What are the influencing factors on the outcome in lateral incisional hernia repair? A registry-based multivariable analysis

Introduction Incisional hernias following lateral abdominal wall incisions with an incidence of 1–4% are less common than following medial incisions at 14–19%. The proportion of lateral incisional hernias in the total collective of all incisional hernias is around 17%. Compared to midline defects, lateral incisional hernias are more difficult to repair because of the more complex anatomy and localization. A recent systematic review identified only 11 publications with a total of 345 patients reporting on lateral incisional hernia repair. Therefore, further studies are urgently needed. Methods Multivariable analysis of the data available for 6,306 patients with primary elective lateral incisional hernia repair was performed to assess the confirmatory pre-defined potential influence factors and their association with the perioperative and one-year follow-up outcomes. Results In primary elective lateral incisional hernia repair, open onlay, open IPOM and suture procedures were found to have an unfavorable effect on the recurrence rate. This was also true for larger defect sizes and higher BMI. A particularly unfavorable relationship was identified between larger defect sizes and perioperative complications. Laparoscopic-IPOM presented a higher risk of intraoperative, and open sublay of postoperative, complications. The chronic pain rates were especially unfavorably influenced by the postoperative complications, preoperative pain and female gender. Conclusion Open-onlay, open IPOM and suture procedures, larger defect sizes, female gender, higher BMI, preoperative pain and postoperative complications are associated with unfavorable outcomes following primary elective lateral incisional hernia repair.

The proportion of lateral incisional hernias in the total collective of all incisional hernias is around 17% [5].
Compared with midline defects, lateral incisional hernias are more difficult to repair because of the more complex anatomy and localization [3]. With a lower caseload,   surgeons also generally lack the experience to repair lateral incisional hernias [3]. To date, there has also been a lack of guidelines for treatment of incisional hernias. An expert consensus guided by a systematic review contains no specific recommendations for treatment of lateral incisional hernias [6]. A systematic review collated the findings of 11 publications with a total of 345 patients following lateral incisional hernia repair [7]. Of these patients, only 27 (7.8%) underwent laparoscopic surgery. In these 11 studies the perioperative complication rates were 0-42%, recurrence rates 0-13% and the chronic pain rates 3-75% [7].
The authors conclude that the quality of the studies for repair of lateral incisional hernias is not sufficiently high to infer recommendations for everyday practice. Therefore, further studies are urgently needed for treatment of lateral incisional hernias.
The following analysis of data from the Herniamed Registry aims to analyze the influencing factors on the outcome of surgical repair of lateral incisional hernias.

Methods
Herniamed is an internet-based hernia registry in which hospitals and independent surgeons in Germany, Austria and Switzerland can voluntarily document their routine hernia operations [8,9]. The number of participating hospitals/surgical practices on 1 July 2021 was 816. All patients entered into the registry have signed a special consent form agreeing to their data being documented in the registry and to followup information being obtained after 1, 5 and 10 years. As part of the information provided to patients when giving informed consent to participate in the Herniamed Registry, they are also told that the treating hospital/ surgeon would like to be kept informed about any problem occurring after surgery. If problems or complications occur after the operation, the patient can at any time contact the treating hospital or treating surgeon to arrange for clinical examination. Perioperative complications are recorded for up to 30 days after surgery.
After 1, 5 and 10 years patients and their general practitioner are sent a questionnaire by the treating hospital or treating surgeon, enquiring once again about any postoperative complications.
In the questionnaire patients and their general practitioner are also asked about any pain at rest, pain on exertion or chronic pain requiring treatment. Patients and general practitioners are furthermore asked about any suspicious protrusion or recurrence.
If the patient or general practitioner reports chronic pain or suspected recurrence, the patient is invited by the treating hospital/surgeon for follow-up examination.
In the current analysis, the prospective data of patients who underwent primary elective lateral incisional hernia repair with the laparoscopic intraperitoneal onlay mesh (IPOM) technique or open suture, sublay, onlay or open IPOM approach were evaluated to assess all confirmatory pre-defined potential influencing factors on the perioperative and one-year follow-up outcome.
All analyses were performed with the software SAS 9.4 (SAS Institute Inc., Cary, NC, 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.
Individual outcome and influencing variables (risk factors, complications) are summarized as global variables. A general, intra-or postoperative complication or risk factor is deemed present if at least one single item applies.
Unadjusted analyses were performed to analyze the effect of an individual influencing variable on an outcome parameter, with the main focus on the association with the surgical procedure. For a categorical outcome variable the  chi-square test was used. For continuous outcome variables the ANOVA (analysis of variance) was used to analyze the influence of the comparison groups in, this case, four categories. The relation of confirmatory pre-defined patient and procedure-related characteristics to the outcome parameters (general, intraoperative and postoperative complications, complication-related reoperations, recurrences as well as pain at rest, pain on exertion and pain requiring treatment after one year) was assessed using a binary logistic regression model that permitted simultaneous evaluation of several influencing parameters. In addition, all pair-wise odds ratios are given with the corresponding 95% confidence interval. This quantifies how changes in an influencing variable affected the likelihood estimation of the outcome variables, with the other parameters seen as constant. For the continuous influencing variable age the 10-year odds ratio is given and for body mass index (BMI) a 5-point odds ratio. In

