MD Fabrizio Panaro
email: f-panaro@chu-montpellier.fr

MD Piera Leon

MD Thierry Perniceni

MD Giorgio Bianchi

MD Francois-Regis Souche

MD, PhD Jean Michel Fabre

MD, PhD Vito De Blasi

MD Santiago Azagra

; Grégory

MD Giusy Gianandrea

MD, PhD Brice Gayet

MD, PhD Francis Navarro

MD, PhD David Fuks

Laparoscopic repeat surgery for gastro-oesophageal reflux disease: results of the analyses of a cohort study of 117 patients from a multicenter experience Running title: Repeat surgery for GERD

Keywords: Gastroesophageal reflux disease, recurrence, minimal invasive surgery, repeat surgery

Background: Short and long-term outcomes after repeat anti-reflux surgery (RARS) are still debated and generally not considered as satisfying as after primary anti-reflux surgery (PARS). The aim of this study was to evaluate functional outcomes after RARS and risk factors associated to intra-operative and post-operative complications.

Methods

: This is a multicenter retrospective survey from four European laparoscopic centers. Patients who underwent elective RARS from January 2005 to October 2017 for dysphagia or for persistent reflux disease refractory to medical treatment were analyzed. Data on demographic characteristics, including type and timing of previous operations as well as intra-operative details (surgical technique, type of RARS, conversion to open surgery, prosthetic material placement) were collected. Patients who underwent operations in the emergency setting, interventions mixed with bariatric procedures and PARS performed in other surgical departments were not included in this study. Primary endpoint of this study was to evaluate risk factors associated with intraoperative and postoperative complications. Secondary endpoint was to evaluate clinical outcomes and to identify any possible correlation with clinical and surgical parameters.

Conclusions: Repeat anti-reflux surgery is a safe and feasible procedure in high-volume centers, with acceptable perioperative outcomes. Long-term results are favorable with a success rate of almost 80%.

Advanced age (> 70 years) and low BMI (<23 kg/m 2 ) were factor predicting perioperative complications. The use of prosthesis for hiatoplasty was associated to better functional outcomes.

Results: Among 1662 patients who underwent PARS, failure occurred in 174 (10.5%) patients.

Repeat surgery was performed in 117 (7%) patients, after a mean time of 80 months (range 4-315).

RARS was carried out laparoscopically in 88% of cases. Prosthetic mesh to reinforce hiatoplasty was used in 22.2% of patients. Intra-operative upper gastro-intestinal tract's injuries occurred in 6 (5.1%) patients. Perioperative mortality was nil and 13 (11.1%) patients experienced postoperative complications. Mean length of hospital stay was 9.6±6.4 days. Based on a multivariable analysis, age >70 years (OR 1.074, C.I.95% 1.018-1.133, p=0.008) and body mass index (BMI) <23 (OR 0.172, C.I.95% 0.052-0.568, p=0.004) were independently associated to postoperative complications. After a mean follow-up time of 36 months (range 6-107), 24 (20.5%) patients presented recurrent symptoms.

Based on a multivariable analysis, early onset of dysphagia (OR 3.539, C.I.95% 1.254-9.990, p=0.017), open approach (OR 4.505, C.I.95% 1.314-15.442, p=0.016) and the use of prosthetic material (OR 2.790, C.I.95% 0.930 -8.776, p=0.047) were significantly associated to good clinical outcomes.

INTRODUCTION

The incidence of reflux disease resistant to proton pumps inhibitors has widely raised, especially in Western Countries and in East Asia, leading to an increased number of patients undergoing anti-reflux surgery [START_REF] El-Serag | Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review[END_REF] . Among patients having a primary anti-reflux surgery (PARS), at least 2% to 30% develop a recurrence of symptoms, with an important deterioration of their quality of life [START_REF] Smith | When Fundoplication Fails: Redo?[END_REF][START_REF] Maret-Ouda | Association Between Laparoscopic Antireflux Surgery and Recurrence of Gastroesophageal Reflux[END_REF] .

Hiatal failure, incorrect wrap construction or wrap disruption as well as wrap slippage are considered the most common causes of failure after PARS [START_REF] Horgan | Failed antireflux surgery: what have we learned from reoperations?[END_REF][START_REF] Celasin H 1 | Laparoscopic revision surgery for gastroesophageal reflux disease[END_REF][START_REF] Patti | Analysis of the Causes of Failed Antireflux Surgery and the Principles of Treatment: A Review[END_REF] .

