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08.12.2016 | Ausgabe 8/2017 Open Access

Surgical Endoscopy 8/2017

Laparo-endoscopic versus open recurrent inguinal hernia repair: should we follow the guidelines?

Zeitschrift:
Surgical Endoscopy > Ausgabe 8/2017
Autoren:
F. Köckerling, R. Bittner, A. Kuthe, B. Stechemesser, R. Lorenz, A. Koch, W. Reinpold, H. Niebuhr, M. Hukauf, C. Schug-Pass
 

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Compared with primary inguinal hernia operations, both open and laparo-endoscopic recurrent repair procedures are associated with a higher rate of perioperative complications, re-recurrences and chronic pain [1, 2]. Six meta-analyses are available for comparison of laparo-endoscopic with open recurrent inguinal hernia repairs [38]. These meta-analyses analyzed 12 studies [920]. Compared with the meta-analysis by Li et al. [7], which included non-randomized studies [12, 13, 16, 19], the meta-analysis by Pisanu et al. [6] featured the largest number of exclusively prospective randomized studies [9, 11, 14, 15, 17, 18, 20]. There was no high risk of bias in any of the included trials [6]. The studies included in total 647 patients with recurrent inguinal hernia randomized to either laparo-endoscopic repair [n = 333; 51.5%, transabdominal preperitoneal patch plasty (TAPP) and totally extraperitoneal patch plasty (TEP)], or anterior open repair (n = 314; 48.5%, by Lichtenstein technique). Patients who underwent laparo-endoscopic repair experienced significantly less chronic pain (9.2 vs 21.5%; p = 0.003). Patients of the laparo-endoscopic group had a significantly earlier return to normal daily activities (13.9 vs 18.4 days, SMD −0.68, 95% CI −0.94 to −0.43; p < 0.000001). Operative time was significantly longer in laparo-endoscopic operations (62.9 vs 54.2 min, SMD 0.46, 95% CI 0.03, 0.89; p = 0.04) [6]. No other differences were found [6]. Another prospective randomized controlled study that was not included in the meta-analyses also identified a lower chronic pain rate after laparo-endoscopic recurrent repair [21]. A Swedish registry study likewise demonstrated on comparing anterior mesh repair with laparo-endoscopic mesh repair for recurrent hernias a lower risk of chronic pain for the laparo-endoscopic operation (OR 0.54 [CI 0.30–0.97]; p = 0.039) [22].
On the basis of the meta-analyses, the European Hernia Society recommends laparo-endoscopic inguinal hernia repair of recurrent hernias after conventional open repair [8, 23] and for recurrent hernias after laparo-endoscopic hernia repair an open procedure. Likewise, the International Endohernia Society recommends, with a high level of evidence, TEP and TAPP for repair of recurrent hernia as the preferred alternative to tissue repair and to the Lichtenstein repair after prior anterior repair [24, 25]. In the Consensus Development Conference of the European Association of Endoscopic Surgery, TEP and TAPP are preferred in patients with a recurrent groin hernia after open repair. Repeat endoscopic repair is only feasible when the surgeon has a high level of experience in repeat endoscopic groin hernia repair [26]. However, registry data show that even following previous open suture and mesh repair to treat the primary inguinal hernia, open suture and mesh repair are used once again for a recurrent hernia [27]. That is due to the fact that the skill needed for laparo-endoscopic recurrent inguinal hernia repairs was not always assured. Where surgeons had used an open technique to repair 95% of primary inguinal hernias, then more than 90% of recurrences were also repaired using an open procedure [28]. That was also true when using mesh repair for the primary inguinal hernia operation [13].
This present analysis of data from the Herniamed Hernia Registry [29] now investigates: (1) To what extent surgeons implement the guidelines of the international hernia societies. (2) Since to date no study has compared the outcomes of open and laparo-endoscopic recurrent inguinal hernia repair carried out in compliance with the guidelines, that aspect will now also be explored in the present analysis. (3) Finally, how the outcomes of open and laparo-endoscopic recurrent inguinal hernia repair differ on compliance versus non-compliance with the guidelines.

Patients and methods

The Herniamed Registry is a multicenter, Internet-based hernia registry [29] into which 427 participating hospitals and surgeons engaged in private practice (Herniamed Study Group) have entered data prospectively on their patients who had undergone routine hernia surgery and signed an informed consent to participate. All postoperative complications occurring up to 30 days after surgery are recorded. On 1-year follow-up, postoperative complications are once again reviewed when the general practitioner and patient complete a questionnaire. Information is also obtained on any recurrence, pain at rest and on exertion as well as pain requiring treatment. This present analysis compares the prospective data collected for all male patients with a minimum age of 16 years who had undergone elective recurrent unilateral inguinal hernia repair using either transabdominal preperitoneal patch plasty (TAPP), total extraperitoneal patch plasty (TEP) or open repair in Lichtenstein, Should ice, TIPP and Plug techniques.
In total, 4812 patients were enrolled between September 1, 2009, and August 31, 2013 (Fig. 1). Of these patients, 2482 (51.58%) had laparo-endoscopic and 2330 (48.42%) open repair. All the patients had to have a 1-year follow-up (follow-up rate 100%).
The demographic and surgery-related parameters included age (years), BMI (kg/m2), ASA classification (I, II, III–IV) as well as EHS classification (hernia type: medial, lateral, femoral, scrotal and defect size: grade I = <1.5 cm, grade II = 1.5–3 cm, grade III = >3 cm) [30] and general risk factors (nicotine, COPD, diabetes, cortisone, immunosuppression, etc.). Risk factors were dichotomized, i.e., ‘yes’ if at least one risk factor is positive and ‘no’ otherwise.
The dependent variables were intra- and postoperative complication rates, number of reoperations due to complications as well as the 1-year results (recurrence rate, pain at rest, pain on exertion and pain requiring treatment).
All analyses were performed with the software 9.2 (SAS 9.2 Institute Inc. Cary, NY, USA) and intentionally calculated to a full significance level of 5%, i.e., they were not corrected in respect of multiple tests, and each p value ≤0.05 represents a significant result. To discern differences between the groups in unadjusted analyses, Fisher’s exact test was used for categorical outcome variables and the robust t-test (Satterthwaite) for continuous variables.
To rule out any confounding of data caused by different patient characteristics, the results of unadjusted analyses were verified via multivariable analyses in which, in addition to laparo-endoscopic or open operation, other influence parameters were simultaneously reviewed.
To identify influence factors in multivariable analyses, the binary logistic regression model for dichotomous outcome variables was used. Estimates for odds ratio (OR) and the corresponding 95% confidence interval based on the Wald test were given. For influence variables with more than two categories, one of the latter forms was used in each case as reference category. For age (years) the 10-year OR estimate and for BMI (kg/m2) the five-point OR estimate were given. Results were presented in tabular form, sorted by descending impact.

Results

1.
To what extent do surgeons follow the guidelines?
 
In the laparo-endoscopic recurrent operation group, the recurrent operation was performed for n = 1528/2482 (61.6%) patients following the open suture technique for n = 718/2482 (28.9%) after open mesh repair, and for n = 233/2482 (9.4%) following laparo-endoscopic primary mesh repair (unknown 0.1%).
Open recurrent repair was performed for n = 1011/2330 (43.4%) patients following previous open suture repair, for n = 897/2330 (38.5%) patients following laparo-endoscopic mesh repair and for 412/2330 (17.7%) patients after open mesh repair of the primary inguinal hernia (unknown 0.4%).
Accordingly, in the laparo-endoscopic recurrent repair group 90.5%, and in the open recurrent repair group 38.5%, of patients were operated on in compliance with the guidelines of the international hernia societies.
2.
Is there a difference in the outcome of open versus laparo-endoscopic recurrent inguinal hernia repair in compliance with the guidelines?
 
