Sexuality and Body Image After Uterine Artery Embolization and Hysterectomy in the Treatment of Uterine Fibroids: A Randomized Comparison

In this paper the effect of uterine artery embolization (UAE) on sexual functioning and body image is investigated in a randomized comparison to hysterectomy for symptomatic uterine fibroids. The EMbolization versus hysterectoMY (EMMY) trial is a randomized controlled study, conducted at 28 Dutch hospitals. Patients were allocated hysterectomy (n = 89) or UAE (n = 88). Two validated questionnaires (the Sexual Activity Questionnaire [SAQ] and the Body Image Scale [BIS]) were completed by all patients at baseline, 6 weeks, and 6, 12, 18, and 24 months after treatment. Repeated measurements on SAQ scores revealed no differences between the groups. There was a trend toward improved sexual function in both groups at 2 years, although this failed to reach statistical significance except for the dimensions discomfort and habit in the UAE arm. Overall quality of sexual life deteriorated in a minority of cases at all time points, with no significant differences between the groups (at 24 months: UAE, 29.3%, versus hysterectomy, 23.5%; p = 0.32). At 24 months the BIS score had improved in both groups compared to baseline, but the change was only significant in the UAE group (p = 0.009). In conclusion, at 24 months no differences in sexuality and body image were observed between the UAE and the hysterectomy group. On average, both after UAE and hysterectomy sexual functioning and body image scores improved, but significantly so only after UAE.
Introduction
When hysterectomy looms as a definite treatment for fibroid related menorrhagia, women and their sexual partners often express their concern about negative effects of the operation on their sexual wellbeing [1–4]. Furthermore, the uterus is considered important for a woman’s self-image and sexual image and some women fear that they will be “less of a woman” to their sexual partners [2, 4, 5]. Therefore a hysterectomy may also interfere with the woman’s body image. These concerns may cause some women to choose alternative treatment options [5]. During the last decade, uterine artery embolization (UAE) has emerged as an alternative treatment for hysterectomy [6]. UAE has been investigated in several case series and three randomized controlled trials [7–13], but the advantage of UAE in terms of sexual wellbeing and body image in comparison to hysterectomy remains unknown, since randomized controlled trials on this subject are not available as yet. Randomized controlled data are preferential to nonrandomized data, since nonrandomized data tend to overestimate treatment effect and are prone to selection bias [14]. We initiated a randomized trial comparing UAE and hysterectomy and have published several short-term results previosly [15–17]. In the present paper, we compare changes in sexuality and body image in patients with symptomatic uterine fibroids who were randomly assigned to either UAE or hysterectomy.
Materials and Methods
Study Design
The details of our study design have been described elsewhere and are discussed here briefly [15]. The EMMY trial (EMbolization versus hysterectoMY) is a prospective randomized multicenter clinical trial with 28 participating hospitals in the Netherlands. Eligible patients met the following inclusion criteria: they were clinically diagnosed with uterine fibroids (confirmed by ultrasonography), had menorrhagia as the major complaint, were premenopausal, and had no wish to conceive. All patients were candidates for undergoing a hysterectomy: other treatment options either had failed, were undesired, or had provided unsatisfactory results.
Eligible patients were informed verbally and in writing about possible risks and benefits of both procedures, and were invited to participate in the trial. After written informed consent had been obtained, patients were randomly assigned (1:1) to UAE or hysterectomy by computerized randomization, stratified for hospital. The study was approved by the Dutch Central Committee Involving Human Subjects (www.ccmo.nl) and the local ethics committees of all participating hospitals.
Pre-assessment
All patients were assessed by the attending gynaecologist. Current symptoms and a complete medical and gynaecological history were recorded. All patients underwent a pelvic ultrasound to determine the number of fibroids and the size of the largest fibroid. Sociodemographic characteristics were assessed by means of a questionnaire.
Procedures
Uterine artery embolization
UAE was performed by an interventional radiologist. A catheter was introduced into the femoral artery and advanced over the aortic bifurcation to the contralateral internal iliac artery, and digital subtraction angiography was performed to identify the origin of the uterine artery. When catheters were placed correctly, the UAE was carried out. Polyvinyl alcohol (PVA) particles of 355–500 μm were used in all procedures. UAE patients were advised to refrain from sexual intercourse for at least 2 weeks and thereafter, depending on their complaints.
Hysterectomy
The type of hysterectomy and the route of access were determined by the gynecologist. The following procedures were allowed: abdominal hysterectomy, vaginal hysterectomy, laparoscopically assisted vaginal hysterectomy, and laparoscopic hysterectomy. Both supravaginal and total hysterectomies were allowed. After discharge hysterectomy patients were advised not to have sex until the first outpatient visit at 6 weeks.
Questionnaires
Sexual functioning and body image were assessed by means of patient questionnaires. At baseline, questionnaires were completed by all patients before randomization. Follow-up questionnaires were completed at 6 weeks and 6, 12, 18, and 24 months after treatment. The questionnaire consisted of the Sexual Activity Questionnaire (SAQ), the Body Image Scale (BIS), and the Mental Component Summary (MCS; as part of the Medical Outcome Study Short Form [MOS SF-36]).
The SAQ, originally designed to investigate sexual functioning in women treated with tamoxifen because of a positive family history of breast cancer [18], is also useful in women with nonmalignant gynecological disorders [19]. In Table 1 the SAQ is displayed. The questionnaire consists of three dimensions, and each dimension yields its own score: pleasure from sexual intercourse (desire, enjoyment, and satisfaction; score range, 0–18), discomfort during intercourse (score range, 0–6), and habit (frequency; score range, 0–3). Pleasure and habit are good with higher scores, while discomfort is worse with higher scores. The SAQ was only filled out by patients who were sexually active during the month before receiving the questionnaire.
Table 1The Sexual Activity Questionnaire (SAQ) and the Body Image Scale (BIS)SAQ Dimension pleasure  1. Was having sex an important part of your life in the last month?  2. Did you enjoy sexual activity in the last month?  3. Did you desire to have sex with your partner in the last month?  4. In general were you satisfied after sexual activity in the last month?  5. How often did you engage in sexual activity in the last month?  6. Were you satisfied with the frequency of sex in the last month? Dimension discomfort  1. Did you notice dryness of your vagina in the last month?  2. Did you feel pain or discomfort in the last month? Dimension habit  1. How did the frequency of sexual behavior in the last month compare with what is usual for you?BIS In the last month  1. Have you been feeling self-conscious about your appearance?  2. Have you felt less physically attractive as a result of your menstrual bleeding problem?  3. Have you been dissatisfied with your appearance when dressed?  4. Have you been feeling less feminine as a result of your menstrual bleeding problem?  5. Did you find it difficult to look at yourself naked?  6. Have you been feeling less sexually attractive as a result of your menstrual bleeding problem?  7. Did you avoid people because of the way you felt about your appearance?  8. Have you been feeling the treatment has left your body less whole?  9. Have you felt dissatisfied with your body?  10. Have you been dissatisfied with the appearance of your scar? Questions on the BIS shown in italics have been omitted
Furthermore, participating patients were asked to judge their current sexual life in two questions: “How would you describe the quality of your current sexual life?” and “How well can you live with your current sexual life?” One of the following responses could be ticked: “very good,” “good,” “moderately good,” “neither good nor bad,” “moderately bad,” “bad,” and “very bad.”
The BIS was designed in order to asses changes in body image among cancer patients [20]. The questionnaire was also found reliable and valid in women with benign gynecological conditions [21]. Table 1 displays the questions of which the BIS consists. Unfortunately, questions 2, 4, and 6 were not represented correctly in the questionnaire due to a translation error. Therefore we decided to omit these questions in order to attain a comparable outcome between groups. The BIS score ranges from 0 to 30. A higher BIS score indicates a worse body image.
In order to assess mental health before treatment as a predictor of worse sexual function after treatment, the MCS score of the 36-item MOS SF-36 was used [22]. This was done because bad preoperative mental health is associated with bad sexual life outcome [23].
Sample Size and Endpoints of the Present Study
The sample size was based on the primary endpoint of the clinical study, published elsewhere [24]: the elimination of menorrhagia in such way that hysterectomy could be avoided in the UAE group in at least 75% of patients within 2 years after the primary interventions.
The objective of the present study was to compare the following endpoints between both interventions: the number of sexually active patients, the scores yielded by the SAQ and the BIS, the subjective quality of sexual life. For this analysis, no separate power calculation was made.
Statistical Analysis
Data entry was performed using SPSS data entry for Windows 3.0. A random sample of 10% of the questionnaires was visually double checked by an independent second investigator, revealing a false entry level of 0.3%. All false data entries were corrected.
All analyses were performed using SPSS (release 11.5.1) statistical software. Missing items in the questionnaire were treated as follows. For the SAQ no advice is available on scoring missing items. If one item was missing, we regarded the dimension score (which the item was part of) as being missing completely, according to earlier research [25]. For the BIS no missing values were allowed since three questions were omitted already. In these cases, the entire score was omitted. For the three omitted questions, the individual mean score of the remaining seven questions was imputed.
First, we determined how many patients in both treatment groups were sexually active before and after treatment. An overall percentage per treatment group was calculated, after which sexual activity in subgroups was assessed: those being sexually active and those not being sexually active before treatment. Second, the mean of the dimension scores were plotted for the hysterectomy and UAE group. Third, the mean differences between all follow-up SAQ dimension scores and baseline were compared between treatment groups. This was only possible for patients who were sexually active both before and after treatment. Within group changes were analyzed as well. Similar analyses were performed for the BIS. Differences in pleasure, discomfort, habit (SAQ), and body image (BIS) between groups over time were tested with repeated measurement analysis, excluding the 6-week measurement for the SAQ, since a high proportion of patients was expected not to be sexually active at that time and therefore not to yield a score. Differences in continuous variables were tested with Student’s t test. Differences in data with skewed distributions were tested with the nonparametric Mann-Whitney U test.
The two added questions on the quality of current sexual life were compared between the groups using the chi-square test (or Fishers’ exact test when appropriate). Furthermore, the quality of sex life and the additional questions at the various follow-up moments were compared to baseline, yielding two different options: “worse,” “the same,” or “better” compared to baseline. Differences between the groups were compared with the chi-square test (or Fishers’ exact test when appropriate).
