(no title)

Background Ureter injuries are the most dreaded complication in gynaecological surgery. Some risk factors for the occurrence of urinary tract injuries are known, but clear guidelines to prevent ureter injuries during laparoscopic hysterectomy (LH) are lacking. The aim of this study was to analyze all known ureter injuries that occurred during LH for a benign indication, in the Netherlands, in order to identify patient- and surgeon-related risk factors.

Ninety-five LH-performing gynecologists were asked to recall all cases of known ureter injuries during LH in their hospital. After identification of ureter injuries, a structured interview was performed with a questionnaire that focused on the identification of predisposing factors which could account for the cause of the injury.

Forty-one injuries were detected in 37 patients (4 bilateral ureter injuries) in a 20-year period. The questionnaire could be completed for 31 cases. Predisposing factors were retrospectively assessed and classified into categories: patient-related (i.e., deep infiltrating endometriosis, intraligamentary fibroids) (n=18), surgeon-related (insufficient experience and/or technique) (n=16), or both (insufficient experience and difficult case) (n=8). According to earlier-mentioned recommendations in a Delphi study among experts, in 48.4% of these ureter injury cases more than one of the recommended techniques or predisposing conditions were not applied or available. Only one ureter injury was diagnosed during the LH; the mean time to diagnose the injury was 29 days.

Incomplete learning curve, insufficient applied technique such as coagulation of the uterine artery without the use of an uterine manipulator and/or from the contralateral side and/or without previously performed ureterolysis in case of distorted anatomy may be considered as the main predisposing factors. 106 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7

Ureter injuries are the most dreaded complication in gynaecological surgery. The course of the ureter in the pelvis renders it liable to injury during gynaecological operations, particularly during hysterectomies 1. The reported incidence of ureter injuries during hysterectomies varies between 0 and 2.2% 2-7. The approach of the hysterectomy plays a role in this variation of incidence. A systematic review, including 29 randomized controlled trials (RCTs) comparing the laparoscopic with the abdominal and vaginal approaches, reported an Odds Ratio (OR) of 2.41 (95% CI: 1.21 - 4.82) for urinary tract injuries in the laparoscopic group compared to the abdominal group and an OR of 3.69 (95% CI: 1.11 - 12.24) comparing total laparoscopic hysterectomy (LH) with the vaginal approach 8. A learning curve with respect to urinary tract injuries has been reported. The risk of a ureter injury significantly decreased with increasing experience of the surgeon with a cutoff level of 30 performed LHs 5. The role of a learning curve has also been postulated in 2001 after the analyses of a large Finnish database, including all 10.110 hysterectomies performed because of a benign indication in 1996. The incidence of ureter injury decreased significantly from 2.2 to 0.5% when the surgeons had performed more than 30 LHs compared to those who performed 30 or fewer LHs 3. Ten years later, a substantially lower incidence of ureter injuries was reported during LH in the same database, which resembled the reported incidence during abdominal (0.3%) and vaginal hysterectomy (0.04%) 9. Nevertheless, ureter injuries also occur in the hands of experienced gynecologists, as the indication for LH is expanding and the difficulty of the operation is increasing 10. Some risk factors for the occurrence of urinary tract injuries are known, such as the presence of deep infiltrating endometriosis, dense adhesions, very large uteri and excessive bleeding 5. However, clear guidelines for indications, surgical experience, or surgical techniques to prevent ureter injuries during LH are lacking. Based on a recent consensus-based Delphi procedure (which is a method to achieve consensus in dealing with a complex problem by structuring a group communication process) among laparoscopic experts, several recommendations were formulated 11. Given the low incidence of ureter injuries, much can be learned from each individual case. In order to increase our knowledge, we performed a systematic search to identify and analyze all known ureter injuries that occurred during LH in the first twenty years after the introduction of this procedure in the Netherlands. The aim of this study was to identify patient- and surgeon-related risk factors for ureteral injuries during a laparoscopic hysterectomy.