As high as 3 to 10% of patients require a repeat anti-reflux surgery (RARS) [START_REF] Makdisi | Laparoscopic Repair for Failed Antireflux Procedures[END_REF] .

Actually, long-term outcomes after RARS are not well established. Some series reported less impressive outcomes after RARS than after PARS [START_REF] Dallemagne | Long-term results after laparoscopic reoperation for failed antireflux procedures[END_REF][START_REF] Meester | Nissen fundoplication for gastroesophageal reflux disease. Evaluation of primary repair in 100 consecutive patients[END_REF][START_REF] Awais | Reoperative Antireflux Surgery for Failed Fundoplication: An Analysis of Outcomes in 275 Patients[END_REF] . The rate of success after RARS is 85-90% while stands at 90-95% after PARS [START_REF] Meester | Nissen fundoplication for gastroesophageal reflux disease. Evaluation of primary repair in 100 consecutive patients[END_REF][START_REF] Awais | Reoperative Antireflux Surgery for Failed Fundoplication: An Analysis of Outcomes in 275 Patients[END_REF] . Recurrent symptoms occur in 2 to 30% of patients after redo surgery [START_REF] Dallemagne | Long-term results after laparoscopic reoperation for failed antireflux procedures[END_REF] . Furthermore, intraoperative complications such as upper gastro-intestinal tract's injuries are generally considered to be more frequent in RARS (0-38%), probably in relation to the alteration of the normal anatomy of the hiatus and tissue consistency [START_REF] Byrne | Symptomatic and functional outcome after laparoscopic reoperation for failed antireflux surgery[END_REF][START_REF] Furnée | Surgical Reintervention after Failed Antireflux Surgery: A Systematic Review of the Literature[END_REF] . Nevertheless, there are few studies that evaluated both short-and long-term outcomes after RARS in a large multicentre setting [START_REF] Byrne | Symptomatic and functional outcome after laparoscopic reoperation for failed antireflux surgery[END_REF] .

The aim of our study was to evaluate the risk factors associated to postoperative complications and to poor clinical outcomes after RARS in a large multicentre cohort.

MATERIALS and METHODS

Patient selection

All patients who underwent elective RARS for persistent reflux disease under medical treatment or intolerance to medical therapy from January 2005 to October 2017, were retrospectively reviewed from a prospectively collected database from four European Centers.

The four Surgical Departments concerned were tertiary centers performing more than 50 gastroesophageal procedures/year. The two surgical divisions of the University Hospital of Montpellier, as well as the CHL of Luxembourg and the Institut Mutualiste Montsouris in Paris provided the data.

Patients who underwent operations in the emergency setting, interventions mixed with bariatric procedures and PARS performed in other surgical departments were excluded from this survey. This study was approved by the Institutional Review Board (IRB, #2018-07-0186) and it was aligned to Helsinky declaration.

Preoperative evaluation and investigations

Poor clinical outcome that justified RARS was defined by the recurrence of reflux symptoms (heartburn, regurgitation and/or chest pain) or by the development of dysphagia with or without recurrent hiatal hernia after PARS.

All patients undergoing RARS underwent a comprehensive history and physical exam. A detailed assess of previous operations was performed. Barium contrast radiography of the upper gastrointestinal tract and oesophago-gastroscopy were systematically conducted. Esophageal manometry and pH testing were performed as (87%) of patients.

Data on demographic features, BMI, ASA, symptoms, type and time of previous operations were collected.

Operative technique

All four centers adopted a roughly standardized surgical technique for both PARS and RARS. The primary surgical approach was generally mini-invasive. The RARS surgery was carried out by a senior surgeon with a minimum experience of 50 procedures annually. In brief, at RARS, the patient was placed in the standard French position, with a reverse Trendelenburg. A standard five-port technique was routinely used. The first step of the surgical exploration was focused on identifying the potential cause of failure. The second step was about re-performing the anti-reflux surgery. Otherwise, fundoplication and hiatoplasty were generally disassembled, paying attention to avoid either digestive or vagal injury. In patients presenting with severe dysphagia and no wrap herniation, the main target was to reconstruct a floppier fundoplication. In particular, the Toupet valve (270°) was the most frequently type of fundoplication performed.