This analysis is based on n = 2246 laparo-endoscopic recurrent inguinal hernia repair operations following previous open primary operation and n = 897 open recurrent inguinal hernia repair operations following previous laparo-endoscopic primary repair (Table 1). Unadjusted analysis did not find any significant difference in the mean age between the two groups; however, the mean BMI value was higher for those patients undergoing open recurrent repair (Table 2). The open recurrent repair was associated with significantly larger hernia defects, more medial, fewer femoral and lateral EHS classifications (Table 3). No differences were identified in the risk factors (Table 3). Non-adjusted analysis of the target variables revealed that the intraoperative complications entailed more nerve injuries for open recurrent repair as well as more pain at rest and pain on exertion on 1-year follow-up (Table 4). No significant difference was detected between the laparo-endoscopic and open technique on performing recurrent repair in compliance with the guidelines for the following: overall intraoperative complication rate, postoperative complication rate, complication-related reoperation rate, recurrence rate and the rate of chronic pain requiring treatment.
Table 1
Recurrent operations according to the guidelines and previous operations
 
Previous operations
Total
Unknown
Suture
Open mesh
Endoscopic mesh
N
%
N
%
N
%
N
%
N
%
Recurrent operation
 Endoscopic
3
0.1
1528
61.6
718
28.9
233
9.4
2482
100.0
 Open
10
0.4
1011
43.4
412
17.7
897
38.5
2330
100.0
 Total
13
0.3
2539
52.8
1130
23.5
1130
23.5
4812
100.0
Bold numbers are the operations in accordance with the guidelines
Table 2
Age and BMI of patients with laparo-endoscopic versus open unilateral recurrent inguinal hernia repair in men according to the guidelines
  
Operation
p
Endoscopic
Open
Age (years)
Mean ± STD
58.9 ± 15.6
59.3 ± 15.3
0.440
BMI (kg/m2)
Mean ± STD
25.9 ± 3.4
26.3 ± 3.6
0.004
Table 3
Demographic and surgery-related parameters and risk factors for patients with laparo-endoscopic versus open unilateral recurrent inguinal hernia repair in men according to the guidelines
  
Endoscopic
Open
p
n
%
n
%
ASA score
I
561
24.98
257
28.65
0.091
II
1302
57.97
502
55.96
III/IV
383
17.05
138
15.38
Defect size
I (<1.5 cm)
417
18.57
151
16.83
<0.001
II (1.5–3 cm)
1459
64.96
493
54.96
III (>3 cm)
370
16.47
253
28.21
EHS-classification medial
Yes
1112
49.51
518
57.75
<0.001
No
1134
50.49
379
42.25
EHS-classification lateral
Yes
1351
60.15
452
50.39
<0.001
No
895
39.85
445
49.61
EHS-classification femoral
Yes
77
3.43
15
1.67
0.007
No
2169
96.57
882
98.33
EHS-classification scrotal
Yes
27
1.20
12
1.34
0.724
No
2219
98.80
885
98.66
Risk factor
 Total
Yes
687
30.59
275
30.66
0.966
No
1559
69.41
622
69.34
 COPD
Yes
151
6.72
66
7.36
0.534
No
2095
93.28
831
92.64
 Diabetes
Yes
129
5.74
51
5.69
1.000
No
2117
94.26
846
94.31
 Aortic aneurism
Yes
16
0.71
4
0.45
0.467
No
2230
99.29
893
99.55
 Immunosuppression
Yes
14
0.62
10
1.11
0.174
No
2232
99.38
887
98.89
 Corticoids
Yes
20
0.89
8
0.89
1.000
No
2226
99.11
889
99.11
 Smoking
Yes
262
11.67
110
12.26
0.669
No
1984
88.33
787
87.74
 Coagulopathy
Yes
33
1.47
9
1.00
0.390
No
2213
98.53
888
99.00
 Antiplatelet medication
Yes
202
8.99
79
8.81
0.890
No
2044
91.01
818
91.19
 Anticoagulation therapy
Yes
44
1.96
25
2.79
0.177
No
2202
98.04
872
97.21
Table 4
Intra- and postoperative complications, complication-related reoperations and 1-year follow-up results of patients with laparo-endoscopic versus open unilateral recurrent inguinal hernia repair in men according to the guidelines
  
Endoscopic
Open
p
n
%
n
%
Intraoperative complication
 Total
Yes
26
1.16
14
1.56
0.380
No
2220
98.84
883
98.44
 Bleeding
Yes
15
0.67
3
0.33
0.431
No
2231
99.33
894
99.67
 Injuries
  Total
Yes
17
0.76
12
1.34
0.147
No
2229
99.24
885
98.66
  Vascular
Yes
8
0.36
0
0.00
0.115
No
2238
99.64
897
100.0
  Bowel
Yes
5
0.22
0
0.00
0.330
No
2241
99.78
897
100.0
  Bladder
Yes
2
0.09
1
0.11
1.000
No
2244
99.91
896
99.89
  Nerve
Yes
0
0.00
9
1.00
<0.001
No
2246
100.0
888
99.00
Postoperative complication
 Total
Yes
80
3.56
33
3.68
0.916
No
2166
96.44
864
96.32
 Bleeding
Yes
29
1.29
17
1.90
0.248
No
2217
98.71
880
98.10
 Seroma
Yes
51
2.27
14
1.56
0.266
No
2195
97.73
883
98.44
 Bowell injury/anastomotic leakage
Yes
1
0.04
0
0.00
1.000
No
2245
99.96
897
100.0
 Wound healing disorders
Yes
2
0.09
4
0.45
0.059
No
2244
99.91
893
99.55
 Ileus
No
2246
100.0
897
100.0
Reoperations
Yes
27
1.20
9
1.00
0.714
No
2219
98.80
888
99.00
Recurrence on follow-up
Yes
28
1.25
10
1.11
0.858
No
2218
98.75
887
98.89
Pain in rest on follow-up
Yes
133
5.92
78
8.70
0.007
No
2113
94.08
819
91.30
Pain on exertion on follow-up
Yes
250
11.13
135
15.05
0.003
No
1996
88.87
762
84.95
Pain requiring treatment
Yes
85
3.78
40
4.46
0.419
No
2161
96.22
857
95.54
For multivariable analysis of intraoperative complications, complication-related reoperations and recurrence on 1-year follow-up, it was not possible to calculate any model because of the paucity of relevant cases. The results of the model that explored the variables influencing onset of postoperative complications are illustrated in Table 5 (model matching: p = 0.002). Only medial EHS localization impacted the postoperative complication rate. Medial EHS classification reduced the risk of postoperative complications (OR 0.427 [0.213; 0.857]; p = 0.017). But there was no evidence of the surgical technique having impacted the postoperative complication rate. The multivariable analysis results of pain at rest are presented in Table 6 (model matching: p < 0.001). Here, the BMI proved to be the strongest influence factor (p = 0.001). A five-point higher BMI increased the risk of pain at rest (five-point OR 1.351 [1.127; 1.620]). On the other hand, laparo-endoscopic operation (OR 0.643 [0.476; 0.868]; p = 0.004) and larger defect size (III vs I: OR 0.500 [0.307; 0.815]; p = 0.021) significantly reduced the risk of pain at rest. The multivariable analysis results of pain on exertion are given in Table 7 (model matching: p < 0.001). These were highly significantly affected by age and hernia defect size (p < 0.001). A higher age (10-year OR 0.825 [0.760; 0.897]) as well as larger hernias (II vs I: OR 0.704 [0.541; 0.916]; III vs I: OR 0.479 [0.331; 0.693]) reduced the risk of pain on exertion. Likewise, laparo-endoscopic operations (OR 0.679 [0.537; 0.857]; p = 0.001) compared with open operations reduced the risk for onset of pain on exertion. Similarly, lateral EHS classification reduced the risk (OR 0.624 [0.422; 0.922]; p = 0.018) of pain on exertion. However, the risk was increased in association with a five-point higher BMI (five-point OR 1.251 [1.081; 1.449]; p = 0.003). The multivariable analysis results of chronic pain requiring treatment are presented in Table 8 (model matching: p = 0.005). Here, only the BMI proved to be a significant influence factor (p = 0.014). A five-point higher BM increased the rate of pain requiring treatment (five-point OR 1.320 [1.058; 1.647]). However, there was no evidence of the surgical technique having impacted the rate of pain requiring treatment.
Table 5
Multivariable analysis of postoperative complications in patients with recurrent inguinal hernia repair according to the guidelines
Parameter
p value
Category
OR estimate
95% CI
EHS-classification medial
0.017
Yes versus no
0.427
0.213
0.857
Age (10-year OR)
0.081
 