Case selection We retrospectively analyzed all recalled ureter injuries that occurred in the Netherlands from 1991 to 2011 during a LH of all types: total laparoscopic hysterectomy (TLH), laparoscopic-assisted vaginal hysterectomy (LAVH), and laparoscopic supracervical 107 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 hysterectomy (LSH). In an attempt to identify all known ureter injuries during these procedures, we systematically contacted all gynecological departments in April 2009 in the Netherlands and asked for the names of all gynaecologists who performed or currently perform LHs. We contacted all LH-performing gynaecologists (n=95) by both mail and telephone and asked them to recall all cases of known ureter injuries during LH in their or any other hospital. In addition, we studied all available annual reports of the hospitals in the Netherlands from 2000 onward in order to identify additional ureter injuries. We contacted all LH-performing gynecologists again in 2011 and asked them to report all additional identified ureter injuries (Figure 1). All identified cases of ureter injuries were studied and responsible surgeons or first assistants were contacted for a structured interview using a questionnaire that focused on identifying predisposing factors that could account for the cause of the injury. All known cases were studied, surgical reports were reviewed for their various procedural steps, and recorded videos were studied if available.    LH‐performing hospitals  n=64  LH‐performing gynaecologists  n=95 Ureter injuries  identified  n=26  100 hospitals  in the  Netherlands  Additional  ureter injuries  diagnosed  n=11 Ureter injury cases  identified  n=37  Ureter injury cases  analyzed  n=31  Cases not analyzed  n=6  ‐ 4 lack of participation  ‐2 lack of information  2nd round  interrogation  of hospitals  and surgeons   (January 2011)  Interrogation  of hospitals  and surgeons  (April 2009)  Identification Enrolment Analysis  Figure 1. Flowchart for identifying ureter injury cases 108 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 Development of the questionnaire used during interviews The development of the questionnaire was based on a systematic literature search and a Delphi consensus procedure among gynecological laparoscopic experts in the field of LH 11. Most predominant consented factors and formulated recommendations to prevent ureter injuries during LH and to prevent a delay in its diagnosis were integrated in our questionnaire. These factors could be (1) patient-related (i.e., indication for surgery, size of the uterus, presence of intraligamentary fibroids, deep infiltrating endometriosis, dense adhesions, previous abdominal surgery and other comorbidity); (2) surgeon-related (i.e., surgical team, learning curve, annual case load); (3) procedure-related (i.e., equipment and protocols used, level of identification or dissection of the ureter); and (4) diagnostic process during or after surgery in order to identify or exclude a ureter injury. We asked all surgeons what they thought was the main predisposing factor and their subjective observation and beliefs about the cause of the ureter injury in their particular case. We asked them if this ureter injury case changed their common practice with respect to patient selection, applied technique, or instruments used. Data collection and Analysis In order to identify the most common predisposing and potential causative factors of ureter injuries, we critically studied all cases; recorded baseline characteristics, applied techniques, and instruments used; and recorded presentation and timing of related symptoms, applied diagnostic methods, and findings during ureter reconstruction or performed therapy, its side, and location. We compared potential predisposing factors in each individual case with the previous agreed upon recommendations 11. All results were analyzed using the SPSS® version 16.0 statistical software package (SPSS Inc., Chicago, IL, USA).

