	7.79 ± 1.31	−2.851	0.005
AMP diameter of LRV (mm)	4.59 ± 1.33	5.09 ± 0.93	3.048	0.003
Mid diameter of RRV (mm)	7.39 ± 1.52	6.53 ± 0.93	−4.835	<0.001
Hilar: AMP diameter of LRV	2.11 ± 1.20	1.61 ± 0.54	−3.814	<0.001
PV(hilar) of LRV (cm/s)	16.93 ± 5.68	14.89 ± 4.42	−2.837	0.005
PV(AMP) of LRV (cm/s)	32.06 ± 17.39	24.61 ± 7.66	−3.918	<0.001
PV of RRV (cm/s)	18.28 ± 7.96	15.88 ± 5.89	−2.424	0.016
AMP: Hilar PV of LRV	2.03 ± 1.10	1.71 ± 0.49	−2.683	0.008

Table 3.

Comparison of NCP diagnostic ratios in groups A and B

Parameters	Group A: N (%)	Group B: N (%)
PV ratio
<5.0	94 (94)	100 (100)
≥5.0 (NCP)	6 (6)	0 (0)
Test statistics: Yates corrected χ2 = 4.296, P = 0.038
Diameter ratio
<5.0	94 (94)	100 (100)
≥5.0 (NCP)	6 (6)	0 (0)
Test statistics: Yates corrected χ2 = 4.296, P = 0.038

Group A was sub-classified into NCP-associated subgroup AI (N = 6) and subgroup AII (those without NCP; N = 94). A significant difference (t = 0.988, P = 0.004) was noted between the mean BMI of subgroup AI (20.78 ± 2.01) and the mean BMI of subgroup AII (25.87 ± 4.13). Four (66.7%) subjects in subgroup A1 had microscopic haematuria and three (50%) had orthostatic proteinuria. Five (83.3%) of the six subjects in subgroup A1 had microscopic haematuria, orthostatic proteinuria, or both. There was no significant correlation between right and left pampiniform plexus diameters, their respective peak velocities, and the AP ratios in group A [Table 4]. Similarly, no significant correlation was seen between right and left varicocele grades and their respective peak velocities or PV and AP ratios. The relationship between the grades or severity of left varicoceles and the NCP diagnostic parameters is shown in Table 5.

Table 4.

Pearson correlation between left pampiniform plexus diameter, and NCP diagnostic criteria in group A

Left pampiniform plexus diameter
PV hilar			PV amp			PV ratio			AP diameter ratio
	P	N	r	P	N	r	P	N	r	P	N
0.02	0.87	100	0.18	0.08	100	0.15	0.13	100	0.14	0.17	100

Table 5.

Correlation between left varicocele grades and NCP criteria in subgroup AI (with NCP) and subgroup AII (without NCP)

Left varicocele grades
	Grade 1 N (%)	Grade 2 N (%)	Grade 3 N (%)	Grade 4 N (%)	Grade 5 N (%)	Total N (%)
PV ratio
≤5.0 (subgroup AI)	0 (0.0)	16 (17.4)	2 (2.2)	67 (72.8)	7 (7.6)	92 (100.0)
>5.0 (subgroup AII)	0 (0.0)	0 (0.0)	0 (0.0)	6 (100.0)	0 (0.0)	6 (100.0)
Test statistic: χ2 = 2.189, P = 0.534
AP diameter ratio
≤5.0 (subgroup AI)	0 (0.0)	16 (17.4)	2 (2.2)	67 (72.8)	7 (7.6)	92 (100.0)
>5.0 (subgroup AII)	0 (0.0)	0 (0.0)	0 (0.0)	6 (100.0)	0 (0.0)	6 (100.0)
Test statistic: χ2 = 2.189, P = 0.534

Discussion

Varicocele was mostly bilateral, but more common on the left side in our study while only 2% of the subjects had isolated right varicocele. These findings from our study are in agreement with previous reports.[1,2,3,4,19] The anatomical difference between the right and left testicular veins is responsible for the preponderance of varicoceles on the left. The right testicular vein usually drains directly into the IVC at an acute angle, while the left testicular vein drains indirectly into the LRV at a right angle.[3,6] One of the proposed aetiologies of left varicoceles is the anterior NCP. It usually occurs due to the compression of the LRV between the aorta and the SMA. This results in retrograde blood flow from the LRV into the left testicular vein.[11]

There were statistically significant differences between the mean peak velocities at the aorto-mesenteric (AMP) and hilar portions (P = 0.005 and P < 0.001), as well as between the mean hilar and AMP anteroposterior diameters (P = 0.005 and P = 0.003) of the LRV in group A when compared to those of the control group in this study. These findings were similar to those from earlier studies that have sonographically evaluated renal vein haemodynamics in subjects with varicoceles using similar parameters at the same locations in the LRV.[11,20,21] The calculated ratios of the mean diameters (hilar-SMA) and peak velocities (SMA-hilar) were also significantly higher (P < 0.001 and P = 0.008) in group A than in the control group. Kim et al.[12] also reported similar findings in their study of paediatric patients with varicoceles. The mean PV of RRV and the diameter of RRV were also significantly different (P = 0.016 and P < 0.001) in group A as compared to those of the control group. However, this finding was in contrast to that of Unlu et al.[11] who reported no significant difference in PV RRV between their varicocele and control groups. This difference could be due to disparity in the locations for measuring the peak velocities in the RRV from the two studies.