1.148
0.983
1.339
Defect size
0.118
II (1.5–3 cm) versus I (<1.5 cm)
0.848
0.502
1.434
III (>3 cm) versus I (<1.5 cm)
1.382
0.756
2.526
Risk factors
0.139
Yes versus no
1.371
0.903
2.083
BMI (five-point OR)
0.155
 
0.807
0.600
1.085
ASA score
0.306
II versus I
0.817
0.486
1.370
III/IV versus I
1.177
0.600
2.308
EHS-classification lateral
0.372
Yes versus no
0.723
0.354
1.474
EHS-classification femoral
0.647
Yes versus no
1.263
0.466
3.426
Operation
0.772
Endoscopic versus open
0.939
0.616
1.434
EHS-classification scrotal
0.862
Yes versus no
1.121
0.308
4.077
Table 6
Multivariable analysis of pain in rest in 1-year follow-up in patients with recurrent inguinal hernia repair according to the guidelines
Parameter
p value
Category
OR estimate
95% CI
BMI (five-point OR)
0.001
 
1.351
1.127
1.620
Operation
0.004
Endoscopic versus open
0.643
0.476
0.868
Defect size
0.021
II (1.5–3 cm) versus I (<1.5 cm)
0.794
0.562
1.123
III (>3 cm) versus I (<1.5 cm)
0.500
0.307
0.815
Age (10-year OR)
0.064
 
0.902
0.809
1.006
EHS-classification lateral
0.087
Yes versus no
0.629
0.370
1.070
EHS-classification medial
0.122
Yes versus no
0.659
0.389
1.118
Risk factor
0.129
Yes versus no
1.278
0.931
1.754
EHS-classification femoral
0.834
Yes versus no
0.913
0.392
2.130
ASA score
0.888
II versus I
0.917
0.643
1.307
III/IV versus I
0.943
0.552
1.610
EHS-classification scrotal
0.974
Yes versus no
0.000
0.000
I
I Infinity
Table 7
Multivariable analysis of pain on exertion in 1-year follow-up in patients with recurrent inguinal hernia repair according to the guidelines
Parameter
p value
Category
OR estimate
95% CI
Age (10-year OR)
<0.001
 
0.825
0.760
0.897
Defect size
<0.001
II (1.5–3 cm) versus I (<1.5 cm)
0.704
0.541
0.916
III (>3 cm) versus I (<1.5 cm)
0.479
0.331
0.693
Operation
0.001
Endoscopic versus open
0.679
0.537
0.857
BMI (five-point OR)
0.003
 
1.251
1.081
1.449
EHS-classification lateral
0.018
Yes versus no
0.624
0.422
0.922
EHS-classification scrotal
0.094
Yes versus no
0.178
0.024
1.339
EHS-classification medial
0.180
Yes versus no
0.765
0.517
1.131
Risk factor
0.512
Yes versus no
1.087
0.847
1.393
ASA score
0.764
II versus I
0.981
0.749
1.285
III/IV versus I
1.114
0.737
1.682
EHS-classification femoral
0.933
Yes versus no
0.973
0.511
1.850
Table 8
Multivariable analysis of chronic pain requiring treatment in 1-year follow-up in patients with recurrent inguinal hernia repair according to the guidelines
Parameter
p value
Category
OR estimate
95% CI
 
BMI (five-point OR)
0.014
 
1.320
1.058
1.647
EHS-classification lateral
0.051
Yes versus no
0.494
0.243
1.004
Age (10-year OR)
0.053
 
0.871
0.758
1.002
EHS-classification medial
0.054
Yes versus no
0.501
0.248
1.012
ASA score
0.240
II versus I
1.048
0.654
1.679
III/IV versus I
1.607
0.834
3.094
Risk factor
0.253
Yes versus no
1.263
0.846
1.886
Operation
0.260
Endoscopic versus open
0.797
0.538
1.182
Defect size
0.294
II (1.5–3 cm) versus I (<1.5 cm)
0.944
0.597
1.493
III (>3 cm) versus I (<1.5 cm)
0.634
0.338
1.191
EHS-classification femoral
0.476
Yes versus no
1.390
0.561
3.445
EHS-classification scrotal
0.979
Yes versus no
0.000
0.000
I
I Infinity
3a.
How do the outcomes of laparo-endoscopic recurrent inguinal hernia repair differ on compliance versus non-compliance with the guidelines?
 
In the laparo-endoscopic recurrent operation group, the recurrent operation was performed for n = 233/2482 (9.4%) patients following laparo-endoscopic primary mesh repair, i.e., not in compliance with the guidelines of the international hernia societies (Table 9). These cases are compared below with the n = 2246/2482 (90.6%) patients who were operated on in compliance with the guidelines, with laparo-endoscopic procedure for recurrent repair following previous open primary inguinal hernia operation (Table 9). No significant difference was identified between the two groups with regard to the mean age and BMI (Table 10). The laparo-endoscopic recurrent repairs not conducted in compliance with the guidelines revealed a significantly higher proportion of larger defects as well as a smaller proportion of lateral inguinal hernia recurrences (Table 11). No relevant differences were found for the other variables and risk factors. When recurrent repair was performed as per the guidelines, the laparo-endoscopic procedure was found to be associated with fewer intraoperative (1.2 vs 3.0%; p = 0.019) and postoperative complications (3.6 vs 8.6%; p < 0.001) as well as a lower re-recurrence risk (1.2 vs 3.4%; p = 0.008; Table 12). No differences were identified for the pain rates.
Table 9
Laparo-endoscopic unilateral recurrent inguinal hernia repairs on compliance versus non-compliance with the guidelines
 
Previous operations
Total
Suture
Open mesh
Endoscopic mesh
N
ColPctN
N
ColPctN
N
ColPctN
N
ColPctN
Guidelines
 No
233
100.0
233
9.4
 Yes
1528
100.0
718
100.0
2246
90.6
 Total
1528
100.0
718
100.0
233
100.0
2479
100.0
Table 10
Age and BMI of patients with laparo-endoscopic unilateral recurrent inguinal hernia repair on compliance versus non-compliance with the guidelines
  
Guidelines
p
Yes
No
Age (years)
Mean ± STD
58.9 ± 15.6
60.1 ± 14.2
0.199
BMI
Mean ± STD
25.9 ± 3.4
26.2 ± 3.0
0.306
Table 11
Demographic and surgery-related parameters and risk factors for patients with laparo-endoscopic unilateral recurrent inguinal hernia repair on compliance versus non-compliance with the guidelines
  
Guideline
p
Yes
No
n
%
n
%
ASA score
I
562
24.99
59
25.32
0.992
II
1303
57.94
134
57.51
III/IV
384
17.07
40
17.17
Defect size
I (<1.5 cm)
419
18.63
34
14.59
0.001
II (1.5–3 cm)
1460
64.92
139
59.66
III (>3 cm)
370
16.45
60
25.75
Risk factor
 Total
Yes
687
30.55
60
25.75
0.129
No
1562
69.45
173
74.25
 COPD
Yes
151
6.71
14
6.01
0.681
No
2098
93.29
219
93.99
 Diabetes
Yes
129
5.74
10
4.29
0.361
No
2120
94.26
223
95.71
 Aortic aneurism
Yes
16
0.71
1
0.43
0.619
No
2233
99.29
232
99.57
 Immunosuppression
Yes
14
0.62
1
0.43
0.717
No
2235
99.38
232
99.57
 Corticoids
Yes
20
0.89
1
0.43
0.465
No
2229
99.11
232
99.57
 Smoking
Yes
262
11.65
30
12.88
0.580
No
1987
88.35
203
87.12
 Coagulopathy
Yes
33
1.47
3
1.29
0.827
No
2216
98.53
230
98.71
 Antiplatelet medication
Yes
202
8.98
15
6.44
0.191
No
2047
91.02
218
93.56
 Anticoagulation therapy
Yes
44
1.96
4
1.72
0.800
No
2205
98.04
229
98.28
EHS-classification medial
Yes
1115
49.58
120
51.50
0.576
No
1134
50.42
113
48.50
EHS-classification lateral
Yes
1351
60.07
118
50.64
0.005
No
898
39.93
115
49.36
EHS-classification femoral
Yes
77
3.42
6
2.58
0.493
No
2172
96.58
227
97.42
EHS-classification scrotal
Yes
27
1.20
5
2.15
0.223
No
2222
98.80
228
97.85
Table 12
Intra- and postoperative compilations, complication-related reoperations and 1-year follow-up-results of patients with laparo-endoscopic unilateral recurrent inguinal hernia repair on compliance versus non-compliance with the guidelines
  