In case of partial or complete hiatal herniation, the hiatus was reconstructed and a wrap was performed as well. An intraperitoneal non-absorbable prosthetic mesh was placed only in case of important hiatal defects (>5 cm) not suitable for tension-free closure.

When a wrap disruption was intraoperatively detected, an anti-reflux fundoplication was provided.

In cases of conversion to the open technique, a midline incision was performed.

At the end of the operation, an intra-abdominal drainage was placed when dissection was traumatic with significant bleeding and in case of hollow organ injuries detected and immediately repaired. Surgical approach, surgical technique, conversion to open surgery and its cause, use of prosthetic material and drainage placement were included in this study and referred as intraoperative data.

Follow up and data collection

Postoperative complications were assessed as well and graded according to Clavien-Dindo classification [START_REF] Dindo | Classification of Surgical Complications: A New Proposal With valuation in a Cohort of 6336 Patients and Results of a Survey[END_REF] . Severe postoperative complications were defined as Clavien-Dindo ≥ 3.

Patients were then re-evaluated after one, six and twelve months from RARS. Radiologic (CT-scan) and endoscopic exams were systematically planned during surveillance.

WHO quality of life after surgery was assessed. It was defined by scores of six broad domains of quality of life (the physical domain, the psychological one, independence level, social relationships, environment and spirituality/religion/personal beliefs) and was graded on a 1 to 6 scale (1=very poor, 2= poor, 3= neither poor nor good, 4= good, 5= very good, 6= not known) [START_REF] Skevington | The World Health Organization's WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A report from the WHOQOL group[END_REF] .

Early failure was defined as recurrence of reflux symptoms or the occurrence of grade ≥ 4 dysphagia one month after surgery.

GERD recurrence was defined by the presence of typical reflux symptoms as retrosternal burning, often labeled heartburn, regurgitation, and epigastric pain with or without sleep disturbance [START_REF] Vakil | The Montreal definition and classification of gastro-esophageal reflux disease: a global evidence-based consensus paper[END_REF] . Patient presenting early failure underwent CT scan and systematic manometry and pH monitoring.

When detected on imaging, recurrent hiatal herniation included partial or full herniation of the wrap into the mediastinum and partial or complete wrap disruption. Partial wrap disruption was identified when the anterior fundal apposition was attenuated or partly separated, completed wrap break-down was defined when the wrap was no longer visible [START_REF] Koetje | Measuring outcomes of laparoscopic anti-reflux surgery: quality of life versus symptom scores?[END_REF] .

Outcomes

Primary endpoint of this study was to evaluate complication rate and risk factors associated to intraoperative and postoperative complications. Secondary endpoint was to evaluate clinical outcomes and to identify any possible correlation with clinical and surgical parameters.

Statistical analysis

All statistical analyses were conducted by the Department of the Statistical Analysis Unit of the University of Montpellier using GraphPad Prism® and R software®. Descriptive data were expressed as the mean ± standard deviation. Categorical variables and proportions were compared using the Chisquared test or the Fisher exact test. Logistic regression modeling was performed to identify significant variables to predict failure. The univariate analysis was performed using a logistic regression model where the predicted variables were the outcomes of the surgery in terms of persistence of symptoms (symptomatic versus asymptomatic) and the presence of complications. The variables which were found to have a p-value <0.15 on univariate analysis were further analyzed using a multivariate logistic model.

RESULTS

Patient characteristics

Among 1662 patients who underwent PARS (laparoscopically performed in 96.6% of cases), surgical failure occurred in 174 (10.5%) patients, after a mean time of 80 months (range 4-315).

However, RARS was performed in only 117 (7%) patients, mainly for GERD symptom recurrence (70 patients, 59.8%), confirmed by pH monitoring. Mean time between diagnosis of failure after PARS and RARS was 22 months.

In this cohort study of 117 patients, the female/male ratio was 1.54 (71/46), the mean age was 60.4 years (range 17-89 years) and the mean body mass index (BMI) was 25.5 (range 17-35). As detailed in Table 1, patients were mostly ASA (American Society of Anaesthesiologists classification) II at the time of operation.

Surgical RARS procedures

Laparoscopic RARS was carried out in 103 patients out of 117 (88% of cases). An early conversion to the open technique (midline incision) was performed in 14 patients (12%), due to the presence of strong adhesions in the hiatal region. The most common intra-operative finding was hiatal hernia recurrence, observed in 87 (74.3%) patients.