Number of injuries The laparoscopic hysterectomy was first performed in the Netherlands in 1991. Of the 100 hospitals in the Netherlands, 64 performed LHs over time. After the initial round of interrogating the LH-performing gynecologists, 26 ureter injury cases were identified (Figure 1). The survey was repeated in 2011 and 11 additional cases of ureter injuries were identified, resulting in a total of 41 injuries in 37 patients (four women had bilateral ureter injuries). The reported injuries occurred between April 1994 and November 2010. The cases were identified in 25 different hospitals: 3 university hospitals, 12 general teaching hospitals, and 10 nonteaching hospitals. The questionnaire could be completed in 31 cases. Of the other six cases, the available data were insufficient to complete the questionnaire. In these cases only some of the questions could be answered (Figure 1). 109 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 Table 1. Baseline patient characteristics TLH (N=22) LAVH (N=6) LSH (N=3) Total (N=31) Age (mean ± SD) (years) 45.3 46.0 43.7 45.3 ± 7.1 BMI (mean ± SD) (kg/m 2) 27.0 27.8 - 27.1 ± 4.4 Parity (mean) 2.0 1.6 2.7 2.0 ± 1.17 ≥ 1 caesarean section [n(%)] 4 0 1 5 (16) Prior abdominal surgery a [n(%)] 9 2 0 11 (35.5) Indication for hysterectomy [n(%)] Abnormal bleeding 13 3 3 19 (61.3) Pelvic pain 4 2 0 6 (19.4) Other 5 1 0 6 (19.4) Fibroids [n(%)] 14 3 3 20 (64.5) a Other than caesarean section Patient baseline characteristics In the identified cases with ureter injuries, the main registered indication for performing LH was an uterine bleeding disorder (Table 1). Body mass index (BMI) ranged from 21.5 to 39.0, with a mean of 27.1 (SD 4.4). Previous abdominal surgery (other than caesarean section) was present in 11 patients (35.5%). In four cases (12.9%), deep infiltrating endometriosis was observed. Uterine fibroids were present in 20 of the 31 cases (64.5%); one had a large fibroid with an intraligamentary location. The uterine weight ranged from 60 to 896 g (mean = 271.4 g, SD = 211.2), and in 11 cases (35.5%) it was >250 g. Dense adhesions were present in seven patients (22.6%). Surgeon-related factors The total number of previous performed LHs by the first surgeon before the injury occurred ranged between 2 and 300, with a mean of 69.5 (SD = 78.0). The annual case-load of LHs ranged from 5 to 75, with a mean of 19.4 (SD = 13.9). In 18 cases (58.1%), the primary surgeon had performed fewer than 60 previous LHs, and in 11 cases (35.5%) fewer than 30 LHs. In eight cases (25.8%), the experience of the surgical team was fewer than 30 LHs, i.e., the first surgeon and the primary assistant had both performed fewer than 30 LHs before the particular ureter injury case occurred. Operative procedure Equipment A uterine manipulator had been used in 26 cases (83.9%), and in the majority of the cases it was a Clermont Ferrand manipulator (54.8%) (Table 2). In two cases no manipulator was used and in three cases the surgical report was unclear and the item could not be recalled by the surgeon. In general, three or more trocars were placed (90.3%). In one case only one additional trocar was used besides the optical trocar. Single port 110 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 was not used in these cases. Modalities used to achieve hemostasis of the uterine vessels during LH were conventional bipolar coagulation, vessel sealing, and ultrasonic technique (Table 2). In case of a bleeding (n = 9), the most common instrument used to achieve hemostasis was a conventional bipolar coagulating instrument. Procedure and surgical outcome Procedural aspects and surgical outcome in terms of operating time and blood loss are reported in Table 2. Of the 31 cases, there were 22 TLHs, 6 LAVHs, and 3 LSHs. In eight cases, a concomitant salpingo-oophorectomy (uni- or bilateral) was performed Table 2. Operative proc edure TLH (N=22) LAVH (N=6) LSH (N=3) Total (N=31) Equipment Uterine manipulator [n(%)] Clermont Ferrand 12 2 3 17 (54.8) McCartney tube 2 0 0 2 (6.5) Other with vaginal shield a 3 0 0 3 (9.7) Other without vaginal shield b 1 3 0 4 (12.9) Unknown 2 1 0 3 (9.7) None 2 0 0 2 (6.5) Haemostatic instrument [n(%)] Vessel sealing 13 2 0 15 (48.4) Ultrasonic 1 2 0 3 (9.7) Conventional bipolar 6 1 3 10 (38.7) Unknown 2 1 0 3 (9.7) Procedure Concomitant salpingo-oophorectomy [n(%)] 7 1 0 8 (25.8) Ureter handling Visualization ureter [n(%)] 6 1 2 9 (29.0) Window in broad ligament [n(%)] 7 0 0 7 (22.6) Lateralizing ureter [n(%)] 6 1 0 7 (22.6) Dissection ureter [n(%)] 1 0 0 1 (3.2) Vaginal closure vaginal cuff [n(%)] 6 5 - 11 (35.5) Outcome Blood loss (mean ± SD) (mL) 184.3 425.0 316.7 245.7 ± 288.4 Operating time (mean ± SD) (min) 137.0 149.8 174.3 143.5 ± 53.8 TLH total laparoscopic hysterectomy, LAVH laparoscopic-assisted vaginal hysterectomy, LSH laparoscopic supracervical hysterectomy a Pelosi, Colpo probe, Hohl-manipulator b V-care 111 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 (Table 2). The uterine arteries were