Logistic regression analysis was performed to investigate variables associated with a worse sexual life quality at 24 months after treatment compared to baseline versus unchanged or improved quality of sexual life. First, univariate analysis was performed with the following baseline characteristics: intended treatment, age, BMI, parity, ethnicity, having a partner, employment status, smoking status, number of fibroids, uterine volume measured by ultrasound, dominant fibroid volume measured by ultrasound, existence of any comorbid disease, and mental health status (MCS-MOS-SF36) at baseline. Second, covariates with p values <0.1 in the univariate analysis were selected for multivariate analysis.
All analyses were two-tailed and carried out based on the intention-to-treat principle. A p value <0.05 (two-tailed) was considered statistically significant.
Results
Patients were enrolled between March 2002 and February 2004. Of 349 eligible patients, 177 were randomized: 89 were allocated hysterectomy and 88 were allocated UAE. In the hysterectomy group 14 patients refused the allocated treatment, compared to 7 patients in the UAE group, and these patients withdrew from participation. In 4 UAE patients embolization failed bilaterally. These patients subsequently had a hysterectomy but were analyzed in the UAE group according to the intention-to-treat principle (Fig. 1) [15]. The baseline characteristics of all randomized patients are reported in Table 2. No differences between the groups are apparent, as expected considering the randomized design.
Fig. 1FlowchartTable 2Baseline characteristicsUAE (N = 88)Hysterectomy (N = 89)Age (yr), mean (SD)44.6 (4.8)45.4 (4.2)Body mass index (weight [kg]/length [m]2), mean (SD)26.7 (5.6)25.4 (4.0)Parity (n)  030 (34.1%)20 (22.5%)  ≥158 (65.9%)69 (77.5%)Ethnicity (n)  Black24 (27.3%)20 (22.5%)  White54 (61.4%)57 (64.0%)  Other10 (11.4%)12 (13.5%)Marital statusa (n)  Single16 (18.2%)13 (14.8%)  Married55 (62.5%)54 (61.4%)  Living apart together5 (5.7%)4 (4.5%)  Divorced12 (13.6%)15 (17.0%)  Widow0 (0%)2 (2.3%)Partner relationshipa (n)  No partner13 (15.3%)19 (22.4%)  Partner72 (84.7%)66 (77.6%)Employment statusa (n)  Employed68 (77.3%)69 (78.4%)  Unemployed20 (22.7%)19 (21.6%)Smoking status (n)  Current smoker21 (23.9%)23 (25.8%)  Former smoker11 (12.5%)14 (15.7%)  Nonsmoker56 (63.6%)52 (58.4%)Comorbid diseaseb  Any comorbid disease24 (27.3%)22 (24.7%)Number of fibroids, median (range)2 (1–20)2 (1–9)Uterine volume (cm3), median (range)321 (31–3005)313 (58–3617)Fibroid volume (dominant fibroid; cm3), median (range)59 (1–673)87 (4–1641)Mental Component Summary (SF-36), mean (SD)40.9 (10.7)41.5 (11.0)aSome values are missingbAny of the following: hypertension, diabetes, astma, clotting disease, system disease, or other
The proportion of questionnaires available for analysis ranged from 96.0% (baseline) to 98.7% (6 weeks, 24 months). Before treatment 54 of 81 (67%) and 46 of 75 (61%) of the participating patients were sexually active in the UAE and hysterectomy groups, respectively (Fig. 2A). Six weeks after treatment, sexual activity had decreased in both groups, with significantly more patients showing sexual activity in the UAE group compared to hysterectomy (53% versus 29%; p = 0.004). Hereafter sexual activity was restored in both groups, with no significant differences between the groups at 24 months (p = 0.07).
Fig. 2Proportion of sexually active women, by treatment strategy, over time. (A) The weighted average of women who were not sexually active at baseline (B) and those who were sexually active at baseline (C)
Patients who were not sexually active before treatment gradually resumed sexual activity after both UAE and hysterectomy (Fig. 2B). After 24 months 31% (hysterectomy) and 52% (UAE) were sexually active (p = 0.118). No significant differences were observed between the groups.
Among those patients who were sexually active before treatment, there was a major drop in activity at 6 weeks after treatment, which was partially restored. After 2 years, 86% (UAE) and 90% (hysterectomy) of these patients had resumed their sexual activities (Fig. 2C). Only at 6 weeks had significantly more UAE patients resumed sexual activity (p = 0.01).
Figure 3 shows the course of the SAQ dimensions pleasure, discomfort, and habit and the BIS scores over time. There were no differences between the groups at baseline (pleasure, p = 0.76; discomfort, p = 0.44; habit, p = 0.77; body image,: p = 0.60). Repeated measurements revealed no differences between the groups for the SAQ dimensions pleasure (p = 0.343), discomfort (p = 0.246), and habit (p = 0.453) or for body image scores (p = 0.359). Table 3 shows the changes in dimension scores per treatment group for patients who were sexually active at baseline. Positive numbers for pleasure and habit and negative numbers for discomfort and body image are indicative for improvement compared to baseline. No significant differences were found between the two treatment groups at all time points, except for body image at 6 months after treatment: body image had improved significantly more in UAE patients than in hysterectomy patients (UAE, –1.34, versus hysterectomy, no change; difference, –1.34; 95% CI, –2.50 to –0.18; p = 0.02). Within the groups, however, a significant improvement of various dimension scores was noted (indicated in boldface): at 24 months UAE patients reported significantly less discomfort, a higher frequency of intercourse, and a better body image compared to baseline (p = 0.022, p = 0.022, and p = 0.009 respectively). At 24 months hysterectomy patients improved on all dimensions compared to baseline, but differences were not statistically significant.
Fig. 3Pleasure, discomfort, habit, and body image, by treatment strategy, over timeTable 3Mean differences in pleasure, discomfort, habit, and body image compared to baseline, by treatment strategy, over timeUAEHysterectomyp valueSAQ: pleasure (0–18)a  6 wk0.29−0.500.47  6 mo1.631.230.61  12 mo0.951.490.50  18 mo1.860.680.13  24 mo0.891.180.74SAQ: discomfort (0–6)b  6 wk−0.25−0.210.96  6 mo−0.58−0.320.41  12 mo−0.47−0.470.98  18 mo−0.51−0.290.51  24 mo−0.43−0.490.88SAQ: habit (0–3)a  6 wk−0.030.000.92  6 mo0.480.280.30  12 mo0.180.420.24  18 mo0.270.190.70  24 mo0.280.220.74BIS (0–30)b  6 wk−1.27−0.280.10  6 mo−1.340.000.02  12 mo−0.240.080.64  18 mo−1.24–0.280.15  24 mo−1.06–0.500.36Note. SAQ, Sexual Activity Questionnaire; BIS, Body Image Scale. Boldface numbers indicate a significant difference from baseline within group (p < 0.05)aA higher score represents more favorable sexual functioning (pleasure, habit)bA lower score represents more favorable sexual functioning (discomfort) or body image
Table 4 reports the patients’ experienced quality of their sexual life at 6 weeks and 12 and 24 months. No differences between groups were observed. Table 5 presents the proportion of patients who judged the quality of sexual life as better, comparable to, or worse compared to baseline based on the question: “How is the quality of your current sexual life?” A minority of patients reported worsened sexual life quality compared to baseline at all time points. At 24 months the proportion of patients reporting a worse sexual life compared to baseline was slightly higher in the UAE than in the hysterectomy group, but the difference was not statistically significant (29.3% versus 23.5%; p = 0.43).
Table 4Satisfaction with sexual life and ability to cope with sexual life, by treatment strategy, over timeBaseline6 weeks12 months24 monthsUAE (N = 81)Hyst. (N = 75)p valueUAE (N = 81)Hyst. (N = 75)p valueUAE (N = 81)Hyst. (N = 75)p valueUAE (N = 81)Hyst. (N = 75)p valueHow is the quality of your current sex life?  Very good1580.84710.487110.358110.54  Good2227252231182921  Somewhat good15131213911812  Neither good nor bad1212231915211615  Somewhat bad66445388  Bad43583444  Very bad33214251How well can you live with your current sex life?  Very good930.771160.3318170.9320170.78  Good2021373035303431  Somewhat good1012151611131011  Neither good nor bad201710564106  Somewhat bad89251325  Bad44252222  Very bad65011100Table 5Changes in sexual wellbeing compared to baseline, by treatment strategy, over timeUAE (n = 81)Hysterectomy (n = 75)p value6 months  Worse16130.68  The same2527  Improved322512 months  Worse17140.81  The same2926  Improved252724 months  Worse22160.32  The same2720  Improved2632
Univariate logistic regression analysis revealed BMI, number of fibroids, and presence of comorbid disease to be associated with a worsened quality of sexual life at 24 months compared to baseline (p < 0.1). Allocated treatment and mental health at baseline were not associated with worse outcome.
BMI was not significant in the multivariate analysis (p = 0.163). The other two parameters remained significantly associated with worse outcome: a higher number of fibroids (OR, 0.69; 95% CI, 0.51–0.94; p = 0.018) predicted a decreased risk of a worsening sexual life at 24 months compared to baseline, while the presence of comorbid disease (OR, 3.20; 95% CI, 1.38–7.41; p = 0.007) was associated with an increased risk of a worse sexual life quality at 24 months after treatment compared to baseline.
Discussion
In our trial no differences, on average, in sexual function at 24 months were observed between UAE and hysterectomy. After both treatments the dimensions “pleasure” and “habit” improved, while the dimension “discomfort” decreased at 24 months compared to baseline, although only the UAE group showed significant improvement in discomfort and frequency of intercourse.
Sexuality and body image after UAE have never been evaluated in a randomized controlled trial before. However, some nonrandomized series have addressed this subject. The improvement of sexual functioning after UAE was in accordance with the limited number of earlier studies on this subject [26–28], which reported a significant improvement in sexual functioning as well. Sexual functioning after hysterectomy has received much attention in the literature. Improvement in sexual functioning after hysterectomy might indirectly be associated with the consequences of surgery, such as less worry about unwanted pregnancy, absence of vaginal bleeding, and more time for sexual activities by the cessation of monthly periods [29]. Most reports on sexual functioning after hysterectomy found significant benefits in various aspects of sexual functioning [25, 30–35]. In contrast, the improvement in sexual functioning within our hysterectomy group at 24 months of follow-up was not statistically significant in our trial. This might be explained by insufficient power, which is partly due to the relatively small sample size for the SAQ scores in our population: change scores were only available from women who were sexually active at baseline and at follow-up. Furthermore, the studies on sexuality after hysterectomy used varying follow-up intervals, ranging from 6 months to 2 years. In our series, hysterectomy patients experienced significantly improved pleasure and habit scores at 12 months of follow-up. These results might indicate that improvement in sexual functioning after hysterectomy could be temporary. On the other hand, a review article recently suggested that there is no scientific proof for either improvement or deterioration of sexual functioning after hysterectomy, unless hysterectomy was performed based on a sound clinical indication [29]. In our patient group, however, there was no doubt about the indication: complaints were serious and lengthy enough to warrant a hysterectomy.