Fundoplication sequence of reconstruction in RARS followed the principle of anatomical feasibility and preoperative clinical presentation (GERD or dysphagia i.e.). A Nissen fundoplication was reperformed in (16) 13.6% of patients after a previous Nissen fundoplication, a Toupet fundoplication after a Nissen procedure in (61) 52.1%, a Nissen fundoplication after a Toupet procedure in (6) 5.1% and a Toupet fundoplication after a Toupet fundoplication in (23) 19.6% of the cases. In 11 out of 117 patients (9.4%) this data in not available.

The prosthetic mesh for hiatoplasty reinforcement was used in (26 out of 117 patients, 22.2%) of the cases and an intra-abdominal drainage was provided in 61 (52.1%) patients.

No oesophageal lengthening procedures such Collis'one were required as the mobilisation of the intrathoracic oesophagus was systematically obtained.

Intra-operative upper gastro-intestinal tract's injuries (immediately recognized and repaired in our experience) occurred in 6 (5.1%) patients. We accounted for one case of oesophageal perforation, five cases of gastric perforation and one case of partial spleen laceration.

Postoperative complications

Postoperative mortality was nil and 13 (11.1%) patients experienced postoperative complications. Six (5.1%) patients developed postoperative respiratory impairment due to atelectasis, pleural effusion or pneumothorax. One patient experienced postoperative mild cardiac failure but did not require ICU admission. The highest Clavien-Dindo score reported for postoperative complications was graded II.

Mean length of hospital stay was 9.6 ± 6.42 days, the longest one lasted 41 days. Length of hospital stay was significantly longer in patients who developed postoperative complications (14 ± 11.2 vs 5.25 ± 1.6 days, p=0.0001). Elderly patients (>70 years-old) experienced more frequently postoperative complications compared to their younger counterparts (mean age of 74 years in complicated patients versus 61 years in patients with no complication, p=0.015).

Risk factors for postoperative complications are detailed in the analyses reported in Tables 2 and3.

Based on a multivariable analysis

Functional outcomes

After a mean follow-up time of 36 months (range 6-107), the overall success rate after RARS was 79.5% (93 patients out of 117). Twenty-four (20.5%) patients presented postoperative onset of recurrent symptoms significantly impacting their quality of life. Eleven patients (9.4%) presented recurrent GERD symptoms in the early postoperative period and ten of them still presented GERD beyond the first year after RARS. Moreover, 13 patients (11.1%) presented early post-operative highgrade dysphagia but only two of them presented persisting high-grade dysphagia beyond the first year after RARS.

The analysis of the WHO QoL questionnaire applied after RARS revealed a mean value of 3.65 ± 1.35. Postoperative complications did not affect QoL.

On univariate analysis, the early onset of high-grade dysphagia, open surgical approach and use of prosthetic material positively influenced clinical outcomes (see results in Table 4). Based on a multivariable analysis, early dysphagia onset (OR 3.539, C.I.95% 1.254-9.990, p=0.017), open surgical approach (OR 4.505, C.I.95% 1.314-15.442, p=0.016) and use of prosthetic material in order to reconstruct the hiatus (OR: 2.790, C.I.95% 1.039-8.776, p=0.047) were confirmed as factors significantly associated to better clinical outcomes (Table 5).

DISCUSSION

In the present study, surgical failure after PARS occurred in 10.5% of the cases. After a mean followup time of almost seven years, RARS was finally performed in 117 (7%) out of 1662 patients, with an acceptable morbidity rate of 11.1% and a success rate of almost 80%.

