MD Maxime K Collard

Professor Jérémie H Lefevre
email: jeremie.lefevre@aphp.fr

MD Omar Ahmed

MD Thibault Voron

MD PhD Pierre Balladur

MD PhD François Paye

MD PhD Yann Parc

• O Ahmed

Ten-year impact of pancreaticoduodenectomy on bowel function and quality of life of patients with ileal pouch-anal anastomosis for familial adenomatous polyposis

Keywords: Prophylactic surgery, Wexner score, EORTC-QLQ-C30, Duodenal adenomatosis

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Familial adenomatous polyposis (FAP) is caused by an autosomal dominant mutation of the adenomatous polyposis coli (APC) gene. [START_REF] Groden | Identification and Characterization of the Familial Adenomatous Polyposis Coli Gene[END_REF] Colorectal polyposis is the earliest clinical manifestation of this mutation, which occurs during childhood or adolescence. [START_REF] Sarvepalli | Natural History of Colonic Polyposis in Young Patients with Familial Adenomatous Polyposis[END_REF] Because of the rapid progression of the polyposis and its very high risk of tumor transformation, a prophylactic coloprotectomy with ileal pouch-anal anastomosis (IPAA) is required; [START_REF] Vasen | Guidelines for the Clinical Management of Familial Adenomatous Polyposis (FAP)[END_REF] however, the best time to perform this radical surgery varies between patients. [START_REF] Sarvepalli | Web-Based Model for Predicting Time to Surgery in Young Patients with Familial Adenomatous Polyposis: An Internally Validated Study[END_REF] Initially when the number of rectal polyps is low, subtotal colectomy is sometimes preferred to coloproctectomy in order to achieve a better functional result, but the totalization by secondary proctectomy and IPAA is a mandatory second step in the majority of cases. [START_REF] Vasen | Decision Analysis in the Surgical Treatment of Patients with Familial Adenomatous Polyposis: A Dutch-Scandinavian Collaborative Study Including 659 Patients[END_REF] The efficient surgical management of colorectal polyposis has completely changed the prognosis of FAP. Today, duodenal or ampullary tumors and desmoid tumors are the two leading causes of death. [START_REF] Parc | Long-Term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy[END_REF] About 5% of patients will develop a duodenal or ampullary adenocarcinoma; [START_REF] Bülow | Duodenal Adenomatosis in Familial Adenomatous Polyposis[END_REF] therefore, a prophylactic surgical resection of the duodenum may be justified in patients with highly dysplasic duodenal polyps that are not endoscopically resectable.

The choice between pancreas-sparing duodenectomy and pancreaticoduodenectomy (PD) is debated, [START_REF] Vasen | Guidelines for the Clinical Management of Familial Adenomatous Polyposis (FAP)[END_REF] as the pancreas-sparing duodenectomy preserves the entire pancreatic parenchyma [START_REF] Augustin | Tailored Surgical Treatment of Duodenal Polyposis in Familial Adenomatous Polyposis Syndrome[END_REF] but is not adequate in patients with duodenal or ampullary adenocarcinoma, [START_REF] Parc | Surgical Management of the Duodenal Manifestations of Familial Adenomatous Polyposis[END_REF] and the diagnosis of these invasive tumors is frequently underestimated in FAP. [START_REF] Sourrouille | Surveillance of Duodenal Polyposis in Familial Adenomatous Polyposis: Should the Spigelman Score Be Modified?[END_REF][START_REF] Thiruvengadam | Spigelman Stage IV Duodenal Polyposis Does Not Precede Most Duodenal Cancer Cases in Patients with Familial Adenomatous Polyposis[END_REF] Thus, prophylactic surgery in FAP is unique as it may combine two major surgical procedures, both of which have significant consequences on quality of life (QoL). Moreover, operated patients are usually young and without invasive lesions. Thus, while their life expectancy is high, these patients will live for several decades with an IPAA and a PD. The life expectancy after prophylactic PD in FAP patients is therefore widely higher than in patients treated for pancreatic adenocarcinoma. [START_REF] Lubrano | Severe Postoperative Complications Decrease Overall and Disease Free Survival in Pancreatic Ductal Adenocarcinoma after Pancreaticoduodenectomy[END_REF] Ileal pouch-anal anastomosis is likely to alter patients' QoL, mainly due to impairment of bowel function and sometimes fecal continence. [START_REF] Parc | Long-Term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy[END_REF] PD also threatens patients' QoL and gastrointestinal function. [START_REF] Allen | Long-Term Quality of Life and Gastrointestinal Functional Outcomes After Pancreaticoduodenectomy[END_REF] This procedure can alter the bowel function in two ways: firstly, due to exocrine pancreatic insufficiency after resection of the pancreatic parenchyma; [START_REF] Sikkens | Prospective Assessment of the Influence of Pancreatic Cancer Resection on Exocrine Pancreatic Function[END_REF] and secondly, due to diarrhea induced by transection of the superior mesenteric nerve plexus during PD. [START_REF] Inoue | Optimal Extent of Superior Mesenteric Artery Dissection during Pancreaticoduodenectomy for Pancreatic Cancer: Balancing Surgical and Oncological Safety[END_REF] Therefore, the combination of a PD with an IPAA might potentiate the alteration of bowel function, as well as the negative impact on QoL. The impact of PD on the bowel function and fecal continence of these patients has not yet been explored.