Although, on average, SAQ scores for the group as a whole improved, there was a small group of women who reported a deterioration in self-reported quality of sexual life, consistent with other reports [30–32, 34, 36]. For obvious reasons, the prospects of deterioration of sexual life might be of greater concern to patients than the improvement after treatment. Regression analysis of worsened sexual life revealed that women with a low number of fibroids (possibly representing a group of women with less severe complaints) and women with other concomitant chronic diseases might not benefit from fibroid treatment in terms of sexual life improvement.
The improved body image after UAE in our series is in accordance with another study that reported higher self-consciousness after UAE [26]. After hysterectomy a period of temporary worsened body image following the operation has been described previously [25, 36, 37]. This was not confirmed by our results, but in accordance with these studies, a normal or even improved body image was found 1 year after hysterectomy.
There are several limitations of our study that need to be addressed. First, the values of the SAQ dimensions were based on all sexual active women at the various points in time. Reported values may reflect an ever-changing group of sexually active women. At any stage, some women may cease while others may initiate sexual activity. Of all non-sexually active women before treatment, 50% became active after treatment. When comparing pre- and posttreatment scores, these women cannot be included, since their baseline scores were missing.
Second, the significant difference between resumption of sexual activity between the groups at 6 weeks is probably explained by differences in counseling between both treatments as mentioned earlier: hysterectomy patients in our trial were told not to have sex until the first outpatient visit at 6 weeks, while UAE patients were advised to refrain from intercourse for at least 2 weeks and thereafter, depending on their complaints.
Third, we allowed all kinds of hysterectomies, thereby possibly biasing the results in the hysterectomy group. However, various reports found no long-term differences in sexual functioning after various surgical routes of hysterectomy [25, 32, 35].
Finally, as described above, three questions on the BIS were omitted because of wrongly posed questions, thereby creating asymmetry in the treatment arms. Since the remaining questions in both groups were identical, the comparison between the groups is still valid but reduces the comparability with other series.
In conclusion, at 24 months no differences in sexuality and body image were observed between the UAE and the hysterectomy groups. After both UAE and hysterectomy, on average, sexual functioning and body image scores improved, but significantly so only after UAE.

sexuality
body image
uterine artery embolization
hysterectomy
fibroid
leiomyoma


Normative data on the Bonn Risk Index for calcium oxalate crystallization in healthy children

Bonn Risk Index (BRI) is being used for the assessment of urinary calcium oxalate (CaOx) crystallization. There are no published data regarding BRI during growth. The objective of this study was to establish age- and sex-dependent BRI values in healthy children and adolescents. A total of 1,050 Caucasian subjects aged 3–18 years (525 males, 525 females) without a history of kidney stone disease were enrolled in the cross-sectional study. The study group was divided into 15 ranges according to age, each comprising 70 subjects. Urinary ionized calcium [Ca2+] was measured using a selective electrode while the onset of spontaneous crystallization was determined using a photometer and titrating with 40 mmol/L ammonium oxalate (Ox2−). The calculation of BRI value was based on the ratio of [Ca2+] to the required amount of ammonium oxalate added to 200 ml of urine to induce crystallization. The median BRI was 0.26 1/L and the values of the 5th and 95th percentiles were 0.06 1/L and 1.93 1/L, respectively. BRI correlated positively with body-area-related BRI (1/L × 1.73 m2) (R = 0.18; P < 0.05), whereas a negative correlation was found between BRI and body weight (1/L × kg) (R = −0.85; P < 0.05). Neither sex nor age differences were detected in BRI across studied children and adolescents. The values of Bonn Risk Index were constant during growth and there was a limited influence of age and sex on BRI in children over 3 years of age. The BRI may be valuable in the evaluation of pediatric patients at risk for kidney stones, particularly if the BRI from stone formers is demonstrated to be higher than in normal children.
Introduction
Urolithiasis is a frequently reported condition in children and is diagnosed even in neonates and infants [1, 2]. The disease may be the first sign of congenital and acquired metabolic disturbances, or the consequence of anatomic or genetic abnormalities [2]. The majority of kidney stones are composed of calcium oxalate and calcium phosphate [1]. Insight into this pathology is increasing and is focused on the pathogenesis of deposit formation in the urinary tract [3–5]. Investigation is being conducted into more effective methods which would enable the detection of risk factors for urolithiasis. One of the risk factors is an increase in the crystallization of calcium oxalate (CaOx) in urine. Kavanagh and Laube recently published a review of methods used to assess the crystallization of CaOx in urine [6]. During the last few years, activity products (AP) of crystallization have usually been assessed by means of the APCaOx index or as the relative supersaturation (RS) of urinary calcium oxalate (RSCaOx) using the computer program EQUIL [7, 8].
Laube et al. showed that the ratio of calcium ions [Ca2+] to the amount of ammonium oxalate added to 200 ml of urine to induce crystallization [designated here as (Ox2−)] may be, at the moment of spontaneous crystallization of CaOx, an indicator of the risk of CaOx crystal formation [9]. The authors made this determination with a direct urine collection, without an initial processing. This ratio is known as the Bonn Risk Index (BRI): BRI=[Ca2+]/(Ox2−) 1/L [9, 10]. Due to its characteristics, this index is an accurate indicator of the individual state of balance between the quantities of the most important promoters and inhibitors of the crystallization process within urine [9, 10]. Measuring BRI is simple, cost-effective, and the results are repeatable. In patients with calculi formation, CaOx assessed using BRI is significantly higher when compared to healthy subjects [9]. A lack of published studies concerning BRI in pediatric patients led us to conduct the study in children and adolescents. The purpose of this study was to define the BRI value in healthy subjects aged 3–18 years, in relation to age and sex.
Materials and methods
The study was performed on a group of 1,050 healthy Caucasian children and adolescents (group I) aged 3–18 years (mean ± SD: 10.51 ± 4.33), comprised of 525 boys and 525 girls. The study population was divided into 15 age groups, consisting of 70 children in each 1-year group (35 boys and 35 girls). The children reported no history of dietary restrictions. All participants met the criteria of the standard dietary energy and nutrient intakes recommended in Poland [11]. These children were free of infection at the time of the examination (serum C-reactive protein CRP <0.4 mg/dL, blood leukocyte count <10 × 109/L). Prior to inclusion, all participants were screened regarding serum levels of protein, albumin, calcium, phosphate, potassium, uric acid, creatinine and alkaline phosphatase as well as urine concentrations of citrate, oxalate, potassium, calcium and phosphate. Urinary dipstick testing (Bayer Diagnostics, Bridgend, UK) detecting nine parameters, including leukocytes, protein and blood, did not reveal any abnormalities. Children with a family history of kidney stones were excluded from the study. Subjects with diseases known to affect oxalate, calcium and phosphate metabolism and children treated with antibiotics were excluded. All children were screened using renal ultrasound examination to exclude urolithiasis (Toshiba SSH-140A apparatus; probe Convex 3.75 MHz). Participants and their legal guardians gave informed consent, and the study was approved by the Ethical Committee of the Medical University of Bialystok.
Bonn Risk Index
The Bonn Risk Index was assessed using the method of Laube [12]. Each child had a 24-h urine collection into sterile containers, without additional preserving substances, which was stored at 4°C. The testing was always performed twice using the same urine collection from each subject. Two consecutive urine samples (each 200 mL) were incubated immediately after collection, at a temperature of 37°C and the calcium ion concentration was measured using calcium ion-selective electrodes of type Rapilab 855 (Bayer, Germany) and titrated with ammonium oxalate solution (40 mmol/L) at a rate of 0.75 mL/min. The onset of spontaneous crystallization was detected using an Eppendorff photometer (filter 585 nm) with a decrease in light transmission to 98% of the initial value. Each analysis was repeated twice. The BRI is presented as [Ca2+] mmol/L /(Ox2−) mmol = 1/L. Calibration and quality assurance procedures, based on the calibration curves, were conducted every day.
Statistical analysis was performed using the program Statistica 6.0 PL. Mann-Whitney test was used for the analysis of two non-parametric independent variables, with P < 0.05 considered statistically significant. Assessment of the rank of two independent variables was conducted using Spearman correlation, with P < 0.05 considered statistically significant. For the purpose of plotting the curve of spontaneous crystallization (an association between the number of calcium ions and the amount of added ammonium oxalate leading to the spontaneous crystallization), we used the computer program with the range of values as a scatterplot with the option of adding curves.
Results
The characteristics of the study group are presented in Fig. 1. The anthropometric traits of participants, based on weight and height measurements and body mass index (BMI), were within the normal range in each subgroup, relative to the Polish references described by other authors [13].
Fig. 1Body mass index (BMI) in studied girls and boys aged 3–18 years compared to age and sex-matched reference range
Figure 2 shows the detailed results for the whole study group for BRI, defined as the ratio of [Ca2+] concentration in urine to the amount of added ammonium oxalate (Ox2−) necessary for the spontaneous crystallization of CaOx. BRI in healthy children ranged between 0.06 and 1.93 1/L. The values between the 5th and 95th percentiles are found between the two borderline arrows. This diagram also presents the minimum and maximum concentrations of [Ca2+] and the required amount of added oxalate (Ox2−). The concentration of [Ca2+] in urine ranged from 0.25 mmol/L (5th percentile) to 0.89 mmol/L (95th percentile) with a median of 0.42 mmol/L, and an amount of added (Ox2−) ranging from 0.46 mmol (5th percentile) to 3.53 mmol (95th percentile) with a median of 1.65 mmol.