Repeat surgery for recurrent reflux disease is still a challenging issue. Compared to PARS [START_REF] Patti | Recurrence of Reflux After Laparoscopic Antireflux Surgery[END_REF][START_REF] Schlottmann | Surgery for benign esophageal disorders in the US: risk factors for complications and trends of morbidity[END_REF] , which is carried out mostly using the laparoscopic approach with a satisfactory success rate and limited morbidity, postoperative outcomes after RARS may be poor [START_REF] Rosemurgy | Reoperative fundoplications are effective treatment for dysphagia and recurrent gastroesophageal reflux[END_REF] . Indeed, conversion rate, morbidity and mortality rates seem to be slightly increased in RARS. Moreover, functional outcomes after repeat surgery are not always as satisfying as after PARS [START_REF] Frantzides | Laparoscopic Revision of Failed Fundoplication and Hiatal Herniorraphy[END_REF][START_REF] Furnée | Surgical Reintervention After Failed Antireflux Surgery: A Systematic Review of the Literature[END_REF][START_REF] Floch | Is Laparoscopic Reoperation for Failed Antireflux Surgery Feasible?[END_REF] . Failure after PARS is mainly due to hiatal hernia recurrence and this situation may be attributed to an incomplete mobilization of the intrathoracic esophagus, to wrap disruption or even to inadequate repair of the hiatus [START_REF] Patti | Analysis of the Causes of Failed Antireflux Surgery and the Principles of Treatment: A Review[END_REF][START_REF] Frantzides | Laparoscopic Revision of Failed Fundoplication and Hiatal Herniorraphy[END_REF] . In the present series, the most frequent intra-operative finding was hiatal hernia recurrence (75% of cases).

Including more than one hundred RARS, the present series represents a large multicenter reporting of patients undergone repeat surgery for reflux recurrence after failure of a primary procedure. Digestive perforations occurred in 5.1% of the cases, they were all intraoperatively detected and repaired. Postoperative mortality was nil and morbidity remains limited to less than 15%, in accordance with literature [START_REF] Serafini | Laparoscopic revision of failed antireflux operations[END_REF] .

In the present series, elderly patients (>70 years) and BMI less than 23 were significantly associated to an increased risk of peri-operative complications. Patients' age has been already identified as a risk factor for postoperative complications [START_REF] Awais | Roux-en-Y gastric bypass of intractable gastroesophageal reflux after antireflux surgery[END_REF] .

Interestingly, a BMI higher than 23 was associated to lower rate of post-operative complications, raising questions on the potential protective role of intra-abdominal fat around the hiatus that may reduce local inflammatory response [START_REF] Kott | The BMI paradox and robotic assisted partial nephrectomy[END_REF] .

According to the existing data [START_REF] Patti | Analysis of the Causes of Failed Antireflux Surgery and the Principles of Treatment: A Review[END_REF][START_REF] Frantzides | Laparoscopic Revision of Failed Fundoplication and Hiatal Herniorraphy[END_REF][START_REF] Furnée | Surgical Reintervention After Failed Antireflux Surgery: A Systematic Review of the Literature[END_REF][START_REF] Floch | Is Laparoscopic Reoperation for Failed Antireflux Surgery Feasible?[END_REF] , failure after laparoscopic or open PARS occurs in as high as 15% of the patients, even in highly specialized centers. In order to achieve a better knowledge of the evolution of this disease and to assess the real failure rate, the follow-up should be extensively protracted. The mean follow-up time of the present study is 36 months and failure rate accounted for 20.5%. Notably, early onset of dysphagia gradually regressed over time. Surprisingly, this transient postoperative dysphagia was associated to a positive impact on functional clinical outcomes.

Similarly, Granderath et al. [START_REF] Granderath | Failed antireflux surgery: quality of life and surgical outcome after laparoscopic refundoplication[END_REF] reported a 3-fold (12%) incidence of symptomatic dysphagia at 3 months in patients with prosthetic mesh compared to those who underwent just sutured hiatoplasty. However, the rate of symptomatic dysphagia was 4% in each group one year after surgery. Nevertheless, the herniation rate recurrence was in favor of the use of mesh (26% in the 'no mesh' group versus 5% in the 'mesh' group, p<0.001).

Although the early onset of dysphagia, the present study confirms that placement of prosthetic mesh, positively influenced clinical outcomes after RARS at long-term follow-up. This result suggest that prosthetic materials should be considered intraoperatively in particular in patients with large hiatal defects (>5cm) and when diaphragmatic tissues are inconsistent.