coagulated from the ipsilateral side in 17 cases, from the contralateral side in 7 cases, and the surgeon could not recall the applied direction in 7 cases. We asked all surgeons whether or which perioperative measures were taken to identify or dissect the ureter (Table 2B). Preventive placement of ureter stents pre- or intraoperatively was not done. Diagnosis Ureter injury was identified between 0 and 260 days after surgery; one ureter injury was identified during primary surgery and in four cases within 1 week after the operation. Most cases (90.3%) were identified within 1 month after primary surgery, with a mean delay of 29 days (SD = 54) (Table 3). In 67.7% (21/31) of the cases, the ureter injury was located on the right side and in four cases it was bilateral. Most of the injuries (87.1%) were located at the distal third part of the ureter (Figure 2). The only patient with a proximal location of the ureter injury had an uterus of 896 g with a large intraligamentary fibroid. In one case an intravenous excretory urography was performed during the primary surgery because of a suspected ureter injury possibly resulting from difficult hemostasis. The urologist had already been consulted because of a bladder injury during the same procedure. Since stenting the ureter at the right side during cystoscopy failed, he decided to perform ureterolysis using an open approach, followed by a neo-implantation of the ureter in the bladder because of a detected injury. In the other 30 cases no diagnostic

were applied during primary surgery. In one case a Doppler ultrasound of the bladder was performed in the postoperative admission period. Due to a double ureter at the injured side, ureteral flow was observed at both sides despite the injury. The most common clinical signs and symptoms of ureter injury were abdominal and/or flank pain (58.1%), fever (16.1%), and urine leakage (12.9%). The most common applied diagnostic methods used to detect the injury were intravenous pyelogram Table 3. Time of recognition ureter injuries Moment of diagnosis [n(%)] TLH (N=22) LAVH (N=6) LSH (N=3) Total (N=31) During primary operation 0 1 0 1 (3.2) During postoperative admission 0 0 0 0 During re-admission 19 5 3 27 (87.1) Postoperative pain 11 4 3 18 (58.1) Postoperative fever 4 1 0 5 (16.1) Postoperative vaginal leakage of urine 4 0 0 4 (12.9) Unknown 3 0 0 3 (9.7) Time until identification (mean ± SD) (days) 37.4 ± 63.7 10.2 ± 5.8 8.7 ± 4.0 29.0 ± 54.0 TLH total laparoscopic hysterectomy, LAVH laparoscopic-assisted vaginal hysterectomy, LSH laparoscopic supracervical hysterectomy 112 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7       2 (including 1  bilateral)  18 (including  3 bilateral)  0  2 (including 1  bilateral)  12 (including  3 bilateral)  1  Figure 2. Localization and number of ureter injuries. The circled areas are the anatomical sites where the ureter is most likely to be injured during the laparoscopic hysterectomy (figure published in Baggish MH, Karam MM (2006) Surgical Anatomies of the bladder and ureter. In: Atlas of Pelvic Anatomy and Gynecologic Surgery. Philadelphia: Saunders © Elsevier). (n = 8), computed tomography with contrast (n = 8), and (Doppler) ultrasound of the kidney and bladder to assess the ureteral flow (n = 7). Treatment and outcome All ureter injuries were repaired by urologists, and ureter catheterization was carried out in 26 of the 35 ureter injuries. Successful retrograde stenting was performed for 12 injured ureters. In 14 cases stenting was not possible via the retrograde route so an antegrade passage by means of a nephrostomy was used. Subsequent surgical repair was carried out in 22 patients, all by an open procedure. The repair modalities used were (1) “spontaneous” recovery after ureter catheterization (n = 9), of which one case per open surgery, (2) end-to-end anastomosis of the damaged ureter (n = 1), and (3) ureteroneocystostomy with or without psoas muscle hitch (n = 20). Immediate repair was carried out in one case that was discovered during primary surgery after 113 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 converting the operation to open surgery. Ureter stents were left in place after surgical repair in all cases and removed after a couple of weeks. As far as we know, all patients had a successful repair with normal kidney function and no urine incontinence. Predisposing factors Subjective retrospective judgment of possible predisposing factors of the ureter injury in their own case by the surgeons In ten cases (32.3%), an uneventful LH procedure was reported. Five surgeons reviewed the LH in retrospect as more difficult than expected. Nine surgeons rated the procedure as difficult, with a score of more than 5 (on a scale of 0 to 10). Surgical difficulties due to distorted anatomy were reported in eight cases (25.8%): dense adhesions (n = 7), deep infiltrating endometriosis (n = 4), and intraligamentary fibroids (n = 1). Heavy bleeding occurred in nine cases. Potential causal factors of the ureter injury, as