Fig. 2The spontaneous crystallization of CaOx in urine of 1,050 children aged 3.00–17.99 years. The x-axis shows amount of ammonium oxalate (Ox2−) in mmol necessary for the onset of spontaneous crystallization. The y-axis shows the concentration of calcium ions [Ca2+] before adding Ox2−. The extremes of the hyperbola represent minimum and maximum values. The minimum hyperbola is defined by the equation [Ca2+]=0.27/(Ox2−), and the maximum is [Ca2+]=1.67/(Ox2−). The BRI values for the 5th to the 95th percentile are found between the hyperbolas [Ca2+]=0.39/(Ox2−) and [Ca2+]=0.94/(Ox2−), median [Ca2+]=0.65/(Ox2−)
Figure 3 presents the BRI values in children representing various age groups. We considering the subjects in two main subgroups, younger children aged 3–9 years, and older children and adolescents aged 10–18 years. In children 3–9 years of age, the lowest values of BRI were found in the youngest children, i.e. those 3 years old (median 0.18 1/L), whilst the highest values were found in 9-year-old children (median 0.34 1/L). However, statistical analyses did not show a difference between the values across the various age groups. The lowest median BRI value was 0.03 1/L in 9-year old children, whilst the highest median value was 2.48 1/L in 4-year-old children. The BRI values for younger children corresponding to the 5th percentile ranged from 0.03–0.08 1/L, and the 95th percentile from 1.38–2.27 1/L.
Fig. 3Bonn Risk Index (BRI) in the whole studied group (left box) and in separate 1-year age groups for children aged 3–18 years
In older children and adolescents aged 10–18 years, the lowest BRI values were found in the participants who were 12 years old (median 0.17 1/L), whilst the highest were in 17-year-old adolescents (median 0.31 1/L) (Fig. 3). However, statistical analysis did not show significant differences between the age subgroups. The minimum value of BRI was 0.02 1/L, and was found in 11-year-old children, whereas the maximum value was 3.1 1/L in children aged 10 and 17 years. The BRI values for older children corresponding to the 5th percentile ranged between 0.05 and 0.13 1/L, whilst the 95th percentile was from 1.69–2.66 1/L.
The crystallization values of CaOx, based on BRI in healthy children aged 3–18, did not exceed 2.66 1/L. No significant differences were found in the BRI values between boys and girls in either age group.
Table 1 presents the BRI and BRI related to the 1.73 m2 body surface area and body mass (kg). The median BRI in relation to body surface area (1/L × 1.73 m2) was 0.39 1/L × 1.73 m2, with 5th and 95th percentile medians of 0.09 and 3.01 1/L × 1.73 m2, respectively. However, the median BRI in relation to 1 kg of weight was 0.008 1/L × kg with corresponding 5th and 95th percentiles of 0.0015 and 0.06 1/L × kg, respectively. A weak positive correlation was found between BRI and BRI/1.73 m2 (R = 0.18, P < 0.05), and a negative correlation was found between BRI/1.73 m2 and BRI/kg (R = −0.86, P < 0.05). No differences were found between the values of BRI/1.73 m2 and BRI/kg in the various age groups or in relation to sex.
Table 1Bonn Risk Index values in children aged 3–18 years in relation to body surface area and body weight MedianMinimumMaximum5th percentile95th percentileBRI (1/L)0.260.023.100.061.93BRI/1.73 m2(1/L × 1.73 m2)0.390.036.650.093.01BRI/kg (1/L × kg)0.0080.00060.150.00150.06
Discussion
Urinary stones are considered a major health problem in society, both in adults and in children, due to their recurrent nature and the cost of treatment [14]. The pathogenic pathways leading to stone formation in kidneys have not been fully explained. During processes of calculus formation, a number of phenomena have been reported such as excess of crystallizing substances, nucleation, crystallization, aggregation and stone formation [15, 16]. However, it has not been explained why calculi do not form in all subjects, despite a large amount of urinary crystallization products. Over the past few years, there have been many attempts to define the risk factors leading to urinary stone formation on the basis of the ability to form oxalate crystals, a main component of calculi [7, 8, 17]. Tiselius et al. described the practical importance of assessing the activity of calcium oxalate ions in urine using the APCaOx index [7].
Stone formation has also been evaluated in terms of excess urinary calcium oxalate, using the computer program EQUIL [18, 19]. Laube et al. showed a strong correlation between the concentration of free calcium ions [Ca2+] in urine and the quantity of ammonium oxalate (Ox2−) added to invoke spontaneous urinary crystallization of CaOx [9]. The authors suggested that the BRI index in healthy subjects was significantly lower than in those forming urinary calculi. The study, based on a group of 72 healthy subjects, provided mean BRI values of 1.05 ± 1.038 1/L with a range of 0.06–4.89 1/L. In other studies involving 85 healthy adult subjects, the mean BRI values were similar, 0.89 ± 0.91 1/L. Higher BRI values have been described by Lewandowski et al. whose study group of 15 Caucasian adults demonstrated a mean BRI of 4.90 1/L, and 15 African adults had a mean BRI of 2.04 1/L [10]. The literature review did not reveal any larger or more comprehensive studies regarding BRI in children.
Our findings in the large group of healthy children showed that the normal BRI value ranged from 0.06 1/L (5th percentile) to 1.93 1/L (95th percentile). The maximum values obtained in children were lower than those described by other authors in adult populations [6, 9, 20]. This may be due to the fact that the mechanism which inhibits crystal formation in children’s urine is more effective when compared to adults. Teller et al. observed that urinary glycosaminoglycans in children reduced the aggregation of crystals more effectively than in adults [21]. A similar age-related effect regarding stone formation has been observed by Bergsland et al., who showed that the urine of subjects aged less than 20 years produced a strong inhibitory effect on crystal formation [22]. Ricchiuti et al. investigated the process in boys aged less than 10 years and found increased activity of plasma protease inhibitor (inter-alpha inhibitor), blocking urinary crystallization during various stages [23].
Our results did not show a significant difference in BRI values between boys and girls. A minor difference was found in relation to age, but this was not significant. The BRI/1.73 m2 and BRI/kg behaved similarly. High correlations between BRI, BRI and body weight, and BRI and body surface area of studied subjects enable practical, more objective use of BRI and allow for comparisons between individuals. For this reason, these results are presented as median values with ranges for the 5th to 95th percentiles for the whole study group.
The study has several limitations. So far, the use of our normative data appears to be limited to the Polish population. It is difficult to relate the results to other geographical regions or to different ethnic groups as there are no published data regarding BRI in children. Further comparative and prospective investigations are needed because a cross-sectional study is not able to reveal whether some children with a normal BRI value will be at risk for stone disease in the future. Moreover, some studied children may have had urolithiasis despite normal results of renal ultrasound. However, this study provided consistent normative data on BRI, due to both the large age representation and the stringent selection criteria.
In summary, the Bonn Risk Index, expressed as the ratio of ionized calcium to the amount of ammonium oxalate necessary to initiate spontaneous CaOx urinary crystal formation, is lower in healthy children and adolescents aged 3–18 years than in studies of adults by other authors. The BRI during growth appears to be independent of age and sex. Thus, our results may contribute to the effective screening of kidney stone disease in pediatric subjects. We conclude that the BRI may be valuable in the evaluation of pediatric patients at risk for kidney stones, particularly if the BRI from stone formers is demonstrated to be higher than in normal children.

oxalate crystallization
children
bonn risk index (bri)
normative values


Clinical review: Complications and risk factors of peripheral arterial catheters used for haemodynamic monitoring in anaesthesia and intensive care medicine

In order to evaluate the complications and risk factors associated with peripheral arterial catheters used for haemodynamic monitoring, we reviewed the literature published from 1978 to 2001. We closely examined the three most commonly used arterial cannulation sites. The reviewed papers included a total of 19,617 radial, 3899 femoral and 1989 axillary artery catheterizations. Factors that contribute to higher complication rates were investigated. Major complications occurred in fewer than 1% of the cases, and rates were similar for the radial, femoral and axillary arteries. We conclude that arterial cannulation is a safe procedure.
Introduction
Indwelling arterial catheters are used routinely for continuous haemodynamic monitoring in the operating room during major surgery and in critically ill patients. Arterial cannulation provides easy and convenient access, allowing multiple blood samplings and blood gas analysis. Arterial cannulation has generally been found to be a safe procedure, with few serious complications [1,2,3,4,5,6]. Approximately 8 million and 2.5 million arterial catheters are placed yearly in the USA and Europe, respectively [7]. Despite the frequency with which arterial catheters are employed, there is little information on the impact of cannulation site on risk for complications [8]. We reviewed reports concerning arterial cannulation sites such as the radial, femoral, axillary, brachial, ulnar, dorsal pedis, tibial posterior and temporal arteries with regard to thrombotic, infectious and vascular complications.
Material and methods
The PubMed, Medline Express and Winspirs databases (publication years 1978-2001) were searched to identify pertinent articles. The keywords 'artery catheter', 'radial artery catheter', 'femoral artery catheter', 'axillary artery catheter', 'catheter complication', 'hemodynamic monitoring' and 'peripheral methods' were used. We reviewed the papers and identified further articles from the references of the papers found in the initial search.
We reviewed all studies concerning the use of radial, femoral, axillary, brachial, ulnar, dorsal pedis, tibial posterior and temporal artery catheters for haemodynamic monitoring that dealt with complications and risk factors in adults. We excluded studies conducted in the paediatric patient population.
We opted not to perform statistical analyses because the data selection of the published reports do not follow the same criteria, and most of them give no specific information regarding patient population, catheter material, cannulation technique and times. Therefore, comparison between studies and statistical analyses are unlikely to be valid.
Results
We identified 78 studies that met our criteria.
Radial artery
The radial artery is the most common site for arterial cannulation, and the studies that reported complication rates are listed in Table 1 [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]. The most common complication was temporary occlusion of the artery, the incidence of which ranged from 1.5% [17] to 35% [10] (mean 19.7%), the variability being due to the different methods employed and the degree of effort invested in detecting this complication.
Table 1
Complications following radial artery cannulation
Reference
Cases
Permanent ischaemic damage (n)
Temporary occlusion (n)
Sepsis (n)
Local infection (n)
Pseudoaneurysm (n)
Haematoma (n)
Bleeding (n)
[9]*
80
1
9
0
0
-
-
-
[9]*
34
1
10
0
2
-
-
-
[10]
100
0
35
-
-
-
-
-
[11]
148
0
27
-
-
-
-
-
[12]
29
0
5
-
-
-
-
-
[13]
62
0
16
0
0
-
-
-
[14]
333
0
100
0
16
-
29
-
[15]
40
0
2
-
-
-
-
-
[16]
100
2
14
0
1
-
31
-
[17]
197
0
3
3
4
2
-
1
[18]
178
0
7
1
3
-
-
1
[5]
1699
0
360
0
1
-
206
-
[19]
26
0
6
0
1
1
1
-
[20]
100
0
14
-
-
-
-
-
[21]
100
0
33
0
1
-
13
-
[22]
118
0
18
0
0
-
21
-
[23]
200
0
15
-
-
-
61
-
[24]
25
0
3
0
0
-
-
-
[25]
200
0
60
0
0
-
32
-
[26]
193
0
50
0
4
-
-
-
[27]
88
0
15
-
-
-
-
-
[28]
2900
-
-
4
12
5
-
-
[29]
38
0
3
-
-
-
5
-
[30]*
45
0
4
-
-
-
10
-
[30]*
44
0
11
-
-
-
9
-
[31]
12,500
-
-
-
-
6
-
-
[32]
40
0
11
-
-
-
-
-
Mean incidence (%)
0.09 (4/4217)
19.7 (831/4217)
0.13 (8/6245)
0.72 (45/6245)
0.09 (14/15,623)
14.40 (418/2903)
0.53 (2/375)
The total number of cannulations was 19,617. *One study examining two different populations. -, Not investigated.