We diagnosed NCP in six subjects in group A using the same parameters as Kim et al.[12] However, there was no subject with sonographic features of the NCP seen in the control group. The prevalence of the NCP that was seen in the varicocele group in this study was statistically significant (P = 0.038), and this suggests that the phenomenon may be a factor in the aetiology of varicoceles in our subjects as proposed by others.[11] Kim et al.[12] also reported a significant but higher prevalence of NCS using similar but slightly lower cutoff values of >4.9 for both the diameter and PV ratios. They reported 8 out of 27 males with varicoceles as having NCP. Pallwein et al.[20] reported that the presence of LRV entrapment resulted in significantly higher rates of varicocele recurrence after surgical repair. Therefore, patients with varicoceles may benefit more from routine evaluation for the presence of NCP before surgical repair. This may help in reducing recurrence after varicocelectomy if the identified NCP is also appropriately addressed concurrently.

We observed no statistically significant correlation between the sonographic grading of left varicoceles and the PV ratios in the renal veins in group A (P = 0.534). This finding was in contrast to that of Unlu et al.[11] who reported a correlation between the diameter of the dominant draining vein and the mean peak velocities of the medial and lateral segments of the LRV. This dissimilarity could be due to the smaller sample size of 35 they used. We also did not observe any statistically significant correlation between the right pampiniform plexus diameter and the PV of RRV and their corresponding ratios in group A just like Unlu et al.[11] These findings do not support a direct association between renal vein haemodynamics and the severity of varicoceles, and are in keeping with an earlier report by Mohamadi et al.[21]

Six subjects in the varicocele group of our study had diameter and PV ratios of the LRV diagnostic of the presence of NCP. In addition, five of the six subjects also had microscopic haematuria, orthostatic proteinuria, or both. These abnormal findings from their urinalysis qualify them for the diagnosis of NCS.[12,13] NCS may be associated with substantial morbidity in the presence of recurrent left flank pains with or without severe anaemia, but its diagnosis is often missed or commonly delayed.[8] The wrong or delayed diagnosis may be because these common clinical symptoms and signs are nonspecific, and can thus mimic other clinical entities.[7] Therefore, a high index of clinical suspicion is usually required to diagnose NCS and consequently request the necessary investigations to confirm or exclude such clinical suspicion. Haematuria is usually the most commonly reported symptom of NCS and it was observed in four (66.7%) subjects in the n subgroup AI in this study. This is attributable to the rupture of thin-walled varices into the collecting system due to elevated venous pressure. It varies from micro-haematuria to gross haematuria which occasionally may result in significant anaemia requiring blood transfusions.[8,22] In the study by Shin et al.[14] the cause of isolated haematuria in their patients could not be identified by routine diagnostic protocols in 69% of cases. Forty percent of those with undiagnosed haematuria were later found to have NCP using renal Doppler ultrasonography.

A significantly lower BMI was noted among the subjects in the NCP-associated varicocele subgroup AI compared to those in subgroup AII in this study (P = 0.004). This finding was also in agreement with some earlier reports.[14,23,24] Accumulation of adipose tissue has been suggested to have a protective effect against the development of NCP. Fat deposition at the aorto-mesenteric area may likely serve as a cushion to prevent the compression of the LRV seen in NCP. Therefore, NCP may manifest following significant weight loss due to a decrease in retroperitoneal fat and resultant reduction in the aorto-mesenteric angle. Increased BMI was reported by Handel et al.[23] to be associated with a decreased prevalence of varicoceles. Shin et al.[14] also reported a significant inverse relationship between the PV ratio and BMI.

Many imaging methods including renal angiography, intravenous urograms, retrograde pyelograms, standard CT, and multiphasic CT urography have been used to diagnose NCP and NCS with various limitations and demerits.[8,9,10,11,12,13] Measurement of the pressure gradient between the LRV and inferior vena cava of 3 mm Hg or more, done using selective left renal venography is the gold standard for diagnosing NCP, but it is an invasive procedure.[25] DUS with the advantage of ready availability, convenience, and affordability is a reliable alternative to overcome the challenges commonly associated with other imaging techniques. However, DUS methods may also be limited by technical difficulties, including the limited or small sampling area during examination.[8,12]

Our study was limited in certain aspects which should be explored in further desired studies on this subject in our environment. Selective venography or any other reference standard was not used to confirm or exclude the diagnosis of the NCP. Furthermore, the Doppler haemodynamic parameters of the LRV parameters were measured by only one radiologist, and in only the supine position in all the patients.

Conclusion

The NCP was found to be significantly more prevalent among infertile males with varicoceles. Though higher renal vein Doppler parameters were found in the males with varicoceles, the findings did not support a direct association between the renal vein haemodynamics and the severity of varicoceles.

NCS may be an under-diagnosed clinical entity that deserves more attention in our environment. The presence of signs and symptoms of NCS should raise clinical suspicion for its diagnosis. Doppler ultrasonography is recommended as a screening and diagnostic test for NCP and NCS.

Author contributions

AOA: Contributed to concept and research design, data acquisition, analysis, and interpretation, drafting, and critical review of the manuscript. OMA: Contributed to the concept and research design, data analysis and interpretation, drafting, and critical review of the manuscript. ORW: Contributed to data acquisition and critical review of the manuscript. ARA: Contributed to concept and research design, data acquisition, and critical review of the manuscript. All authors read and approved the final manuscript.

Ethics approval

This work was reviewed and approved by the Health Research and Ethics Committee of the Lagos University Teaching Hospital (Approval No: ADM/DCST/HREC/APP/683).

Conflicts of interest

There are no conflicts of interest.

Abbreviations

• AA Abdominal aorta

• IVC Inferior vena cava

• LRV Left renal vein

• DUS Doppler ultrasound scan

• NCP Nutcracker phenomenon

• NCS Nutcracker syndrome

• RRV Right renal vein

• SMA Superior mesenteric artery

Funding Statement

Nil.