Guidelines
p
Yes
No
n
%
n
%
Intraoperative complication
 Total
Yes
26
1.16
7
3.00
0.019
No
2223
98.84
226
97.00
 Bleeding
Yes
15
0.67
7
3.00
<0.001
No
2234
99.33
226
97.00
 Injury
  Total
Yes
17
0.76
3
1.29
0.388
No
2232
99.24
230
98.71
  Vascular
Yes
8
0.36
3
1.29
0.042
No
2241
99.64
230
98.71
  Bowell
Yes
5
0.22
0
0.00
0.471
No
2244
99.78
233
100.0
  Bladder
Yes
2
0.09
0
0.00
0.649
No
2247
99.91
233
100.0
Postoperative complication
 Total
Yes
80
3.56
20
8.58
<0.001
No
2169
96.44
213
91.42
 Bleeding
Yes
29
1.29
6
2.58
0.113
No
2220
98.71
227
97.42
 Seroma
Yes
51
2.27
14
6.01
<0.001
No
2198
97.73
219
93.99
 Infection
Yes
1
0.04
0
0.00
0.748
No
2248
99.96
233
100.0
 Bowell injury
Yes
1
0.04
0
0.00
0.748
No
2248
99.96
233
100.0
 Wound healing disorders
Yes
1
0.04
0
0.00
0.748
No
2248
99.96
233
100.0
Reoperations
Yes
27
1.20
6
2.58
0.081
No
2222
98.80
227
97.42
Recurrence on follow-up
Yes
28
1.24
8
3.43
0.008
No
2221
98.76
225
96.57
Pain in rest on follow-up
Yes
133
5.91
20
8.58
0.107
No
2116
94.09
213
91.42
Pain on exertion on follow-up
Yes
250
11.12
34
14.59
0.113
No
1999
88.88
199
85.41
Pain requiring treatment on follow-up
Yes
85
3.78
10
4.29
0.698
No
2164
96.22
223
95.71
For multivariable analysis of the intraoperative complications, complication-related reoperations and re-recurrences, it was not possible to calculate a valid model on differences of follow-up because of the small number of positive cases. On univariable analysis of pain at rest, pain on exertion and chronic pain requiring treatment, no difference was discerned for the procedures conducted in accordance with the guidelines.
The multivariable analysis results for the postoperative complications are presented in Table 13 (model matching: p < 0.001). The postoperative complications were impacted, in particular, by the procedures conducted in accordance with the guidelines (p = 0.001). When the guidelines were observed, the risk of onset of postoperative complications declined (OR 0.419 [0.248; 0.708]; p = 0.001). Besides, the defect size had a significant effect on the postoperative complication risk. Larger hernia defects (III vs I: OR 2.329 [1.135; 4.779]; p = 0.018) were associated with a higher complication risk.
Table 13
Multivariable analysis of postoperative complications in patients with laparo-endoscopic unilateral recurrent inguinal hernia repair
Parameter
p value
Category
OR estimate
95% CI
 
Guidelines
0.001
Yes versus no
0.419
0.248
0.708
Defect size
0.018
II (1.5–3 cm) versus I (<1.5 cm)
1.256
0.656
2.404
III (>3 cm) versus I (<1.5 cm)
2.329
1.135
4.779
Age (10-year OR)
0.089
 
1.152
0.979
1.357
EHS-classification medial
0.115
Yes versus no
0.572
0.285
1.146
Risk factor
0.269
Yes versus no
1.293
0.820
2.038
BMI (five-point OR)
0.420
 
0.876
0.634
1.210
EHS-classification femoral
0.429
Yes versus no
1.485
0.558
3.953
EHS-classification lateral
0.532
Yes versus no
0.797
0.392
1.621
EHS-classification scrotal
0.612
Yes versus no
1.378
0.399
4.758
ASA score
0.657
II versus I
0.849
0.484
1.489
III/IV versus I
1.056
0.512
2.179
3b.
How do the outcomes of open recurrent inguinal hernia repair differ on compliance versus non-compliance with the guidelines?
 
In the open recurrent repair group, only n = 897/2.320 (38.5%) of operations were performed following previous primary laparo-endoscopic inguinal hernia repair, i.e., according to the guidelines. Conduct of open recurrent repair following previous suture procedure for the primary inguinal hernia repair (n = 1.011/2.320; 43.4%) and after mesh procedure (n = 412/2.320; 17.7%) was not in compliance with the guidelines (Table 14). Below are now compared the open recurrent inguinal hernia repair procedures conducted on compliance (n = 897/2.320; 38.5%) versus non-compliance with the guidelines (n = 1.423/2.320; 61.3%).
Table 14
Open unilateral recurrent inguinal hernia repairs on compliance versus non-compliance with the guidelines
 
Previous operations
Total
Suture
Open mesh
Endoscopic mesh
N
ColPctN
N
ColPctN
N
ColPctN
N
ColPctN
Guidelines
 No
1011
100.0
412
100.0
1423
61.3
 Yes
897
100.0
897
38.7
 Total
1011
100.0
412
100.0
897
100.0
2320
100.0
Patients with recurrent inguinal hernias repaired in accordance with the guidelines had a significantly lower age and higher BMI (Table 15). Furthermore, patients operated on with an open procedure as per the guidelines had a significantly lower ASA score, smaller hernia defects, fewer risk factors and fewer lateral and scrotal hernias (Table 16). When the recurrent repair was performed as per the guidelines, open repair was associated with fewer postoperative complications (3.6 vs 5.8%; p = 0.021) and complication-related reoperation (1.0 vs 2.1%; p = 0.041) as well as a lower re-recurrence risk (1.1 vs 2.6%; p = 0.012). On the other hand, there was an increase in the risk of pain at rest (8.6 vs 5.4%; p = 0.003) and on exertion (15.0 vs 10.2%; p < 0.001; Table 17).
Table 15
Age and BMI of patients with open unilateral recurrent inguinal hernia repair on compliance versus non-compliance with the guidelines
 
Guidelines
p
Yes
No
Age (years)
Mean ± STD
59.3 ± 13.5
62.5 ± 16.2
<0.001
BMI
Mean ± STD
26.3 ± 3.6
25.8 ± 3.4
<0.001
Table 16
Demographic and surgery-related parameters and risk factors for patients with open unilateral recurrent inguinal hernia repair on compliance versus non-compliance with the guidelines
  
Guidelines
p
Yes
No
n
%
n
%
ASA score
I
258
28.45
368
25.86
<0.001
II
509
56.12
708
49.75
III/IV
140
15.44
347
24.39
Defect size
I (<1.5 cm)
154
16.98
240
16.87
0.028
II (1.5–3 cm)
498
54.91
711
49.96
III (>3 cm)
255
28.11
472
33.17
Risk factor
 Total
Yes
277
30.54
559
39.28
<0.001
No
630
69.46
864
60.72
 COPD
Yes
67
7.39
149
10.47
0.012
No
840
92.61
1274
89.53
 Diabetes
Yes
51
5.62
114
8.01
0.028
No
856
94.38
1309
91.99
 Aortic aneurism
Yes
4
0.44
11
0.77
0.329
No
903
99.56
1412
99.23
 Immunosuppression
Yes
10
1.10
23
1.62
0.306
No
897
98.90
1400
98.38
 Corticoid
Yes
8
0.88
29
2.04
0.030
No
899
99.12
1394
97.96
 Smoking
Yes
111
12.24
203
14.27
0.162
No
796
87.76
1220
85.73
 Coagulopathy
Yes
9
0.99
40
2.81
0.003
No
898
99.01
1383
97.19
 Antiplatelet medication
Yes
79
8.71
186
13.07
0.001
No
828
91.29
1237
86.93
 Anticoagulation therapy
Yes
25
2.76
50
3.51
0.313
No
882
97.24
1373
96.49
EHS-classification medial
Yes
523
57.66
795
55.87
0.394
No
384
42.34
628
44.13
EHS-classification lateral
Yes
460
50.72
800
56.22
0.009
No
447
49.28
623
43.78
EHS-classification femoral
Yes
15
1.65
32
2.25
0.319
No
892
98.35
1391
97.75
EHS-classification scrotal
Yes
12
1.32
63
4.43
<0.001
No
895
98.68
1360
95.57
Table 17
Intra- and postoperative complications, complication-related reoperations and 1-year follow-up results of patients with open unilateral recurrent inguinal hernia repair on compliance versus non-compliance with the guidelines
  