Surprisingly, the open approach in the present study was associated to better outcomes after RARS, unlike extensive data available [START_REF] Mertens | Morbidity and mortality in complex robot-assisted hiatal hernia surgery: 7-year experience in a high-volume center[END_REF][START_REF] Watson | Laparoscopic reoperation following failed antireflux surgery[END_REF][START_REF] Iqbal | Repair of 104 Failed Anti-Reflux Operations[END_REF][START_REF] Safranek | Results of laparoscopic reoperation for failed antireflux surgery: Does the indication for redo surgery affect the outcome?[END_REF][START_REF] Khajanchee | Laparoscopic Reintervention for Failed Antireflux SurgerySubjective and Objective Outcomes in 176 Consecutive Patients[END_REF][START_REF] Banki | Laparoscopic Reoperative Antireflux Surgery Is More Cost-Effective than Open Approach[END_REF][START_REF] Campo | Laparoscopic redo fundoplication improves disease-specific and global quality of life following failed laparoscopic or open fundoplication[END_REF][START_REF] Hashmi | A retrospective multicenter analysis on redo-laparoscopic anti-reflux surgery: conservative or conversion fundoplication?[END_REF][START_REF] Symons | Laparoscopic revision of failed antireflux surgery: a systematic review[END_REF] . We believe that this result was attributable to the re-operation rate. Indeed, more than half of the patients (6 over 11) in the open group were operated more than two times (mean of 3.8 operation) while in the mini-invasive group only 15.5% of them (16 over 103 patients) had repeated surgeries.

There are several limitations of this study. First, the retrospective design with missing informations and the heterogeneity of the data, including different indications for surgery, different surgical repair techniques and different meshes utilized.

Moreover, the exact technique provided in different surgical Units for the first surgery was not standardised. Repeat anti-reflux surgery is not standardized as well.

Authors also accept that classification of patients into those presenting recurrence of reflux disease and those with dysphagia with or without hiatal hernia recurrence is too simplistic for such a polymorphic and complex pathology. A more detailed classification considering frequency and severity of symptoms and anatomical features as well may be more accurate to explore the issue.

Study included also patients who underwent anti-reflux surgery more than two times. Furthermore, the preoperative assessment of QoL performed by an appropriate questionnaire for this disease (GERD Health-Related Quality of Life score) was not used.

Heterogeneity of the approach have to be reported as well. Open approach was preferred in multioperated patients and when strong adhesions were detected.

Control group including patients with GERD recurrence who was not re-operated is lacking.

Finally, despite a long study period, the follow up dropout rate was as high as 19%.

However, despite several limits, herein, we reported results (following STROCSS Guidelines 36 ) of a large cohort of patients who underwent repeat anti-reflux surgery from a multi-centre database. Surgical Units concerned are centres having a high degree of specialization in treating gastrooesophageal diseases. We share the same guidelines and similar surgical practice.

Conclusion

Repeat anti-reflux surgery is a safe and feasible procedure in high-volume centers, with acceptable perioperative outcome, comparable to those observed after PARS. Long-term outcomes can be considered as satisfying as after primary surgery, since it provides a success rate of almost 80%.

Advanced age and BMI <23 kg/m 2 were factor negatively impacting postoperative complications. The use of prosthetic materials for hiatoplasty was associated to better functional outcomes.

  , age > 70 years (33 patients out of 117, OR: 1.074, C.I.95% 1.018 -1.133, p=0.008) and body mass index (BMI) < 23 (ROC curve) (21 patients out of 117, OR 0.172, C.I.95% 0.052-0.568, p=0.004) were independently associated to the occurrence of postoperative complications.

Table 1 .

 1 Features of the cohort population studied. American society of anesthesiologists classification; BMI: body mass index; GERD : gastro esophageal reflux disease ; HH : hiatal hernia ; PARS : primary anri reflux surgery ; RARS : repeat anti reflux surgery.

	Features

F: female; M : male ; ASA:

Table 2 .

 2 Univariate analysis of the risk factors of postoperative complications after RARS.

	Features

ACKNOWLEDGEMENT

We would like to thanks the Dr. Marco G. Patti, MD, FACS. Professor of Medicine and Surgery. Co-Director, Center for Esophageal Diseases and Swallowing. Director of the Multidisciplinary Simulation Center, Department of Surgery. University of North Carolina School of Medicine for his critical review and suggestions.

AUTHOR DISCLOSURE

The authors (Fabrizio Panaro, Piera Leon, Thierry Perniceni, Giorgio Bianchi, Francois-Regis Souche, Jean Michel Fabre, Vito De Blasi, Santiago Azagra, Grégory Marin, Samir Jaber, Brice Gayet, Francis Navarro and David Fuks) have no conflicts of interest or financial ties to disclose.

Prosthetic material in

RARS