Thus, our aim was to assess the long-term consequences of PD on bowel function, as well as the consequences on the QoL of FAP patients with an IPAA.

Methods

Patient selection

Among the patients with FAP who underwent coloproctectomy and IPAA at our center, we included all patients who underwent a PD between 1991 and 2017 (PD+IPAA group).

Patients who underwent total duodenopancreatectomy, pancreas-sparing duodenectomy, or who did not have a functioning IPAA at the time of the PD were excluded. Patients with an IPAA performed after the PD were also excluded. The conversion of an IPAA to an end ileostomy after the PD was not considered as an exclusion criterion.

Patients in the PD+IPAA group were matched with FAP patients who had undergone an IPAA after coloproctectomy, but without duodenal surgery (IPAA-only). This 1:1 matching was performed based on patient age at time of questionnaire, sex, ASA score and the presence of CRC at the time of IPAA. Regarding the coloproctectomy, we excluded patients with an end ileostomy, and those who had received pelvic radiotherapy. Since the intra-abdominal desmoid tumors can independently alter the QoL and also compromise the PD in case of invasion of the mesentery, these patients were excluded.

All of the PD and IPAA procedures were performed at our institution. The restorative procedure after PD was always standardized for the indication of duodenal or ampullary polyposis in FAP patients according to the modified Imanaga procedure. [START_REF] Imanaga | A New Method of Pancreaticoduodenectomy Designed to Preserve Liver and Pancreatic Function[END_REF] After pylorus preserving PD, the remnant pancreas was anastomosed to the posterior wall of the stomach by an end-to-side duct-to-mucosa anastomosis, then an end-to-end duodenojejunal anastomosis was made, followed by a hepaticojejunal end-to-side anastomosis 10 cm downstream [START_REF] Caillié | Severe Duodenal Involvement in Familial Adenomatous Polyposis Treated by Pylorus-Preserving Pancreaticoduodenectomy[END_REF] Thanks to this reconstruction, postoperative endoscopic explorations of the upper gastrointestinal tract to assess recurrence of polyposis in the jejunum is easier than after the Child's reconstruction. [START_REF] Child | Pancreaticojejunostomy and Other Problems Associated With the Surgical Management of Carcinoma Involving the Head of the Pancreas[END_REF] Moreover, this reconstruction conserves more length of functional small bowel for digestion which is probably useful in these patients without colon and rectum.

Medical records, operative and pathology reports were examined retrospectively.

Postoperative pancreatic fistulas (POPF) were classified according to the Revised 2016 ISGPS classification, thus, a biochemical leak was not considered as a POPF. [START_REF] Bassi | The 2016 Update of the International Study Group (ISGPS) Definition and Grading of Postoperative Pancreatic Fistula: 11 Years After[END_REF] This database was approved and registered (ref: 2211760v0) with the French National Data Protection Agency and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki (6th revision, 2008).

Questionnaires

Each patient (PD+IPAA and IPAA-only groups) was contacted by phone or mail or during a consultation in clinics and, after obtaining consent, a questionnaire containing the 30 questions from the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-30 v3 to assess the QoL [START_REF] Aaronson | The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in Oncology[END_REF] and five questions from the Wexner score to assess fecal continence was sent to patients. [START_REF] Jorge | Etiology and Management of Fecal Incontinence[END_REF] The EORTC-QLQ-30 v3 is a 30-item questionnaire evaluating one global health QoL scale (overall QoL), five functional scales (physical, role, cognitive, emotional and social) and nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) in patients with cancer. [START_REF] Aaronson | The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in Oncology[END_REF] High scores on global health QoL and functional scales indicate a high QoL, whereas high scores on symptom scales indicate severe symptoms. Although patients in this study did not have active cancer at the time of the interview, we selected this questionnaire because these patients were operated on for advanced dysplastic lesions or even for cancer, and the surgery performed was that used for cancer surgery. The Wexner score is a 5-item questionnaire which quantifies fecal incontinence with a score from 0 to 20 (a score of 0 is perfect continence, while 20 is total incontinence). [START_REF] Jorge | Etiology and Management of Fecal Incontinence[END_REF] In addition, patients were asked to quote their fecal frequency during the day, their nocturnal fecal frequency, their ability to defer defecation for 15 minutes and their daily constipation treatment. Patients in the PD+IPAA group were asked to specify their treatment regimen (anti-acid and pancreatic enzymes) and the presence of a delayed complication after PD (diabetes, cholangitis or pancreatitis). At last, PD+IPAA patients were asked two specific questions: "Did the resection of the duodenum and of part of the pancreas alter your quality of life?" and "Did the resection of the duodenum and of part of the pancreas alter your fecal continence?".