Unadjusted analysis
As seen in the patient inclusion flowchart (Fig. 1)  descriptive statistics as well as the test results for the continuous variables age and BMI and Table 2 the corresponding values for the categorical variables. Unadjusted analysis of the relationship between the surgical procedures and the patient-and diagnosis-related characteristics revealed that there were significant differences in all influencing variable scores. Table 3 shows unadjusted analysis of the relationship between the surgical procedures and the outcome variables. Depending on the surgical procedure, the rates of recurrence were 4.5-8.7%, pain at rest 9.7-13.8%, pain on exertion 17.1-22.7% and of chronic pain requiring treatment 7.5-11.7%. The perioperative complications rates were 7.7-9.9%.

Intraoperative complications
The results of the model used for analysis of the association between the patient-and procedure-related characteristics with the occurrence of intraoperative complications are illustrated in Table 4 (model fit: p < 0.001). The risk of onset of intraoperative complications was significantly associated with the surgical procedures (p < 0.001), use of a drain (p = 0.003) and the defect size (p = 0.036) (  Fig. 2).
Intraoperative complications were less common in the open onlay than in the suture procedure (Table 4, Fig. 2). Larger defect sizes were also associated with a higher risk of intraoperative complications (Table 4, Fig. 3). Likewise, intraoperative complications were associated with a significantly more frequent use of drains (Table 4).

Postoperative complications
The results of the model used for analysis of the relation of the patient-and procedure-related characteristics to the risk of postoperative complications are shown in Table 5 (model fit: p < 0.001). Postoperative complications were significantly associated with the defect size (p < 0.001) and BMI (p = 0.002) ( Table 5, Fig. 3). There was no global significant relation between the surgical procedure and the occurrence of postoperative complications (p = 0.153). Only in pair-wise comparisons the open sublay procedure compared with the laparoscopic IPOM was associated with a higher risk of postoperative complications (Table 5, Fig. 3).

Complication-related reoperations
The analysis results of the complication-related reoperations are presented in Table 6 (model fit: p < 0.001). The increased risk of a complication-related reoperation was significantly associated with the defect size (p = 0.002) and with the use of a drain (p = 0.032) ( Table 6, Fig. 3).

General complications
The results of (the model used for) analysis of the influence exerted by the patient-and procedure-related characteristics on the risk of general complications are illustrated in Table 7 (model fit: p < 0.001). The general complications were significantly associated with the defect size (p < 0.001), ASA score (p = 0.002) and the use of drains (p = 0.012) ( Table  7, Fig. 3).

Recurrence
The multivariable analysis results of the influencing factors on the onset of recurrences at one-year follow-up are  Fig. 2). The open sublay procedure posed a lower risk of recurrence than the open onlay procedure (Table 8, Fig. 2).

Pain at rest
The multivariable analysis results of the influencing factors on pain at rest at one-year follow-up are illustrated In Table  9 (model fit: p < 0.001).
A lower risk of pain at rest at one-year follow-up was found in higher age (p < 0.001) (Table 9, Fig. 3). Preoperative pain (p < 0.001), postoperative complications (p < 0.001), female gender (p = 0.007) and higher ASA score presented a higher risk of pain at rest (p = 0.007) ( Table 9, Fig. 3). Surgical procedures tended to be associated with at rest (p = 0.076).
In detail, only the open suture procedure compared with  laparoscopic and open IPOM, open onlay and open sublay  presented a lower pain risk (Table 9, Fig. 2).

Pain on exertion
The multivariable analysis results of pain on exertion at oneyear follow-up are shown in Table 10 (model fit: p < 0.001).
Higher age was associated with a lower risk of pain on exertion (p < 0.001). Preoperative pain (p < 0.001), female gender (p < 0.001), larger defect size (p = 0.004) and postoperative complications (p = 0.040) were associated with a significantly higher rate of pain on exertion (Table 10, Fig. 3).

Chronic pain requiring treatment
The multivariable analysis results of the influencing factors on chronic pain requiring treatment following lateral incisional hernia repair are illustrated in Table 11 (model fit: p < 0.001). Here, too, a lower risk was identified in higher age (p < 0.001). Likewise, preoperative pain (p < 0.001), postoperative complications (p = 0.002) and female gender (p < 0.001) were found to present a significantly higher risk of chronic pain requiring treatment (Table11, Fig. 3). This was also true for higher ASA score (p = 0.003).