Generally, temporary occlusion of the artery has no serious sequelae. Permanent occlusion of the radial artery appears to be rare because it was reported in only four patients (mean incidence 0.09%).
Another serious complication is pseudoaneurysm, which was reported in 14 patients (mean incidence 0.09%). Pseudoaneurysm poses a risk for infection, sepsis, rupture [33,34,35] and formation of an extracorporeal pseudoaneurysm [36]. Radial catheterization was associated with sepsis in eight patients (mean incidence 0.13%), whereas local infection at the cannulation site was identified in 45 patients (mean incidence 0.72%).
Minor complications such as haematoma formation or bleeding at the puncture site are also shown in Table 1. Other complications include abscess, cellulitis, paralysis of the median nerve [37,38,39], suppurative thrombarteritis [40], air embolism [41], compartment syndrome and carpal tunnel syndrome [42,43,44]. Other rarely reported complications include catheter failure as result of manufacturing defect or incorrect use with resultant catheter replacement [45,46,47,48].
Femoral artery
We identified 11 studies that used the femoral artery for haemodynamic monitoring, which are listed in Table 2 [17,18,19,49,50,51,52,53,54,55,56]. Temporary occlusion was reported in 10 patients (mean incidence 1.45%), and serious ischaemic complications requiring extremity amputation was reported in three patients (mean incidence 0.18%) [56].
Table 2
Complications following femoral artery cannulation
Reference
Cases
Permanent ischaemic damage (n)
Temporary occlusion (n)
Sepsis (n)
Local infection (n)
Pseudoaneurysm (n)
Haematoma (n)
Bleeding (n)
[49]
46
-
-
0
-
-
-
-
[50]
50
0
1
0
-
-
5
-
[51]
85
0
0
0
-
-
10
-
[17]
113
0
0
0
0
-
-
4
[52]
89
-
-
0
0
-
-
1
[53]
2100
-
-
6
-
6
-
-
[18]
114
0
4
2
0
-
-
0
[54]
42
0
1
0
1
-
3
-
[55]
220
0
1
4
4
-
8
-
[19]
64
0
3
1
0
-
2
-
[56]
976
3
-
-
-
-
-
-
Mean incidence (%)
0.18 (3/1664)
1.45 (10/688)
0.44 (13/2923)
0.78 (5/642)
0.3 (6/2100)
6.1 (28/461)
1.58 (5/316)
The total number of cannulations was 3899. -, Not investigated.
Pseudoaneurysm formation occurred in six patients (mean incidence 0.3%), sepsis was observed in 13 patients (mean incidence 0.44%) and local infection was reported in five patients (mean incidence 0.78%). Bleeding (generally minor) was observed in five patients (mean incidence 1.58%), and haematoma formation was reported in 28 (mean incidence 6.1%). One patient developed an infected haematoma and needed blood transfusion [17] and another patient eventually died from massive retroperitoneal bleeding [57].
Axillary artery
The axillary artery was cannulated in a total of 1989 reported cases. The complication rates at this site are summarized in Table 3 [54,55,58,59,60,61]. Serious complications included permanent ischaemic damage in two patients (mean incidence 0.20%), pseudoaneurysm formation in one patient (mean incidence 0.1%) and sepsis in five patients (mean incidence 0.51%). Paresthesia of the hand due to pressure on the brachial nerve plexus was also described [54,59].
Table 3
Complications following axillary artery cannulation
Reference
Cases
Permanent ischaemic damage (n)
Temporary occlusion (n)
Sepsis (n)
Local infection (n)
Pseudoaneurysm (n)
Haematoma (n)
Bleeding (n)
[58]*
1000
-
-
-
-
1
-
-
[58]*
245
0
1
0
-
-
-
6
[59]
120
0
1
0
3
-
4
-
[60]
435
2
9
3
7
-
4
3
[54]
28
0
-
0
1
-
3
-
[61]
31
0
-
0
-
-
1
1
[55]
130
0
0
2
5
-
5
-
Mean incidence (%)
0.20 (2/989)
1.18 (11/930)
0.51 (5/989)
2.24 (16/713)
0.1 (1/1000)
2.28 (17/744)
1.41 (10/711)
The total number of cannulations was 1989. * One study examining two different populations. -, Not investigated.
Other sites for arterial cannulation
Other less frequently reported cannulation sites are the brachial, dorsal pedis, ulnar, tibial posterior and temporal arteries.
Only one serious complication was found in a study of 1000 patients [62] in which the brachial artery was used for invasive monitoring in ambulatory patients. This complication was an infected haematoma arising from a pseudoaneurysm. Another study that employed the brachial artery for arterial blood sampling in 6185 patients [63] also showed a small number of complications (incidence 0.2%), mainly paresthesias.
The dorsal pedis artery has also been cannulated without any major complications [24,54]. However, because of its distance from the central circulation and associated difficulties in hypotensive patients it is generally avoided [64]. The ulnar artery has been used without serious complications, and in a direct comparison [29] this site exhibited similar complication rates to those encountered with the radial artery.
The tibial posterior artery has been used in paediatric patients, without major complications [65,66]. However, there also exists a case report of limb amputation secondary to a tibial artery catheterization [67]. The temporal artery is an end artery of the external carotid artery, and is usually avoided for fear of serious complications. There is a report of three cases of cerebral embolization in paediatric patients [68].
Further studies
Other studies that examined arterial catheter complications but that did not specifically attribute their occurrence to one specific site are listed in Table 4 [49,69,70,71]. One study [69] used mainly the radial (n = 210), ulnar (n = 158) and dorsalis pedis arteries (n = 82), whereas another [49] used mainly the femoral (n = 46), brachial (n = 9), axillary (n = 3) and radial arteries (n = 1). One serious complication was found at the femoral site, with compromised circulation to the leg [70]; eventually, thrombectomy was required. Another reported serious complication is air embolism caused by improper use of the flushing device [70].
Table 4
Studies examining arterial catheter complications without specifically attributing them to any specific site
Reference
Cases
Air embolism (%)
Permanent occlusion (%)
Temporary occlusion (%)
Haematoma (%)
Bleeding (%)
Sepsis (%)
Abscess (%)
[69]
450
0
0
18.4
-
8.7
0
-
[49]
59
0
1.7
6.8
5.1
1.7
0
-
[70]
506
0.2
0
-
-
0
0
-
[71]*
1556
0
0
3.4
0.2
1.5
0.06
0.3
[71]�
565
0
0
4.6
0.3
2.3
0
0.5
*Medical intensive care unit (radial artery 52%, femoral artery 45%). �Surgical intensive care unit (radial artery 78%, femoral artery 11%). -, Not investigated.
A recent study [71] examined complication rates, comparing medical with surgical intensive care units. It also directly compared radial and femoral artery catheters. There were no significant differences in terms of sepsis and local infection rates between the femoral and radial arteries, and no significant difference between the medical and surgical intensive care units.
Another nine studies specifically looked for septic complications associated with arterial catheter placement, and included a total number of 1681 patients (Table 5) [52,54,72,73,74,75,76,77,78]. No septic complications were identified in seven of those studies [52,72,73,74,75,76,77], and nine cases of sepsis were reported in the remaining two studies [54,78]. All of the cases of sepsis were identified after the line had been in place for longer than 4 days. The studies in which sepsis was reported predominately used the radial artery.
Table 5
Incidence of sepsis following arterial cannulation
Reference
Cases
Sepsis (%)
[54]
130
4
[72]
172
0
[52]
186
0
[73]
19
0
[74]
155
0
[75]
643
0
[76]
230
0
[77]
75
0
[78]
71
5.5
Risk factors
A further objective of the present review was to consider risk factors that might have impacted on complication rates.
Thrombotic complications
Thrombus formation and occlusion of the artery appear to be caused by changes in the integrity of the vessel wall induced by the presence of the catheter [79]. Recannulation of the occluded artery generally occurs, but this may take up to 75 days [80]. The incidence of thrombus appears to be related to the degree to which the catheter fills the arterial lumen [3]. It has been shown that the incidence of radial obstruction increases linearly with the ratio of outer diameter to vessel lumen diameter [81]. This might explain the higher incidence of radial occlusion in female patients, who generally have vessels of smaller diameter [5,10,14,22,25]. This has led to a preference for 20-gauge catheters for radial artery cannulation [11,14]. Teflon catheters also appear to be associated with a lower incidence of occlusion [11], but in another study [5] this could not be confirmed. Patients with a low cardiac output have a higher incidence of radial artery occlusion [5,14], but no difference was found among patients with episodes of hypotension [21]. Multiple punctures for catheter insertion was shown to be a risk factor for complications in one study [14], but this could not be confirmed in another [5]. A higher incidence of occlusion is found in the presence of a haematoma [5,14,21]. Patients who are treated with aspirin or low-dose heparin have fewer vessel occlusions [13,14]. The age of adult patients does not appear to be a risk factor [14]. An important factor with regard to arterial occlusion is the duration of cannulation. A higher incidence of occlusion was reported when the cannula was left in place longer than 48 or 72 hours [5,9,14,16,25].
Infectious complications
Important factors in decreasing the incidence of catheter-related infections are aseptic insertion technique and adequate disinfection of the insertion site [82]. The risk for infectious complications and sepsis increases with the duration of cannulation, especially if the catheter is left in place for longer than 96 hours [78,83]. The catheter material also appears to be of importance, because Teflon has a greater resistance to Escherichia coli and Pseudomonas aeruginosa [84] and a lower affinity for stapylococci [85]. Prophylactic treatment with antibiotics does not appear to reduce the risk for catheter-related infections [78,83], but antibiotic bonding of the catheter may confer a degree of protection [86,87]. Arterial catheter placement via the cut-down technique is associated with a higher risk for infection [83]. Furthermore, sepsis occurs more frequently in the presence of local site inflammation [83]. Infection may also occur through contamination by caregivers of the monitoring system, the flushing device and the infusion system [88,89,90].