reported by the surgeons, were extensive coagulation in case of a bleeding (n = 5), coagulation too lateral (n = 14), lack of previous experience with LH (n = 1), dissection too distal and lateral (n = 1), and distortion of normal anatomy (i.e., endometriosis, dense adhesions, and large fibroids) (n=4). In six cases the surgeon could not determine any possible predisposing factor. Nine gynecologists changed their surgical technique after the case. Mentioned changes were assistance from a more experienced gynaecologist during LH (n = 2), lateralization of the ureter during all LHs (n=2), routine use of an uterine manipulator (n = 1) or more than two trocars (n = 1), coagulating the uterine pedicle closer to the uterus (n = 1), routine visualization of the ureter at the end of the procedure, and in case of insufficient peristalsis of the ureter, performance of ultrasound of the bladder for the assessment of ureteral flow on the first postoperative day (n = 1). In one case with severe deep infiltrating endometriosis, it became clear, after reviewing the recorded video, that after opening the retroperitoneum and performing adhesiolysis at the pelvic side wall, the ureter was dislocated medially and firmly attached to the torus uteri (uterorectal space). Based on this case the responsible gynecologists changed their protocol: complete ureterolysis before any other steps are taken in case of deep infiltrating endometriosis or dense adhesions. We asked all gynecologists about their current policy with respect to ureter handling during their LHs. Seven gynecologists stated that they dissected the ureter during all LHs, 13 only if indicated (e.g., in case of distorted anatomy), and three gynaecologists stated “mostly not”. We also asked all gynecologists about their diagnostic methods for excluding any ureter injuries during routine LHs and in case of a suspected injury. Reported routine diagnostic methods were intraoperative cystoscopy in all cases (n = 1), cystoscopy in case of a suspected ureter injury (n = 4), and routine Doppler ultrasound of the bladder for ureteral flow detection (n = 1). Reported protocols with respect to intraoperative procedures in case of a suspected ureter injury included intravenous indigo carmine or methylene blue (n = 10), catheterization/stenting of the ureter (n = 7), visualization of the ureter (n = 3), and cystoscopy (n = 2). 114 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 Classification of potential predisposing factors by the authors Potential predisposing factors were retrospectively assessed by two of the authors (PJ and JH) and classified according the earlier-mentioned groups: patient-related (n = 18), surgeon-related (n = 16), or a combination of both (n = 8). Assuming that the recommendations, recently agreed upon by the experts in the Delphi study, to be the standard of care and the agreed upon protocol that should be followed when performing a LH 11, we assessed to what extent these recommendations were followed (Table 4). When a recommendation was not followed, we defined that as a “protocol violation”. a. The learning curve was proposed to be completed by 20 LHs in case of normal anatomy and normal-sized uteri and 30 in case of large uteri 11. In case of severe en- dometriosis or intraligamentary fibroids consensus on number needed to complete the learning curve was not reached, but it varied between 30 and >50 performed LHs. Thus, 11 cases (35.5%) may be considered as “protocol violations” with respect to the completed learning curve of the team, taking the anatomy into account. b. It was recently agreed upon that a uterine manipulator should always be used and the uterine pedicle should be coagulated close to the uterus with a perpendicular approach 11. The latter can be achieved only if the uterine pedicle is coagulated from the ipsilateral side. Thus, at this point, eight cases (25.8%) may be considered “protocol violations”. c. Visualization or dissection of the ureter was recommended in case of distorted anatomy. According to this recommendation, in 9 of the 31 cases, the ureter should have been identified; in seven of these nine cases the ureter was visualized and in one case the ureter was dissected. Thus, one case may be considered a “protocol viola - tion” with respect to ureter visualization or dissection in case of distorted anatomy. In 29 cases no standard intra- or postoperative cystoscopy or other diagnostic method was applied. No diagnostic method was used in cases of reported dense adhesions or deep infiltrating endometriosis (n = 7) or when a procedure was more difficult to perform then expected by the surgeon (n = 5). In one of these cases, protracted recovery by the patient, with the presence of abdominal pain and fever, was the reason to use additional diagnostic methods (cystoscopy, computed tomography, and intravenous excretory urography) on the fourth postoperative day. In the other cases the reported postoperative recovery period was judged to be uneventful during admission.