Discussion
The most important study so far on the treatment of lateral incisional hernia is the review by Zhou et al. [7] which included 11 publications with a total of 345 lateral incisional hernia repairs. That review reported on the perioperative complication rates and findings after 4-60 months' followup. In the Herniamed analysis presented here all patients were followed up for one year.
Whereas the rate of laparoscopic operations in the review was only 7.8%, in the Herniamed Registry it was 27.1%. It is not possible to give a more precise description of the open surgical procedures used in the review, but the predominant procedure was the open retromuscular/sublay procedure [7]. In the Herniamed Registry, too, the open retromuscular/sublay procedure at 38.9% was the most commonly used surgical procedure.
The unadjusted analysis results for the different surgical procedures revealed for the Herniamed cohort recurrence rates of 4.5-8.7% and for pain on exertion 17.1-22.7%. As such, the unadjusted results for the various surgical procedures are in the same range reported in the review. In the review no further analysis was carried out to identify the influence exerted by the choice of surgical procedure and the presence of other potentially influencing factors on the outcome of lateral incisional hernia repair (Fig. 4).
The intraoperative complication rate was highly significantly or significantly unfavorably associated with the laparoscopic and open IPOM, open suture procedure and larger defect sizes.
The postoperative complication rate revealed a very unfavorable or unfavorable relation to the open retromuscular/ sublay procedure, larger defect size and higher BMI. The complication-related reoperation rate was associated unfavorably or very unfavorably only with larger defect sizes.
The general complications were found to have a very unfavorable relationship with defect sizes > 10 cm and an unfavorable association with higher ASA score.
The recurrence rate was significantly or highly significantly unfavorably related to the open onlay surgical procedure, suture procedure and open IPOM as well as by larger defect sizes and higher BMI.
The rates of pain on exertion and chronic pain requiring treatment were not significantly related to the surgical procedures. Only for pain at rest was a significantly more favorable association identified for the use of the suture procedure. A highly significantly or significantly unfavorable relation was found between the pain rates and defect sizes, female gender, higher ASA score, preoperative pain and postoperative complications. Higher age had a significantly favorable association with the pain rates.
It can thus be concluded that for the choice of surgical procedure in lateral incisional hernia repair the risk of chronic pain tends to be of lesser importance. Chronic pain was found to be significantly more unfavorably related to larger defect sizes, younger age, female gender, higher ASA Hence, in terms of recurrence rate the more favorable outcomes were identified for the laparoscopic IPOM procedure and the open retromuscular/sublay procedure. Therefore, the defect size and BMI, which had a significant to highly significant relation to the recurrence rate, must also be taken into account. Furthermore, the laparoscopic IPOM presented a higher risk of intraoperative complications and the open retromuscular/sublay procedure of postoperative complications. Hence, it appears that the ideal surgical procedure for lateral incisional hernias has not been identified so far. Intraperitoneal mesh placement has been the subject of increasing controversial debate in recent years because of potential complications [10]. Therefore, there has been a sharp decline in number of laparoscopic IPOM procedures for treatment of incisional hernias [11]. This has led to an increase in the use of the open retromuscular/ sublay procedure, which is associated with a significantly higher rate of perioperative complication rates [11]. The future alternative to the laparoscopic IPOM and open retromuscular/sublay procedure for repair of lateral incisional hernias is likely to be laparo-endoscopic or robotic transversus abdominis release procedures or hybrid techniques [12][13][14][15][16]. Initial, promising results are available for the procedures. The results must be measured against those presented here for the established surgical procedures.
Of course, results based on registry data bear some risk of bias and are potentially hampered by missing or incorrect data [5]. Thus, all responsible surgeons participating in the Herniamed Registry sign a contract for data correctness and completeness [5]. The Registry software will flag up any missing data. At one-year follow-up postoperative complications are queried once again. On certification of hernia centers the experts can check the data for completion and correctness. The lack of follow-ups (drop-out) for a relevant proportion is another limitation of the registry, but the subgroup analysis does not show any selection bias. In summary, it can be stated that the open onlay, open IPOM and suture procedures have an unfavorable relation to the recurrence rate. Hence, for repair of primary lateral incisional hernias preference should be given to the laparoscopic IPOM and the open sublay procedure. As regards the risk of chronic pain no significant difference has been identified between the procedures. The laparoscopic IPOM is associated with a higher risk of intraoperative, and the open sublay procedure of postoperative, complications. Larger defect sizes are found to have the most unfavorable association with the perioperative complication rates and recurrence rates. The most unfavorable relationship with chronic pain is seen for postoperative complications, female gender and preoperative pain. Higher age has a favorable association with chronic pain.
Funding Open Access funding enabled and organized by Projekt DEAL. This study received no funding.   informed consent declaration agreeing to participate. The Herniamed Registry has ethical approval (BASEC Nr 2016-00123, 287/2017BO2).

Human and animal rights
This article does not contain any study with animals performed by any of the authors.
Informed consent All patients with routine hernia surgery documented in the Herniamed Registry have signed an informed consent declaration agreeing to participate.
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