Discussion
The use of peripheral arterial catheters for haemodynamic monitoring is widespread. The most frequently used site is the radial artery because of its well documented low complication rates and easy access [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]. In the present review we report on 19,617 radial artery cannulations, and the main complication was temporary occlusion of the artery (incidence 19.70%). This complication rate is close to the finding of Wilkins [91], who reviewed reports of catheterization of the radial artery with regard to ischaemic complications published between 1969 and1983. He reported a temporary occlusion rate of 23%. In an extensive study of 1699 patients, Slogoff and coworkers [5] reported a 21.2% rate of temporary occlusion. Although temporary occlusion is reported quite frequently, serious ischaemic damage was reported in only two studies [9,16], with a mean complication rate of 0.09%. Nevertheless, there have been reports of serious ischaemic damage after radial artery cannulation that led to necrosis, and amputation of fingers or the whole hand [92,93,94,95,96,97,98,99].
Other major complications such as pseudoaneurysm and sepsis were reported to occur in a mean of 0.09% and 0.13% of cases, respectively.
The second most cannulated artery for haemodynamic monitoring is the femoral artery, and we reviewed 3899 cases. Temporary occlusion was reported in only 1.18% of the reviewed cases. The incidence of this complication in the femoral artery is much lower than that in the radial artery. We attributed this to the larger vessel diameter of the femoral artery. Serious ischaemic complications were reported in only one study [56], and the mean complication rate was 0.18%. The incidence rates for other major complications such as pseudoaneurysm and sepsis (0.3% and 0.44%, respectively) were similar to our findings in the radial artery. Some authors caution against use of the femoral artery for cannulation for fear of higher sepsis rates because of the close proximity to the perianal region [52]. We are unable to corroborate this on the basis of the reviewed literature, and recent studies that directly compared the radial and femoral arteries with regard to septic complications identified similar rates of sepsis [53,71]. In particular, in an extensive study of 4932 patients, Frezza and Mezghebe [71] were unable to identify a difference in complication rates between the radial and femoral arteries. In that study the femoral artery was actually the preferred site in the medical intensive care unit. Other authors prefer the femoral artery over the radial artery because the femoral artery is usually palpable even in hypotensive patients and may be the only accessible route for haemodynamic monitoring [64,100,101,102,103]. The blood pressure curve that is obtained from this larger artery is generally more accurate and gives a closer estimation of the aortic blood pressure [64,100,101,102,103].
The third most cannulated artery in the present review of the literature was the axillary artery, with almost 2000 reported cases. Some authors prefer not to cannulate the axillary artery because of its close location to the carotid artery and because of fear of embolism to the brain [101]. On the basis of the data summarized here we cannot confirm this, and no case of embolism to the brain was reported. Sometimes the axillary artery is avoided because of the more difficult approach required, although (particularly in anaesthesia) it is a well known route because it requires the same approach as that for axillary nerve block [3]. The major complications encountered with the axillary artery were similar to those for the radial and femoral arteries, and we conclude that it is a safe route for arterial cannulation.
Other reviewed arteries employed for catheterization, such as the brachial, dorsal pedis, ulnar, tibial and temporal arteries, have been used without serious complications, but published reports of their use are limited.
Conclusion
Incidence rates for major complications such as permanent ischaemic damage, sepsis and pseudoaneurysm formation are low and similar for the radial, femoral and axillary arteries. They occur in fewer than 1% of cases.
On the basis of the present systematic review we can conclude that serious complications of the radial, femoral and axillary artery are rare, and that arterial cannulation is a relatively safe procedure. Nevertheless, one must be aware of the possible serious complications that might arise. Therefore, it is important to use an arterial catheter only when it is indicated and to select carefully the best cannulation site individually for each patient, because the different cannulation sites have their specific advantages and attendant risks.
Competing interests
UJP is President of Pulsion Medical Systems AG, and AP is on the medical advisory board of Pulsion Medical Systems AG, whose PiCCO product uses a femoral arterial line.

complication
peripheral
catheter
haemodynamic monitoring
axillary artery
radial artery
femoral artery


Management of Massive Arterial Hemorrhage After Pancreatobiliary Surgery: Does Embolotherapy Contribute to Successful Outcome?

Massive arterial hemorrhage is, although unusual, a life-threatening complication of major pancreatobiliary surgery. Records of 351 patients who underwent major surgery for malignant pancreatobiliary disease were reviewed in this series. Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was achieved in five patients and one patient, respectively. However, 7 of 13 cases ended in fatality, which is a 54% mortality rate. Among six survivors, one underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA). Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic inflow was maintained by successful TAE of the gastroduodenal artery in two and via a well-developed subphrenic artery in one. One patient had TAE of the celiac axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was maintained by the arcades around the pancreatic head. One patient who experienced a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re-laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In contrast, four of seven patients with fatal outcomes experienced hepatic infarction following TAE proximal to the PHA or injury of the common hepatic artery during angiography. One patient who underwent a major hepatectomy for hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal artery and experienced hepatic failure. In the two patients with a pseudoaneurysm of the SPA or the superior mesenteric artery, an emergency re-laparotomy was required to obtain hemostasis because of worsening clinical status. Selective TAE distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be restricted to cases where collateral hepatic blood flow exists. Otherwise or for a pseudoaneurysm of the superior mesenteric artery, endovascular stenting, temporary creation of an ileocolic arterioportal shunt, or vascular reconstruction by re-laparotomy is an alternative.
Recent advances in surgical technique and postoperative management of major pancreatobiliary surgery have reduced the morbidity and mortality. However, the problem of life-threatening postoperative arterial hemorrhage caused by pseudoaneurysm rupture, although uncommon, has received little attention.1–6 Immediate arteriography to identify the site of bleeding and subsequent treatment by radiological intervention have been the first approach for the last decade.7–9 The efficacy of transcatheter arterial embolization (TAE) is well established.8–18 Nevertheless, occlusion by TAE sometimes causes distal end-organ damage, even though bleeding has been controlled.9–11 Indeed, complete interruption of hepatic inflow may lead to fatal hepatic necrosis, but risk factors for whole liver infarction have yet to be identified. Knowledge of which sites are associated with a high risk of hepatic necrosis would enable surgeons to choose an alternative to TAE, such as vascular reconstruction. Recent reports have documented an advantage of endovascular stenting over TAE.19–22 We reviewed the records of patients who experienced massive arterial hemorrhage after pancreatobiliary surgery to help generate guidelines for the management of postoperative pseudoaneurysm rupture.
Patients and Methods
From January 1993 to December 2005, 351 patients underwent major surgery for malignant pancreatobiliary disease in the Department of Gastroenterological Surgery, Yokohama City University. The cases were pancreatic cancer (n = 139), distal bile duct cancer (n = 58), ampullary cancer (n = 46), hilar bile duct cancer (n = 47), advanced gallbladder cancer (n = 42), and intrahepatic cholangiocarcinoma (n = 19). Procedures included pylorus-preserving pancreatoduodenectomy (PPPD) in 113, conventional pancreatoduodenectomy (PD) in 84, distal pancreatectomy (DP) in 35, segmental resection of the pancreas in 4, total pancreatectomy in 6, bile duct resection with partial hepatectomy in 98, and PD combined with partial hepatectomy (HPD) in 11. Patients undergoing isolated bile duct resection or partial hepatectomy without bile duct resection were excluded. Except for the patients who underwent DP, all patients received biliary tract reconstruction and skeletonization of the hepatic arteries to complete lymphadenectomy within the hepatoduodenal ligament. Pancreatojejunostomy was created as an end-to-side, duct-to-mucosa anastomosis with a stenting tube, or via the pancreatic duct insertion technique with total tube drainage when the pancreatic duct was smaller than 3 mm. Hepaticojejunostomy was created end-to-side in a single layer.
Massive postoperative arterial hemorrhage was defined as bleeding requiring a transfusion of 2 or more units of packed red blood cells, an invasive intervention such as laparotomy or TAE and monitoring in the surgical intensive care unit within 24 h of the onset of hemorrhage. The medical records of these patients were analyzed retrospectively.
Results
Of the 351 patients who underwent a major procedure, 13 (3.7%) presented with massive postoperative arterial hemorrhage (10 men and 3 women; average age, 66 ± 10 years). The demographic and clinical characteristics are summarized in Table 1.
Table 1Baseline Characteristics of PatientsCaseDiseaseOrigin of bleedSurgeryInterval (days)aSite of TAERe-laparotomyCause of bleedOutcome1Ampullary cancerRHAPPPD10RHANoPancreatic leakAlive2Gallbladder cancer RHA and RHAHPD8 and 12RHA and PHANoMinor injuryHepatic failure died3Hilar bile duct cancerRHAExtended left hepatectomy9NoneNoUnsuccessful reconstructionCancer recurrence, died4Gallbladder cancerGDAHPD10GDANoPancreatic leakAlive5Distal bile duct cancerGDAPD11GDAYesMinor injuryAlive6Distal bile duct cancerCHAPPPD24CHANoPancreatic leakAlive7Distal bile duct cancerPHAPD7NoneNoPancreatic leakSepsis, died8Hilar bile duct cancerGDARight hepatectomy7CHAYesMinor injuryHepatic failure died9Gallbladder cancerMHA and GDARight hepatectomy13 and 27MHA and CHANoPancreatic leakHepatic failure died10Gallbladder cancerGDARight hepatectomy7GDAYesPancreatic leakHepatic failure died11Pancreatic cancerSPADP17CAYesPancreatic leakAlive12Intrahepatic cholangiocarcinomaSPAHPD9NoneYesMinor injuryHepatic failure died13Pancreatic cancerSMAPPPD34NoneYesPancreatic leakMOF, diedTAE Transcatheter arterial embolization, RHA right hepatic artery, PHA proper hepatic artery, GDA gastroduodenal artery, CHA common hepatic artery, MHA middle hepatic artery, SPA splenic artery, CA celiac axis, SMA superior mesenteric artery, PPPD pylorus preserving pancreatoduodenectomy, HPD pancreatoduodenectomy combined with partial hepatectomy, DP distal pancreatectomy, PD pancreatoduodenectomy, MOF multiple organ failureaDays from surgery to hemorrhage
After restoration of hemodynamic stability by volume loading, 10 of 13 patients underwent emergency pan-abdominal angiography visualizing the celiac axis (CA) and superior mesenteric artery (SMA) by standard Seldinger technique. The other three patients required emergency laparotomy without angiography because their clinical status was deteriorating.