Yes
No
p
n
%
n
%
Intraoperative complication
 Total
Yes
14
1.54
23
1.62
0.891
No
893
98.46
1400
98.38
 Bleeding
Yes
3
0.33
12
0.84
0.131
No
904
99.67
1411
99.16
 Injury
  Total
Yes
12
1.32
14
0.98
0.447
No
895
98.68
1409
99.02
  Vascular
Yes
0
0.00
3
0.21
0.166
No
907
100.0
1420
99.79
  Bowell
Yes
0
0.00
4
0.28
0.110
No
907
100.0
1419
99.72
  Bladder
Yes
1
0.11
1
0.07
0.748
No
906
99.89
1422
99.93
  Nerve
Yes
9
0.99
1
0.07
<0.001
No
898
99.01
1422
99.93
Postoperative complication
 Total
Yes
33
3.64
82
5.76
0.021
No
874
96.36
1341
94.24
 Bleeding
Yes
17
1.87
45
3.16
0.060
No
890
98.13
1378
96.84
 Seroma
Yes
14
1.54
30
2.11
0.329
No
893
98.46
1393
97.89
 Infection
Yes
0
0.00
3
0.21
0.166
No
907
100.0
1420
99.79
 Wound healing disorders
Yes
4
0.44
7
0.49
0.861
No
903
99.56
1416
99.51
Reoperation
Yes
9
0.99
30
2.11
0.041
No
898
99.01
1393
97.89
Recurrence on follow-up
Yes
10
1.10
37
2.60
0.012
No
897
98.90
1386
97.40
Pain in rest on follow-up
Yes
78
8.60
77
5.41
0.003
No
829
91.40
1346
94.59
Pain on exertion on follow-up
Yes
136
14.99
145
10.19
<0.001
No
771
85.01
1278
89.81
Pain requiring treatment on follow-up
Yes
40
4.41
50
3.51
0.274
No
867
95.59
1373
96.49
For multivariable analysis of the intraoperative complications, complication-related reoperations and re-recurrences, it was not possible to calculate a valid model since the number of positive cases was too small. Univariable analysis of chronic pain requiring treatment did not detect any difference for repair as per the guidelines; therefore, no multivariable model was calculated.
The multivariable analysis results of variables influencing onset of postoperative complications are given in Table 18 (model matching: p = 0.002).
Table 18
Multivariable analysis of postoperative complications in patients with open unilateral recurrent inguinal hernia repair
Parameter
p value
Category
OR estimate
95% CI
Age (10-year OR)
0.003
 
1.275
1.085
1.498
Risk factor
0.118
Yes versus no
1.390
0.919
2.102
Guidelines
0.155
Yes versus no
0.734
0.479
1.124
EHS-classification lateral
0.165
Yes versus no
0.654
0.359
1.191
Defect size
0.181
II (1.5–3 cm) versus I (<1.5 cm)
0.718
0.420
1.225
III (>3 cm) versus I (<1.5 cm)
1.053
0.600
1.848
EHS-classification medial
0.225
Yes versus no
0.685
0.372
1.262
BMI (five-point OR)
0.392
 
0.880
0.656
1.180
ASA score
0.434
II versus I
0.742
0.439
1.256
III/IV versus I
0.913
0.470
1.775
EHS-classification femoral
0.935
Yes versus no
0.950
0.276
3.275
EHS-classification scrotal
0.975
Yes versus no
0.985
0.371
2.612
The postoperative complications were only affected by age, with older patients (10-year OR 1.275 [1.085; 1.498]; p = 0.003) having a higher risk of postoperative complications. There was no evidence that repair as per the guidelines impacted the postoperative complications.
The multivariable analysis results for pain at rest are presented in Table 19 (model matching: p < 0.001). Here, the hernia defect size proved to be the strongest influence factor (p = 0.006). A larger recurrent hernia (II vs I: OR 0.521 [0.346; 0.786]; III vs I: OR 0.560 [0.352; 0.892]) reduced the risk of pain at rest.
Table 19
Multivariable analysis of pain at rest in patients with open unilateral recurrent inguinal hernia repair
Parameter
p value
Category
OR estimate
95% CI
Defect size
0.006
II (1.5–3 cm) versus I (<1.5 cm)
0.521
0.346
0.786
III (>3 cm) versus I (<1.5 cm)
0.560
0.352
0.892
Guidelines
0.016
Yes versus no
1.508
1.079
2.107
BMI (five-point OR)
0.019
 
1.295
1.043
1.609
Age (10-year OR)
0.110
 
0.902
0.795
1.023
EHS-classification femoral
0.164
Yes versus no
0.238
0.032
1.798
EHS-classification lateral
0.243
Yes versus no
0.716
0.409
1.254
EHS-classification medial
0.352
Yes versus no
0.761
0.428
1.353
ASA score
0.490
II versus I
0.829
0.556
1.236
III/IV versus I
0.697
0.375
1.295
Risk factor
0.528
Yes versus no
1.126
0.779
1.628
EHS-classification scrotal
0.756
Yes versus no
0.839
0.276
2.545
Likewise, repair as per the guidelines (p = 0.016) and BMI (p = 0.019) had a significant influence on pain at rest. Repair as per the guidelines (OR 1.508 [1.079; 2.107]) as well as a five-point higher BMI (five-point OR 1.295 [1.043; 1.609]) increased the risk of pain at rest.
Another descriptive analysis revealed that the increased risk of pain at rest was attributed primarily to the small-sized (<1.5 cm) and medium-sized (1.5–3 cm) hernias (Table 20).
Table 20
Correlation of the defect size, compliance versus non-compliance with the guidelines and pain in rest on follow-up in patients with open unilateral recurrent inguinal hernia repair
  
Defect size
All
I (<1.5 cm)
II (1.5–3 cm)
III (>3 cm)
N
%
N
%
N
%
N
%
Guidelines
Pain in rest on follow-up
        
 No
No
217
90.4
685
96.3
444
94.1
1346
94.6
Yes
23
9.6
26
3.7
28
5.9
77
5.4
 Yes
No
135
87.7
455
91.4
239
93.7
829
91.4
Yes
19
12.3
43
8.6
16
6.3
78
8.6
The multivariable analysis results for pain on exertion are illustrated in Table 21 (model matching: p < 0.001). These were significantly influenced by the hernia defect size (p = 0.002), repair as per the guidelines (p = 0.010), BMI (p = 0.023), age (p = 0.027) and scrotal EHS classification (p = 0.036). A higher age (10-year OR 0.897 [0.814; 0.988]), larger hernias (II vs I: OR 0.654 [0.475; 0.901]; III vs I: OR 0.517 [0.335; 0.754]) as well as scrotal EHS classification (OR 0.211 [0.049; 0.900]) reduced the risk of pain on exertion. Conversely, there was a higher risk of pain for repair as per the guidelines (OR 1.401 [1.084; 1.810]) and for a five-point larger BMI (five-point OR 1.224 [1.029; 1.456]). Likewise, for pain on exertion the risk was attributable, in particular, to small-sized (<1.5 cm) and medium-sized (1.5–3 cm) recurrent hernias (Table 22).
Table 21
Multivariable analysis of pain on exertion in patients with open unilateral recurrent inguinal hernia repair
Parameter
p value
Category
OR estimate
95% CI
Defect size
0.002
II (1.5–3 cm) versus I (<1.5 cm)
0.654
0.475
0.901
III (>3 cm) versus I (<1.5 cm)
0.517
0.355
0.754
Guidelines
0.010
Yes versus no
1.401
1.084
1.810
BMI (five-point OR)
0.023
 