We performed a systematic search to obtain nationwide data on iatrogenic ureter injuries during laparoscopic hysterectomy for benign indications. To our knowledge this is the first individual patient analysis of such a large number of ureter injuries during this procedure. In more than one-third of the injury cases, the primary surgeon performed fewer than 30 laparoscopic hysterectomies, and in one-fourth of the cases, the entire team had performed fewer than 30 LHs. The learning curve for laparoscopic hysterectomy should be 115 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 Table 4. Predisposing factors of ureter injury cases and “protocol violation” d Case Years Patient-related a Surgeon-related b Patient-a and surgeon- brelated Ureter dissection Ureter handlingc “Protocol violation”d Laparoscopic assisted vaginal hysterectomy (LAVH) 1 1994 >12/395 g Team 12/560 g - - - 3 2006 <12/257 g - - - 4e 2008 <12/95 g 1st < 30; contralat. - - + 5 2009 <12 Team < 30 - - + 6 2010 12/224 g - - - 8e 2003 >12/490 g No manipulator + - - + 9 2006 >18/415 g Team < 30; contralat. + - + + 10 2006 896 g; intralig. fibroid Contralat. + - + + 11 2007 <12/127 g; adh. - + - 12 2007 <12/200 g Team < 30; contralat. - - + 13 2007 12/130 g - - - 15 2008 12; DIE/adh. + + - 17 2008 <12/120 g Team < 30 - - + 18 2008 <12 Team < 30 - - + 19 2008 <12 team<30 - - + 20 2009 <12; DIE/adh. 1st < 30 + - - + 21e 2009 <12/60 g + + - 22 2010 12/250 g - - - 24 2010 <12/100 g; DIE/adh. Team 12 - - - 26 2010 >12/258 g + + - 27 2010 <12; adh. Contralat. + + + + 28 2010 <12/135 g 1st < 30 - + - completed by 20-30 procedures for a “simple” LH with normal anatomy and small-sized uteri 3, 11, and more than 30 LHs are needed to complete the learning curve for complicated LH (intraligamentary fibroids, dense adhesions, distorted anatomy). In 45% of the ureter injury cases, the uteri were small (<12 weeks gestational age) and normal anatomy was present without any adhesions or endometriosis. In these cases a failure of the applied 116 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 Table 4. Continued Case Years Patient-related a Surgeon-related b Patient-a and surgeon- brelated Ureter dissection Ureter handlingc “Protocol violation”d Laparoscopic supracervical hysterectomy (LSH) 29 2006 >12/376 g; adh. + + - 30 2006 >12/618 g; DIE/adh. - + - 31 2009 >12/262 g Contralat. + - - + Total protocol violation [n(%)] 15 (48.4%) g uterine weight in grams, a dh. dense adhesions, DIE deep infiltrating endometriosis a Patient-related is defined as uterine size over 12 weeks gestation, existence of deep infiltrating endometriosis, and/ or dense adhesions and/or intraligamentary fibroids. Uterine size is expressed as size 12 weeks, or > 18 weeks of gestation (12 or > 18, respectively) and uterine weight in grams (g) b Surgeon-related is defined as the surgical team performed fewer than 30 previous LHs (<30 LHs) and/or the first surgeon performed fewer than 30 previous LHs ( 1 st < 30) and/or contralateral coagulation of the uterine pedicle (contralat.) and/or procedure performed without the use of an uterus manipulator (no manipulator) c Ureter handling is defined as ureter visualization and/or lateralizing of the ureter (e.g., making a window in the broad ligament) d Protocol violation is defined as deviation of the previous recommendations as agreed upon by the expert team in the Delphi procedure in order to prevent ureter injuries during laparoscopic hysterectomy 11 e Ureter injury at both sides technique or insufficient knowledge of the anatomy and equipment may have played a role. This suggestion is partly underlined by the fact that in more than half of the cases with a normal anatomy, the primary surgeon had previously performed fewer than 30 LHs. This is also in line with the 50% ureter injuries that occurred without any predisposing factor and in 30% of the cases in uncomplicated small-sized uteri in the Finnish database 2. The main difference between laparoscopic and total abdominal hysterectomy is the use of electrocoagulation of uterine vessels during laparoscopic procedures 2. Excessive electrocoagulation of uterine vessels and cardinal ligaments near the ureter increases the risk of ureter injuries. In addition, the electrical