Of the 10 patients who underwent angiography, an arterial pseudoaneurysm was detected in 7: right hepatic artery (RHA) in two, gastroduodenal artery (GDA) in three, common hepatic artery (CHA) in one, and splenic artery (SPA) in one. Three patients had extravasation in the area of the middle hepatic artery (MHA), proper hepatic artery (PHA), or GDA without a clear source of bleeding (see Table 1).
TAE was attempted in nine patients using various coil occlusion devices. Table 1 details the origin of bleeding and the sites of TAE. Complete hemostasis was achieved by TAE in five patients, but hemostasis was only temporary in four: two required a second TAE and two required laparotomy to control rebleeding.
Of the three patients with a pseudoaneurysm distal to the PHA, one received selective TAE of the RHA with a successful outcome (patient 1). A second patient had recurrent hemorrhage after TAE of the RHA and second TAE of the PHA was required. Unfortunately, the cluster of coils compressed the portal vein and portal flow was disrupted after the second TAE. This patient died of hepatic failure secondary to hepatic hypoperfusion (patient 2). The third patient had undergone extended left hepatectomy with resection of the RHA and had bleeding from the site of the RHA reconstruction (patient 3). If TAE had been performed at the RHA, inflow to the small remnant liver would be completely interrupted, and fatal hepatic failure would have been the most likely outcome. Instead, we re-operated, ligated the RHA, and created an ileocolic arterioportal shunt to supply the hepatic remnant. The patient survived without hepatic failure. However, portal hypertension developed because this shunt remained patent 6 months after reoperation, and the patient died of spinal metastasis 11 months after the initial operation.
In seven patients, the pseudoaneurysm was proximal to the PHA and involved the GDA or CHA. Two patients successfully underwent selective TAE of the GDA for a pseudoaneurysm that originated from the ligated GDA. One patient had a replaced RHA from the CA, which contributed to a favorable outcome (patient 4, Fig. 1). One patient underwent TAE of the CHA uneventfully because the hepatic inflow was narrowly maintained by the left subphrenic artery (patient 6, Fig. 2). In contrast, the patient who had extravasation of the PHA without a discrete source had intimal injury and occlusion of the CHA during angiography. The patient experienced a liver abscess that was difficult to treat and died of sepsis and cancer recurrence during a long hospital stay (patient 7). Of the three patients who underwent right hepatectomy, two had complete disruption of the inflow to the hepatic remnant by TAE of the CHA, leading to fatal hepatic failure (patients 8 and 9), and one underwent unsuccessful TAE of the GDA and required a laparotomy. Vascular ligation at the pancreatic head was successful in achieving hemostasis, but hepatic failure secondary to hemorrhagic shock proved fatal 59 days after the initial surgery (patient 10).
Figure 1Case 3. A 74-year-old woman with advanced gallbladder cancer presented with massive hemorrhage 10 days after pancreatoduodenectomy combined with partial hepatectomy of the segments (Couinaud segments) IVb and V. Angiogram of the common hepatic artery [the right hepatic artery (RHA) replaced from the celiac axis (CA)] showed a pseudoaneurysm (arrow) originating from the stump of the gastroduodenal artery (GDA). (A) Complete hemostasis was obtained using transcatheter arterial embolization of this stump. The patient survived without hepatic failure because the hepatic inflow was maintained by the replaced RHA (B). LHA Left hepatic artery, SPA splenic artery.Figure 2Case 4. A 69-year-old man who had undergone a pylorus preserving pancreatoduodenectomy for distal bile duct cancer had massive hemorrhage 24 days after surgery. Angiogram of the celiac axis (CA) showed a pseudoaneurysm (arrow) originating from the common hepatic artery (CHA) (A) Complete hemostasis was obtained using transcatheter arterial embolization proximally and distally to the origin of the pseudoaneurysm, but the proper hepatic artery was occluded. The hepatic arterial inflow was narrowly maintained via the left subphrenic artery (B). The patient had an uneventful course. RHA Right hepatic artery, LHA left hepatic artery, SPA splenic artery.
Of the two patients with a pseudoaneurysm originating from the SPA, one underwent TAE of the CA with a favorable outcome because the pancreatoduodenal arcades around the pancreatic head maintained hepatic inflow after DP (patient 11, Fig. 3). The other patient underwent an emergency laparotomy. Complete hemostasis was achieved by ligation, but hemorrhagic shock resulted in subsequent hepatic failure (patient 12).
Figure 3Case 8. A 77-year-old man who had undergone a distal pancreatectomy for pancreatic tail cancer had massive hemorrhage 17 days after surgery. Angiogram of the celiac axis (CA) showed a pseudoaneurysm (arrow) originating from the splenic artery (A). Hemostasis was obtained using transcatheter arterial embolization (TAE) of the CA. The common hepatic artery (CHA) was occluded by TAE but the hepatic inflow was maintained via the arcades of the pancreatic head from the superior mesenteric artery (B). The patient had a favorable course. RHA Right hepatic artery, LHA left hepatic artery, GDA gastroduodenal artery.
One patient with a pseudoaneurysm of the SMA underwent surgical resection with vascular reconstruction. However, the patient died of recurrent pancreatic cancer and multiple organ failure during the hospital stay (patient 13).
Seven of 13 patients died in the hospital; thus, the mortality rate for massive arterial hemorrhage was 54%, and the overall mortality rate was 2.0%.
Case reports of some patients are illustrated in Figs. 1, 2, and 3.
Discussion
Rupture of a pseudoaneurysm, although uncommon, can cause life-threatening hemorrhage even comparatively late after pancreatobiliary surgery.1–6 This morbidity rate for pancreatectomy was reported to range from 2.0% to 4.6%.4–6,11,12 A pseudoaneurysm is a pulsatile hematoma surrounded by fibrous tissue that communicates with the artery via a disruption of the arterial wall. It can rupture into the peritoneal cavity, the gastrointestinal tract, or biliopancreatic ducts through a point of weakness, most commonly the anastomotic site. The Japanese Multi-institutional Study of 1,066 patients who underwent PPPD reported that the incidence of intra-abdominal hemorrhage was 3.5% and that of upper gastrointestinal hemorrhage was 3.2%.23
The etiology of pseudoaneurysm formation has yet to be clearly delineated. It is believed to be most commonly due to pancreatic fistula or anastomotic dehiscence.1–4,10–12 However, pseudoaneurysm can develop far from the pancreatic cut surface, and there is no evidence of a pancreatic leak in some cases. It has been suggested that skeletonization of the visceral arteries may result in iatrogenic vascular injury (e.g., secondary to diathermy).10,14 In three patients in our series, the etiology was thought to be a minor vascular injury that occurred during dissection (see Table 1). Previous reports found that the patients with massive arterial bleeding frequently had septic complications.3,4,17 Therefore, both arterial injury and infection can contribute to massive arterial hemorrhage. Whether or not preoperative obstructive jaundice is an etiologic fact remains controversial.3,24
Some clinical studies found that a preliminary warning bleeding (sentinel bleeding) precedes major hemorrhage.1,2,9–13 This sentinel bleeding probably indicates local infection and an anastomotic leak.2 So, recognition of a sentinel bleeding and prompt intervention can be life-saving.
Angiography is necessary to identify the site of bleeding, and TAE is the treatment of choice to control massive bleeding and achieve hemodynamic stabilization. When performing TAE for a pseudoaneurysm, microcoils must be placed both proximally and distally to the origin, not within the pseudoaneurysm itself.11,25
When the origin of the pseudoaneurysm is distal to the PHA, left hepatic artery, RHA, or MHA, TAE should be highly selective to preserve the other branch to the liver. Selective TAE without devascularization of the other lobe provides optimal protection of the liver parenchyma (patient 1).15 Nevertheless, superselective TAE frequently is not possible. Inadvertent occlusion of PHA, even when bleeding is controlled, may cause fatal hepatic infarction (patient 2).10 Therefore, the success of superselective TAE distal to the PHA depends on the expertise of the radiologist.
Superselective TAE is difficult or even impossible for a pseudoaneurysm proximal to the PHA.24 When the GDA is ligated close to its divergence from the CHA, you must embolize the CHA to obtain hemostasis. The proximal and distal control of a bleeding pseudoaneurysm of the PHA or CHA usually results in complete occlusion of hepatic arterial flow. Fortunately, we successfully performed TAE of the GDA in patient 4 because the patient had the replaced RHA from CA, and it was unaffected by TAE. Even if the CHA is occluded, the prognosis is good when hepatic inflow can be maintained by a replaced hepatic artery,6,13,14 but success is not uniform. In another case, hepatic inflow was narrowly maintained by the left subphrenic artery after TAE of the CHA (patient 6). A similar case has been described previously.16 The liver can tolerate considerable arterial embolization because of its multiple collateral pathways, mainly via the subphrenic arteries. Unless the surgical procedure includes mobilization of both lobes of the liver, as long as the subphrenic arteries are well developed, TAE proximal to the PHA should lead to a successful outcome. However, TAE proximal to the PHA usually risks occlusion of the CHA with the attendant risk of necrosis and liver failure.9,17 The authors believe that the presence of a few collateral pathways might make liver abscesses difficult to treat and may be associated with high morbidity and mortality rates (patient 7).10 Complete interruption of arterial inflow to the remaining liver after major hepatectomy usually causes imminent hepatic failure (patients 8 and 9). Emergency laparotomy and vascular reconstruction are the most certain treatments for this type of bleeding, but preoperative angiography is highly recommended to identify the bleeding site, although surgery should not be excessively delayed. Endovascular stenting is another option in reestablishing the continuity of the bleeding artery, such as GDA, PHA, or CHA.19–22 A covered stent makes it possible to arrest the bleeding, while preserving patency. Potential disadvantages include longer duration to obtain hemostasis than TAE, technical difficulties in negotiating tortuous arteries, and the risk of arterial rupture due to low flexibility and fragile vascular walls. In the case of a stented hepatic artery, the progressive occlusion of the stent due to intimal hyperplasia would not influence outcome because this process is gradual and allows for the formation of collateral pathways.21 Therefore, a stent-graft delivered into a bleeding artery proximal to PHA may be the treatment of choice. When this procedure is technically difficult, vascular reconstruction should be performed after temporary occlusion by interventional radiology. When vascular reconstruction is difficult and ligation is required to obtain hemostasis, creation of an ileocolic arterioportal shunt is another option,26 which we performed successfully in patient 3. Thus, the indications for TAE proximal to the PHA are limited to cases where the replaced hepatic artery exists or the subphrenic arteries are well developed.