1.224
1.029
1.456
Age (10-year OR)
0.027
 
0.897
0.814
0.988
EHS-classification scrotal
0.036
Yes versus no
0.211
0.049
0.900
EHS-classification lateral
0.054
Yes versus no
0.653
0.423
1.007
Risk factor
0.241
Yes versus no
1.182
0.894
1.563
EHS-classification femoral
0.247
Yes versus no
0.531
0.182
1.551
EHS-classification medial
0.292
Yes versus no
0.787
0.504
1.229
ASA score
0.715
II versus I
1.054
0.769
1.446
III/IV versus I
0.905
0.563
1.453
Table 22
Correlation of the defect size, compliance versus non-compliance with the guidelines and pain on exertion on follow-up in patients with open unilateral recurrent inguinal hernia repair
 
Defect size
All
I (<1.5 cm)
II (1.5–3 cm)
III (>3 cm)
N
%
N
%
N
%
N
%
Guidelines
Pain on exertion on follow-up
        
 No
No
204
85.0
644
90.6
430
91.1
1278
89.8
Yes
36
15.0
67
9.4
42
8.9
145
10.2
 Yes
No
121
78.6
421
84.5
229
89.8
771
85.0
Yes
33
21.4
77
15.5
26
10.2
136
15.0

Discussion

1. The present analysis of data from the Herniamed Registry [29] first investigated to what extent participants in the Herniamed Hernia Registry [29] complied with the recommendations set out in the guidelines of the European Hernia Society (EHS). This revealed that laparo-endoscopic recurrent repair was used in 61.6% of cases following previous open suture repair and in 28.9% cases following open mesh repair as well as in 9.4% of cases following previous laparo-endoscopic operations. Hence, more than 90% of laparo-endoscopic recurrent repair procedures were performed in accordance with the EHS guidelines. Only 9.4% did not comply with the guidelines.
Matters were different for open recurrent repair. Only 38.5% of open recurrent repair operations were conducted following primary laparo-endoscopic repair. 43.4% of open recurrent repair procedures were performed following previous open suture repair and 17.7% following previous open mesh repair. As such, more than 60% of open recurrent operations did not comply with the recommendations of the guidelines. Already Richards et al. [13] and Richards and Earnshaw [28] pointed out that surgeons using predominantly open hernia surgery techniques also use predominantly open surgery for recurrent repair. It appears that the guidelines, which were first published in 2009 [23], have not changed that scenario. Further high-quality studies are needed to demonstrate that repair as per the guidelines really does achieve a better outcome for patients. Only when convincing evidence based on high-quality trials is available can greater acceptance of the guidelines be expected. Since to date no such studies have been carried out, it is no surprise that surgeons have called upon their own expertise when deciding on the surgical technique used to treat patients with recurrent inguinal hernia. Guidelines always only reflect the current state of knowledge gained from the studies reported in the scientific literature. If new published data are added, the recommendations may also change. Mere deviation from a guideline is unlikely to be considered as malpractice in litigation, unless the practice concerned is so well established that no responsible surgeon would fail to adhere to it [31].
2. To date, no study has compared the outcomes of recurrent inguinal hernia repair carried out in compliance with the guidelines. Therefore, the present analysis of Herniamed data [29] compared laparo-endoscopic with open recurrent repair performed as per the guidelines. No significant difference was identified between laparo-endoscopic and open techniques performed as per the guidelines in terms of the overall intraoperative complication rate, postoperative complication rate, complication-related reoperation rate, recurrence rate and rate of chronic pain requiring treatment. However, with regard to the intraoperative complications open recurrent repair was associated with significantly more nerve injuries as well as more pain at rest and pain on exertion on 1-year follow-up.
Multivariable analysis confirmed that laparo-endoscopic repair had a significant impact on pain at rest and pain on exertion, and was associated with a lower pain rate compared with open recurrent repair. Even on compliance with the guidelines, a significantly higher rate of pain at rest and pain on exertion must be expected when open repair is used following previous laparo-endoscopic operations compared with laparo-endoscopic repair after previous open repair. Therefore, such recurrent repair operations should be performed by surgeons who are highly experienced in the respective technique. Therefore, despite observance of the guidelines, higher rates of pain at rest and pain on exertion must be expected on using open recurrent repair following primary laparo-endoscopic repair than when using laparo-endoscopic recurrent repair following primary open repair.
3. In particular, since a large number of open (61.1%) and also a smaller number of laparo-endoscopic (9.4%) recurrent repair procedures were not performed in accordance with the recommendations of the guidelines, the question arises as to how the outcomes compare with the respective repair procedures carried out in compliance with the guidelines.
If recurrent repair is conducted as per the guidelines, laparo-endoscopic repair is associated with fewer intraoperative and postoperative complications and with a lower re-recurrence rate. No difference was found for the pain rates. Multivariable analysis demonstrated especially for the postoperative complications the impact of repair as per the guidelines.
Comparison of open recurrent repair conducted on compliance versus non-compliance with the guidelines revealed fewer postoperative complications and complication-related reoperation rates as well as a lower re-recurrence rate following repair as per the guidelines. On the other hand, the risk of pain at rest and on exertion was higher on compliance with the guidelines. Multivariable analysis revealed that the postoperative complications were only affected by age but not by the use of a repair procedure in accordance with the guidelines. Matters were different for pain at rest and pain on exertion. For the latter, multivariable analysis confirmed that repair as per the guidelines exerted a significantly negative effect on onset of pain at rest and pain on exertion. However, multivariable analysis as well as an additional analysis demonstrated that a small defect size had the greatest impact on the risk of pain at rest and pain on exertion. Likewise, a higher BMI negatively impacted the risk of pain at rest and pain on exertion. Although recommended in the guidelines, patients with a small defect size and a higher BMI have a higher risk of pain at rest and exertion following open repair of a recurrence after a previous laparo-endoscopic inguinal hernia repair. Therefore, sufficient diagnostic work-up of a small recurrence as cause of groin pain is mandatory.
In summary, it can be stated that in the Herniamed Registry (1) 90% of the laparo-endoscopic and only 40% of open recurrent inguinal hernia repair operations are carried out in accordance with the EHS guidelines; (2) comparison of laparo-endoscopic with open recurrent repair conducted in accordance with the guidelines demonstrated that open recurrent repair as per the guidelines was associated with a higher risk of pain at rest and pain on exertion on 1-year follow-up; and (3) finally, comparison of recurrent repair procedures on compliance versus non-compliance with the guidelines showed that both laparo-endoscopic and open repair operations that did not comply with the guidelines presented a higher risk of perioperative complications and re-recurrences. As such, the recommendations set out in the EHS guidelines should be implemented, but considering the specific circumstances of a given patient.

Acknowledgements

Ferdinand Köckerling has got grants to fund the Herniamed Registry from Johnson and Johnson, Norderstedt, Karl Storz, Tuttlingen, pfm medical, Cologne, Dahlhausen, Cologne, B Braun, Tuttlingen, MenkeMed, Munich, Bard, Karlsruhe and Resorba Medical GmbH, Nuremberg.