current may damage the vascular supply and perivascular tissue, leading to delayed tissue necrosis and lateral thermal damage. It is difficult to estimate the exact number of ureter cases related to coagulating activities. However, given the subjective judgement of the surgeons about the cause of ureter injuries, the delay in symptom presentation, and findings during ureter repair procedures, we estimate electrocoagulation to be involved in more than half of our cases. There does not seem to be a relationship with the type of instrument used for coagulation. Given the lack of comparative studies on ureter injuries or complications as the end point, the optimal coagulating instrument to be used during laparoscopic hysterectomies can not be defined. As proposed previously, the level of experience is probably more important in preventing urinary tract injuries than the type of instrument used 11. Identification, dissection and lateralization of the ureter before securing the uterine arteries are proposed by several authors to prevent ureter injuries 12-14. Although the ureter may often be visualized through the peritoneum in the upper pelvis, it cannot be identified reliably in the area of the cardinal ligaments. Particularly in the presence 117 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 of distorted anatomy due to endometriosis or fibroids, the peritoneum is thickened and fibrosis retracts the ureter closer to the uterus 15. Lateralization of the ureter during the so- called “Koh manoeuvre”, which is supposed to prevent ureter injuries 12, is mostly difficult to achieve when there is of distorted anatomy, so ureterolysis is required in these cases to identify and free the ureter. In a systematic Delphi procedure, it was not recommended that ureterolysis should be performed on a routine basis but only in patients with distorted anatomy near the uterine artery 11. Only one case (4%) of the known ureter injury locations was located at the pelvic side wall. Furthermore, in seven cases the ureter was lateralized from the operating field. It is not clear if in all these cases the lateralization was performed using the Koh manoeuvre. However, distortion of the anatomy was present in five of these seven cases, complicating the performance of a successful Koh manoeuvre. This shows that visualization of the ureter at the pelvic side wall is not sufficient and that visualization or complete ureterolysis up to the uterine vessels should have been considered, particularly in case of distorted anatomy or large uteri. Recommendations for the applied technique in order to reduce the risk on urinary tract injuries were previously agreed upon by experts in a Delphi consensus procedure 11. In comparison to the previously reported agreed upon recommendations, in 48.4% of the cases not all of these recommendations were followed. We called them protocol violations. Strictly speaking, this is not the correct term to use since all cases were performed before the recommendations were published and up to now there is no approved guideline on this subject in the Netherlands. In addition, it can not be proven that all ureter injuries would have been prevented if the recommendations had been followed in all cases. However, some of these recommendations, such as the use of an uterine manipulator, are easy to implement. To prevent long-term complications such as urinoma or reduced kidney function, ureter injuries should be recognized as soon as possible. An ureter injury is repaired more easily if discovered intraoperatively and patients would not need to be subjected to a second major unplanned extensive reoperation. In our study, the mean time to diagnose a ureter complication was almost 1 month. This is in line with other studies. Intraoperative detection of ureter injuries has been reported in only 5-13% of the cases 2, 7, 16. Among the acute injuries of the urinary tract, ureter injuries are the most difficult to recognize as there often may be few or no symptoms 1. Indeed, in our cases only one patient had a recognized protracted primary postoperative recovery and only one injury was discovered at the time of the primary surgery. Most of the surgeons do not apply standard additional intra- or