Pseudoaneurysm originating from the SPA is well described as a complication of pancreatitis,27,28 but this is an unusual source of bleeding after pancreatobiliary surgery. Selective TAE is indicated because ischemia of the spleen is rare. However, when the origin of the pseudoaneurysm is close to the CA, selective TAE proximal to the SPA is as difficult as the case of bleeding from the GDA. Therefore, when the SPA is divided in surgery, it may be better to leave the proximal part of the ligation site in some degree. TAE of the CA is contraindicated as it will completely interrupt hepatic arterial flow in most cases (patient 11).
When the origin of a pseudoaneurysm is the SMA, it may be extremely difficult or even impossible to preserve mesenteric arterial flow. Hence, resection of the pseudoaneurysm with vascular reconstruction is indicated (patient 11). Endovascular stenting may be an alternative deserving further study.
Hemorrhagic shock is a potentially fatal complication that may result in hepatic failure (patient 10). Rebleeding after TAE is a poor prognostic factor. As rebleeding is often due to a pancreatic leak or intraperitoneal septic condition, pancreatic drainage and loculated fluid collections are mandatory.6 The management of anastomotic dehiscence after pancreatectomy, whether a completion pancreatectomy is necessary or not, is controversial.1,6,29–33 When management of the dehiscence is difficult or when severe organ failure is present, completion pancreatectomy is probably necessary.1,6,29–31
Analysis of our experience and literature review suggests that management of a pseudoaneurysm must be individualized according to the site of bleeding (Fig. 4). We have developed a protocol for managing massive postoperative arterial hemorrhage and are evaluating it postoperatively in a prospective fashion. We hope to report the value of this approach in the future.
Figure 4Scheme for an approach to the management of a pseudoaneurysm according to the site of bleeding. PHA Proper hepatic artery, RHA right hepatic artery, MHA middle hepatic artery, LHA left hepatic artery, SPA splenic artery, GDA gastroduodenal artery, CHA common hepatic artery, CA celiac axis, SMA superior mesenteric artery, TAE transcatheter arterial embolization.

hemorrhage
transcatheter arterial embolization
pseudoaneurysm
pancreato-biliary surgery


Giant cervicothoracic extradural arachnoid cyst: case report

The pathogenesis, etiology, and treatment of the spinal arachnoid cyst have not been well established because of its rarity. A 57-year-old male was presented with spastic quadriparesis predominantly on the left side. His radiological examination showed widening of the cervical spinal canal and left neural foramina due to a cerebrospinal fluid - filled extradural cyst that extended from C2 to T2 level. The cyst was located left anterolaterally, compressing the spinal cord. Through a C4–T2 laminotomy, the cyst was excised totally and the dural defect was repaired. Several features of the reported case, such as cyst size, location, and clinical features make it extremely unusual. The case is discussed in light of the relevant literature.
Introduction
Various types of cystic lesions are confronted in the spinal canal and are classified in respect of their relationship to the adjacent structures and nature of the cyst content. Amongst them, cerebrospinal fluid (CSF)-filled meningeal cysts constitute for the majority of the cases [11, 18] and are called as “arachnoid cysts,” “diverticula,” [5, 9] or “pouches” [9]. They may be located in the intradural, extradural, or perineural spaces. Depending on the location, size, and mechanism of origin, the clinical course varies between asymptomatic, incidentally-diagnosed cases [17] to severe myelopathy [11]. When they communicate freely with subarachnoid space, fluctuating symptoms related to changes in CSF pressure may occur [8, 9]. Although arachnoid cysts can be observed anywhere along the length of the spinal canal, middle, and lower thoracic regions constitute for the most frequently involved areas. When progressive neurological findings exist, surgical treatment is warranted. Surgical techniques include excision, fenestration, or placement of a cysto - subarachnoid shunt [6, 11], as well as some less invasive techniques that have been proposed recently [16].
We present a case with a giant cervicothoracic extradural arachnoid cyst and its surgical management. Several features of the cyst, such as its size, location, and clinical features make the case extremely unusual.
Case Report
A 57-year-old male was referred with symptoms of difficulty in walking, weakness, numbness, and thinning of arms and legs, and impotency, which had all begun two years before. The patient had suffered a serious traffic accident when he was 10 years old, and has had a contracture of his right hand since then. Neurological examination revealed spastic quadriparesis predominantly on the left side (left upper extremity proximally had 2/5 muscle strength, distally had 1/5, and left lower extremity globally had 4/5), left-sided atrophy, hypoesthesia and hypoalgesia in C5 - C8 dermatomes, hypoactivity of deep tendon reflexes at the upper extremity, hyperactivity in patellar reflex, and Babinski sign. Muscle tonus of bilateral lower extremities was increased. The anal sphincter tonus was weak, and the patient reported an intermittent sphincter control defect.
Cervical radiographs showed widening of the left neural foramina and the spinal canal. Magnetic resonance imaging (MRI) revealed an extradural cystic mass extending from C2 to T2 vertebral bodies, located left anterolaterally, compressing the spinal cord (Figs. 1a, b, c and 2). It had the same CSF intensity on T1 and T2-weighted images and showed no contrast enhancement. The lesion had caused a concavity in the related vertebral bodies and widening of the neural foramina on the left side. Electrophysiological tests reported chronic severe neurogenic involvement and a delay in the somato - sensorial evoked potential responses in C6 - T1 innervated muscles.
Fig. 1T2-weighted median (a), slightly left paramedian (b), and left paramedian (c) sagittal magnetic resonance images of the cervical region shows a cystic mass extending from C2 to T2 vertebral bodies, located left anterolaterally, enlarging left neural foramina (arrows). (Arrowheads spinal cord)Fig. 2Axial magnetic resonance image taken from T1 level shows the CSF-filled extradural cyst, located left anterolaterally, compressing the spinal cord (SC spinal cord)
A C4 – T2 laminotomy was performed. An extradural cystic lesion, full of CSF and having a thin and transparent membrane, was observed compressing the dural sac. The lesion had caused widening of C5 – C7 foramina and there was an active flow of CSF to the cyst through the defects located at the exiting points of these three roots. The cyst wall was excised and the dural defects were repaired using muscle pieces and sutures. Despite some degree of the spinal cord and dural sac expansion, the epidural and subarachnoid spaces left enlarged, since the canal was widened. The epidural space was left unfilled for the fear of compression. The samples taken from the cyst wall were reported as fibrohyalinized meningeal tissues.
Postoperative course was uneventful. Although the spasticity gradually improved during two years of follow-up, muscle strength and other neurological findings did not change.
Discussion
Spinal arachnoid cyst is a rare entity. There are various classifications based on etiology, histopathology, or localization of the cysts. Many authors classify spinal meningeal cysts as both intradural and extradural.
Extradural cysts include arachnoid cysts, synovial cysts, ganglias, cysts of ligamentum flavum, and cysts originating from the intervertebral discs. Intradural cysts include arachnoid cysts, enterogen (endodermal, neuroenteric) cysts, and ependymal cysts [3, 6, 7, 10, 12 – 15, 18]. The pathogenesis of spinal arachnoid cyst is not clear and probably not homogenous. Congenital [13], traumatic [1], or inflammatory [15] mechanisms were proposed. It was documented that congenital asymptomatic cysts could enlarge due to trauma and become symptomatic [3]. The size of arachnoid cysts may vary in relation to underlying mechanisms. For example, the arachnoid cysts related to arachnoiditis are usually localized and small [6, 18]. Pulsatile CSF dynamics [9], osmotic gradient between the subarachnoid space and cyst [7], and the valve - like mechanism between the cyst and subarachnoid space [10] may play an important role in the enlargement of spinal extradural arachnoid cysts. Doita et al. [4] demonstrated that increased intra abdominal and intrathoracic pressure may lead to size changes of the spinal arachnoid cyst.
A review demonstrated that arachnoid cysts involving the cervical region are extremely rare, that they never exceed three vertebral bodies in length, and that none extended into the thoracic region [6], except the case reported by Safriel et al. [14]. That case was an intradural arachnoid cyst situated anteriorly to the spinal canal extending between C5 and T3 levels. The presented cyst was extradural, located at the cervicothoracic region, anterolateral to the spinal cord, and involved eight vertebral bodies extending from C2 to T2 level. To the authors’ knowledge, there is no extradural arachnoid cyst reported in the literature matching that size. The patient had no disposing factor other than trauma. He had suffered a serious traffic accident when he was a child and consequently had a contracture in his left upper extremity. Although there was an excessively long duration (45 years) between trauma and appearance of new symptoms attributable to the cyst, the concordance of the former neurological deficit and location of the cyst convinced us that the etiology of the cyst might have been the childhood trauma. During the surgery, we did not observe any laminar signs that indicated a sustained compression fracture on the posterior elements. Thus, stretching and partial avulsion of the roots may have caused arachnoid and dural tearing during the childhood trauma, causing subsequent collection of the CSF at the epidural space, communicating freely both subarachnoid space and dural sleeves of the roots. Indeed, the occurrence of multiple dural defects, through which the CSF exits, is very rare. This point makes an extra implication on the case and further supports the avulsion theory as the cause of multiple dural tearings, since the neurological deficit due to childhood trauma is concordant with multiple root involvement. Long-standing progressive enlargement of the cyst explains radiological signs such as eroded vertebral bodies and enlarged intervertebral foramina.
Conclusion
The pathogenesis, etiology, and treatment of the spinal arachnoid cyst have not been well established because of its rarity. Symptomatic cases require surgical intervention. For long segment involvements, hemilaminectomy or laminotomy, as was performed in the current case is preferable to laminectomy in order to prevent postoperative deformity. In surgery, dural defect should be closed after excision. Neurological recovery depends on the size of the cyst and degree and duration of the spinal cord compression. A long-standing spastic myelopathy is unlikely to have a significant improvement [2], as we observed in the current case. Except spasticity, the patient had no improvement on his neurological findings. Thus, in delayed cases, surgery may be taken and should be offered as a prophylactic intervention to prevent further impairment, rather than a curative one.
In conclusion, the case presented here is a very unusual occurrence of this rare entity. Although probably traumatic, it had extremely delayed clinical presentation, its location was unusual, and as an extradural cervicothoracic arachnoid cyst, it was the largest amongst those reported.

arachnoid cysts
surgical treatment
magnetic resonance imaging
spinal cord compression
spine