Herniamed Study Group

Scientific Board Köckerling, Ferdinand (Chairman) (Berlin); Bittner, Reinhard (Rottenburg); Fortelny, René (Wien); Jacob, Dietmar (Berlin); Koch, Andreas (Cottbus); Kraft, Barbara (Stuttgart); Kuthe, Andreas (Hannover); Lippert, Hans (Magdeburg): Lorenz, Ralph (Berlin); Mayer, Franz (Salzburg); Moesta, Kurt Thomas (Hannover); Niebuhr, Henning (Hamburg); Peiper, Christian (Hamm); Pross, Matthias (Berlin); Reinpold, Wolfgang (Hamburg); Simon, Thomas (Weinheim); Stechemesser, Bernd (Köln); Unger, Solveig (Chemnitz). Participants Ahmetov, Azat (Saint-Petersburg); Alapatt, Terence Francis (Frankfurt/Main); Albayrak, Nurettin (Herne); Amann, Stefan (Neuendettelsau); Anders, Stefan (Berlin); Anderson, Jürina (Würzburg); Antoine, Dirk (Leverkusen); Arndt, Anatoli (Elmshorn); Asperger, Walter (Halle); Avram, Iulian (Saarbrücken); Baikoglu-Endres, Corc (Weißenburg i. Bay.); Bandowsky, Boris (Damme); Barkus; Jörg (Velbert); Becker, Matthias (Freital); Behrend, Matthias (Deggendorf); Beuleke, Andrea (Burgwedel); Berger, Dieter (Baden-Baden); Birk, Dieter (Bietigheim-Bissingen); Bittner, Reinhard (Rottenburg); Blaha, Pavel (Zwiesel); Blumberg, Claus (Lübeck); Böckmann, Ulrich (Papenburg); Böhle, Arnd Steffen (Bremen); Bolle, Ludger (Berlin); Borchert, Erika (Grevenbroich); Born, Henry (Leipzig); Brabender, Jan (Köln); Breitenbuch von, Philipp (Radebeul); Brož, Miroslav (Ebersbach); Brütting, Alfred (Erlangen); Buchert, Annette (Mallersdorf-Pfaffenberg); Budzier, Eckhard (Meldorf); Burchett, Bert (Waren); Burghardt, Jens (Rüdersdorf); Cejnar, Stephan-Alexander (München); Chirikov, Ruslan (Dorsten); Claußnitzer, Christian (Ulm); Comman, Andreas (Bogen); Crescenti, Fabio (Verden/Aller); Daniels, Thies (Hamburg); Dapunt, Emanuela (Bruneck); Decker, Georg (Berlin); Demmel, Michael (Arnsberg); Descloux, Alexandre (Baden); Deusch, Klaus-Peter (Wiesbaden); Dick, Marcus (Neumünster); Dieterich, Klaus (Ditzingen); Dietz, Harald (Landshut); Dittmann, Michael (Northeim); Drummer, Bernhard (Forchheim); Eckermann, Oliver (Luckenwalde); Eckhoff, Jörn/Hamburg); Ehmann, Frank (Grünstadt); Eisenkrein, Alexander (Düren); Elger, Karlheinz (Germersheim); Engelhardt, Thomas (Erfurt); Erichsen, Axel (Friedrichshafen); Eucker, Dietmar (Bruderholz); Fackeldey, Volker (Kitzingen); Farke, Stefan (Delmenhorst); Faust, Hendrik (Emden); Federmann, Georg (Seehausen); Feichter, Albert (Wien); Fiedler, Michael (Eisenberg); Fikatas, Panagiotis (Berlin); Firl, Michaela (Perleberg); Fischer, Ines (Wiener Neustadt); Fleischer, Sabine (Dinslaken); Fortelny, René H. (Wien); Franczak, Andreas (Wien); Franke, Claus (Düsseldorf); Frankenberg von, Moritz (Salem); Frehner, Wolfgang (Ottobeuren); Friedhoff, Klaus (Andernach); Friedrich, Jürgen (Essen); Frings, Wolfram (Bonn); Fritsche, Ralf (Darmstadt); Frommhold, Klaus (Coesfeld); Frunder, Albrecht (Tübingen); Fuhrer, Günther (Reutlingen); Gassler, Harald (Villach); Gawad, Karim A. Frankfurt/Main); Gehrig, Tobias (Sinsheim); Gerdes, Martin (Ostercappeln); Germanov, German (Halberstadt; Gilg, Kai-Uwe (Hartmannsdorf); Glaubitz, Martin (Neumünster); Glauner-Goldschmidt, Kerstin (Werne); Glutig, Holger (Meissen); Gmeiner, Dietmar (Bad Dürrnberg); Göring, Herbert (München); Grebe, Werner (Rheda-Wiedenbrück); Grothe, Dirk (Melle); Gürtler, Thomas (Zürich); Hache, Helmer (Löbau); Hämmerle, Alexander (Bad Pyrmont); Haffner, Eugen (Hamm); Hain, Hans-Jürgen (Gross-Umstadt); Hammans, Sebastian (Lingen); Hampe, Carsten (Garbsen); Hanke, Stefan (Halle); Harrer, Petra (Starnberg); Hartung, Peter (Werne); Heinzmann, Bernd (Magdeburg); Heise, Joachim Wilfried (Stolberg); Heitland, Tim (München); Helbling, Christian (Rapperswil); Hempen, Hans-Günther (Cloppenburg); Henneking, Klaus-Wilhelm (Bayreuth); Hennes, Norbert (Duisburg); Hermes, Wolfgang (Weyhe); Herrgesell, Holger (Berlin); Herzing, Holger Höchstadt); Hessler, Christian (Bingen); Heuer, Matthias (Herten); Hildebrand, Christiaan (Langenfeld); Höferlin, Andreas (Mainz); Hoffmann, Henry (Basel); Hoffmann, Michael (Kassel); Hofmann, Eva M. (Frankfurt/Main); Hornung, Frederic (Wolfratshausen); Hügel, Omar (Hannover); Hüttemann, Martin (Oberhausen); Hunkeler, Rolf (Zürich); Imdahl, Andreas (Heidenheim); Isemer, Friedrich-Eckart (Wiesbaden); Jablonski, Herbert Gustav (Sögel); Jacob, Dietmar (Berlin); Jansen-Winkeln, Boris (Leipzig); Jantschulev, Methodi (Waren); Jenert, Burghard (Lichtenstein); Jugenheimer, Michael (Herrenberg); Junger, Marc (München); Kaaden, Stephan (Neustadt am Rübenberge); Käs, Stephan (Weiden); Kahraman, Orhan (Hamburg); Kaiser, Christian (Westerstede); Kaiser, Gernot Maximilian (Kamp-Lintfort); Kaiser, Stefan (Kleinmachnow); Kapischke, Matthias (Hamburg); Karch, Matthias (Eichstätt); Kasparek, Michael S. (München); Keck, Heinrich (Wolfenbüttel); Keller, Hans W. (Bonn); Kienzle, Ulrich (Karlsruhe); Kipfmüller, Brigitte (Köthen); Kirsch, Ulrike (Oranienburg); Klammer, Frank (Ahlen); Klatt, Richard (Hagen); Klein, Karl-Hermann (Burbach); Kleist, Sven (Berlin); Klobusicky, Pavol (Bad Kissingen); Kneifel, Thomas (Datteln); Knoop, Michael (Frankfurt/Oder); Knotter, Bianca (Mannheim); Koch, Andreas (Cottbus); Koch, Andreas (Münster); Köckerling, Ferdinand (Berlin); Köhler, Gernot (Linz); König, Oliver (Buchholz); Kornblum, Hans (Tübingen); Krämer, Dirk (Bad Zwischenahn); Kraft, Barbara (Stuttgart); Kratsch, Barthel (Dierdorf/Selters); Kreissl, Peter (Ebersberg); Krones, Carsten Johannes (Aachen); Kronhardt, Heinrich (Neustadt am Rübenberge); Kruse, Christinan (Aschaffenburg); Kube, Rainer (Cottbus); Kühlberg, Thomas (Berlin); Kühn, Gert (Freiberg); Kuhn, Roger (Gifhorn); Kusch, Eduard (Gütersloh); Kuthe, Andreas (Hannover); Ladberg, Ralf (Bremen); Ladra, Jürgen (Düren); Lahr-Eigen, Rolf (Potsdam); Lainka, Martin (Wattenscheid); Lammers, Bernhard J. (Neuss); Lancee, Steffen (Alsfeld); Lange, Claas (Berlin); Langer, Claus (Göttingen); Laps, Rainer (Ehringshausen); Larusson, Hannes Jon (Pinneberg); Lauschke, Holger (Duisburg); Leher, Markus (Schärding); Leidl, Stefan (Waidhofen/Ybbs); Lenz, Stefan (Berlin); Liedke, Marc Olaf (Heide); Lienert, Mark (Duisburg); Limberger, Andreas (Schrobenhausen); Limmer, Stefan (Würzburg); Locher, Martin (Kiel); Loghmanieh, Siawasch (Viersen); Lorenz, Ralph (Berlin); Luther, Stefan (Wipperfürth); Luyken, Walter (Sulzbach-Rosenberg); Mallmann, Bernhard (Krefeld); Manger, Regina (Schwabmünchen); Maurer, Stephan (Münster); May, Jens Peter (Schönebeck); Mayer, Franz (Salzburg); Mayer, Jens (Schwäbisch Gmünd); Mellert, Joachim (Höxter); Menzel, Ingo (Weimar); Meurer, Kirsten (Bochum); Meyer, Moritz (Ahaus); Mirow, Lutz (Kirchberg); Mittag-Bonsch, Martina (Crailsheim); Mittenzwey, Hans-Joachim (Berlin); Möbius, Ekkehard (Braunschweig); Mörder-Köttgen, Anja (Freiburg); Moesta, Kurt Thomas (Hannover); Moldenhauer, Ingolf (Braunschweig); Morkramer, Rolf (Xanten); Mosa, Tawfik (Merseburg); Müller, Hannes (Schlanders); Münzberg, Gregor (Berlin); Murr, Alfons (Vilshofen); Mussack, Thomas (St. Gallen); Nartschik, Peter (Quedlinburg); Nasifoglu, Bernd (Ehingen); Neumann, Jürgen (Haan); Neumeuer, Kai (Paderborn); Niebuhr, Henning (Hamburg); Nix, Carsten (Walsrode); Nölling, Anke (Burbach); Nostitz, Friedrich Zoltán (Mühlhausen); Obermaier, Straubing); Öz-Schmidt, Meryem (Hanau); Oldorf, Peter (Usingen); Olivieri, Manuel (Pforzheim); Passon, Marius (Freudenberg); Pawelzik, Marek (Hamburg); Pein, Tobias (Hameln); Peiper, Christian (Hamm); Peiper, Matthias (Essen); Peitgen, Klaus (Bottrop); Pertl, Alexander (Spittal/Drau); Philipp, Mark (Rostock); Pickart, Lutz (Bad Langensalza); Pizzera, Christian (Graz); Pöllath, Martin (Sulzbach-Rosenberg); Possin, Ulrich (Laatzen); Prenzel, Klaus (Bad Neuenahr-Ahrweiler); Pröve, Florian (Goslar); Pronnet, Thomas (Fürstenfeldbruck); Pross, Matthias (Berlin); Puff, Johannes (Dinkelsbühl); Rabl, Anton (Passau); Raggi, Matthias Claudius (Stuttgart); Rapp, Martin (Neunkirchen); Reck, Thomas (Püttlingen); Reinpold, Wolfgang (Hamburg); Reuter, Christoph (Quakenbrück); Richter, Jörg (Winnenden); Riemann, Kerstin (Alzenau-Wasserlos); Rodehorst, Anette (Otterndorf); Roehr, Thomas (Rödental); Rössler, Michael (Rüdesheim am Rhein); Roncossek, Bremerhaven); Rosniatowski, Rolland (Marburg); Roth Hartmut (Nürnberg); Sardoschau, Nihad (Saarbrücken); Sauer, Gottfried (Rüsselsheim); Sauer, Jörg (Arnsberg); Seekamp, Axel (Freiburg); Seelig, Matthias (Bad Soden); Seidel, Hanka (Eschweiler); Seiler, Christoph Michael (Warendorf); Seltmann, Cornelia (Hachenburg); Senkal, Metin (Witten); Shamiyeh, Andreas (Linz); Shang, Edward (München); Siemssen, Björn (Berlin); Sievers, Dörte (Hamburg); Silbernik, Daniel (Bonn); Simon, Thomas (Weinheim); Sinn, Daniel (Olpe); Sinner, Guy (Merzig); Sinning, Frank (Nürnberg); Smaxwil, Constatin Aurel (Stuttgart); Sörensen, Björn (Lauf an der Pegnitz); Syga, Günter (Bayreuth); Schabel, Volker (Kirchheim/Teck); Schadd, Peter (Euskirchen); Schassen von, Christian (Hamburg); Scheidbach, Hubert (Neustadt/Saale); Schelp, Lothar (Wuppertal); Scherf, Alexander (Pforzheim); Scheuerlein, Hubert (Paderborn); Scheyer, Mathias (Bludenz); Schilling, André (Kamen); Schimmelpenning, Hendrik (Neustadt in Holstein); Schinkel, Svenja (Kempten); Schmid, Michael (Gera); Schmid, Thomas (Innsbruck); Schmidt, Ulf (Mechernich); Schmitz, Heiner (Jena); Schmitz, Ronald (Altenburg); Schöche, Jan (Borna); Schoenen, Detlef (Schwandorf); Schrittwieser, Rudolf/Bruck an der Mur); Schroll, Andreas (München); Schubert, Daniel (Saarbrücken); Schüder, Gerhard (Wertheim); Schultz, Christian (Bremen-Lesum); Schultz, Harald (Landstuhl); Schulze, Frank P. Mülheim an der Ruhr); Schulze, Thomas (Dessau-Roßlau); Schumacher, Franz-Josef (Oberhausen); Schwab, Robert (Koblenz); Schwandner, Thilo (Lich); Schwarz, Jochen Günter (Rottenburg); Schymatzek, Ulrich (Eitorf); Spangenberger, Wolfgang (Bergisch-Gladbach); Sperling, Peter (Montabaur); Staade, Katja (Düsseldorf); Staib, Ludger (Esslingen); Staikov, Plamen (Frankfurt am Main); Stamm, Ingrid (Heppenheim); Stark, Wolfgang (Roth); Stechemesser, Bernd (Köln); Steinhilper, Uz (München); Stengl, Wolfgang (Nürnberg); Stern, Oliver (Hamburg); Stöltzing, Oliver (Meißen); Stolte, Thomas (Mannheim); Stopinski, Jürgen (Schwalmstadt); Stratmann, Gerald (Goch); Stubbe, Hendrik (Güstrow/); Stülzebach, Carsten (Friedrichroda); Tepel, Jürgen (Osnabrück); Terzić, Alexander (Wildeshausen); Teske, Ulrich (Essen); Tichomirow, Alexej (Brühl); Tillenburg, Wolfgang (Marktheidenfeld); Timmermann, Wolfgang (Hagen); Tomov, Tsvetomir (Koblenz; Train, Stefan H. (Gronau); Trauzettel, Uwe (Plettenberg); Triechelt, Uwe (Langenhagen); Ulbricht, Wolfgang (Breitenbrunn); Ulcar, Heimo (Schwarzach im Pongau); Unger, Solveig (Chemnitz); Verweel, Rainer (Hürth); Vogel, Ulrike (Berlin); Voigt, Rigo (Altenburg); Voit, Gerhard (Fürth); Volkers, Hans-Uwe (Norden); Volmer, Ulla (Berlin); Vossough, Alexander (Neuss); Wallasch, Andreas (Menden); Wallner, Axel (Lüdinghausen); Warscher, Manfred (Lienz); Warwas, Markus (Bonn); Weber, Jörg (Köln); Weber, Uwe (Eggenfelden); Weihrauch, Thomas (Ilmenau); Weiß, Johannes (Schwetzingen); Weißenbach, Peter (Neunkirchen); Werner, Uwe (Lübbecke-Rahden); Wessel, Ina (Duisburg); Weyhe, Dirk (Oldenburg); Wieber, Isabell (Köln); Wiesmann, Aloys (Rheine); Wiesner, Ingo (Halle); Withöft, Detlef (Neutraubling); Woehe, Fritz (Sanderhausen); Wolf, Claudio (Neuwied); Wolkersdörfer, Toralf (Pößneck); Yaksan, Arif (Wermeskirchen); Yildirim, Can (Lilienthal); Yildirim, Selcuk (Berlin); Zarras, Konstantinos (Düsseldorf); Zeller, Johannes (Waldshut-Tiengen); Zhorzel, Sven (Agatharied); Zuz, Gerhard (Leipzig).

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Disclosures

F. Köckerling, R. Bittner, A. Kuthe, B. Stechemesser, R. Lorenz, A. Koch, W. Reinpold, H. Niebuhr, M. Hukauf and C. Schug-Pass have no conflicts of interest or financial ties to disclose.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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