postoperative diagnostic screening methods, including intravenous dye injection, ultrasonography, or cystoscopy to assess ureteral outflow in the bladder, to exclude ureter injury. Whether these diagnostic methods would have identified all ureter injuries in our cases is a matter of debate. Several studies proposed routine use of intraoperative cystoscopy to assess the ureter flow as a part of all LHs 17-19. Cystoscopy during LH is well tolerated and can reassure surgeons of immediate urinary tract injuries, but it is not useful in identifying patients who may later fistulize 18. Given the low incidence of ureter injuries, it is an additional time-consuming procedure that is not required in most patients. Cystoscopy during LHs was postulated to be cost-effective if the rate of 118 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7 ureter injury exceeded 2% 19. Thus, the agreed upon advise of the expert panel to apply additional intraoperative ultrasound or cystoscopy only in patients with increased risk on ureter injuries, i.e., patients with distorted anatomy or very large uteri, seems to be logical in terms of cost-effectiveness. Given the possible relation between ureter injuries and an incomplete learning curve of the primary surgeon, we should start a discussion on whether intraoperative cystoscopy or Doppler ultrasound to assess ureteral flow should be performed on a routine base during all LHs performed by surgeons during their learning curve. It would be interesting to calculate the number needed to diagnose; however, this was not possible in our study given the lack of baseline characteristics of patients who had LHs in the past 20 years in the Netherlands without an ureter injury. Because of the retrospective design of this study and the presence of a recall bias, the total reported number of injuries should be considered incomplete. This also underlines the need for prospective registration of all LHs, its baseline characteristics, and complications. In conclusion, insufficient experience of the surgeon with the applied technique and distortion of the anatomy by pelvic disease (e.g., endometriosis) are predisposing factors for ureter injuries. The earlier agreed upon recommendations by the Delphi study, such as the relevance of surgical experience of the surgical team, the use of an uterine manipulator, coagulation of the uterine pedicles from the ipsilateral side, and complete ureterolysis in case of distorted anatomy, are confirmed in this study. In addition, intraoperative cystoscopy or sonography to assess ureteral flow should be considered in these cases. Based on the previous Delphi study and on the current study, we propose recommendations in order to prevent ureter injuries during LHs and to promote its early detection (Table 5). Table 5. Recommendations by the authors for performing the laparoscopic hysterectomy with respect to preventing ureter injuries Preoperatively 1 Completion of learning curve (i.e., at least 30) with tutor (surgeon with sufficient experience and qualifications) Intraoperatively 2 Use appropriate instruments: e.g., uterus manipulator 3 Coagulate uterine vessels close to the uterus from ipsilateral side with a perpendicular approach; i.e., minimizing risk on bleeding and enlarge distance between uterine artery and ureter 4 Completea ureter visualization in case of distorted anatomy before coagulation can take place Postoperatively 5 In case of distortion of anatomy and/or bleeding, performing cystoscopy during surgery or Doppler ultrasound ureteral flow on first postoperative day 6 Before completion of the learning curve, perform recommendation no. 5 in all cases, also in case of normal anatomy General recommendation 7 Nationwide prospective registration of all operative procedures, including baseline characteristics and complications a Complete is defined as visualization of the ureter in the course of the operation field (in the pelvis). This includes opening of the peritoneum and, if required, ureterolysis 119 ANALYSIS OF URETER INJURIES DURING LAPAROSCOPIC HYSTERECTOMY 7

We are very grateful to the participating gynecologists for reporting their cases and collaborating in the analysis.

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