Statistical analysis

Quantitative data were expressed as the median and interquartile range (IQR), and values were compared using the Mann-Whitney U test. Qualitative data were reported as frequencies and percentages and compared using the χ² test or the Fisher exact test, as appropriate. All of the tests were two sided. A p-value of <0.05 was considered to be statistically significant.

Scoring of the EORTC QLQ-C30 questionnaire was performed according to the EORTC QLQ-C30 Scoring Manual, [START_REF] Fayers | behalf of the EORTC Quality of Life Group[END_REF] with linear transformation of the raw scores to provide ranges from 0 to 100. All analyses were performed using SPSS software (version 23; IBM Corp, Armonk, NY, USA).

Results

Population, surgical procedures and outcomes

From the 58 surgically treated patients in our center between 1991 and 2017 for duodenal or ampullary polyposis associated with FAP, we identified 32 patients with a PD who met the inclusion criteria (Figure 1). These 32 PD+IPAA patients were matched to 32 IPAA-only patients among 127 patients. In the PD+IPAA group, the response rate to the questionnaire was 78% (25/32). Among the IPAA-only patients, the response rate was identical (25/32, 78%). All patients responded to the whole questionnaire and there was therefore no missing data.

At the time of the interview, the median age was 56.7 years (49.5-67.3) for PD+IPAA patients and 56.6 years (41.2-68.5) for IPAA-only patients. No significant post-matching differences were found between PD+IPAA and IPAA-only responder patients for all the matching criteria. Moreover, the baseline characteristics and IPAA data were comparable between the two groups, as shown in Table 1. Among the 7 patients with an invasive colorectal tumor identified after coloproctectomy, none had tumor recurrence at the time of completing the questionnaire after a median follow-up of 13.0 years (10.7-23.0).

For PD+IPAA patients, the median age at the time of the PD was 47.7 years (40.5-57.0) and the delay between the IPAA and the PD was 14.3 years (11.3-22.4) and the delay between the PD and the interview was 9.8 years (4.4-13.0). The median duration of the surgery was 380 minutes (367-400). Details concerning postoperative complications after the PD are presented in 2.

Bowel function and fecal continence

A comparison of bowel function and fecal continence of IPAA+PD and IPAA-only patients is reported in Table 3. None of the analyzed criteria significantly differed between the two groups. Notably, there were no differences in daytime fecal frequency (p = 0.362), nighttime fecal frequency (p = 0.830), incontinence for gas (p = 1.000) or incontinence for stool (p = 0.564). The Wexner score was similar between the two groups (p = 0.984).

At the time of the interview, compared to before the PD, 68% (17/25) of PD+IPAA patients reported no change in daytime fecal frequency and the number of stools per night was unchanged before and after PD for 72% (18/25) of patients (Table 3). A majority of the patients (64%) declared that the PD did not alter the fecal continence at all (Figure 2 and in BMI (p=1.000). Similarly, daily antacid intake did not affect daytime fecal frequency (p=0.383), nighttime fecal frequency (p=0.522), taking constipating medicine (p=0.677) and BMI (p=0.637).

Quality of life

The global health QoL, evaluated by the EORTC-QLQ-30 v3, was similar between IPAA+PD and IPAA-only patients, with scores of 83.3/100 (62.5-87.

Discussion

Performing PD in FAP patients with an IPAA preserves both the bowel function, including fecal continence, and the QoL. Knowledge of the long-term consequences of PD is mandatory in the context of preventive surgery in young patients of working age. Thanks to these data about patients living with both PD and IPAA, the surgeon and physician will be able to provide better information to FAP patients. To our knowledge, this is the first study to compare the bowel function and QoL between PD+IPAA patients and IPAA-only patients in the context of FAP.

In regard to the functional consequences, this study reported similar bowel function and a similar rate of fecal incontinence between the PD+IPAA and IPAA-only groups. Furthermore, the Wexner score did not differ between the two groups. Although PD is not directly responsible for fecal incontinence, it was essential to specifically assess the risk of fecal incontinence in this work. Indeed, PD is a surgical procedure that may cause diarrhea via exocrine pancreatic insufficiency [START_REF] Sikkens | Prospective Assessment of the Influence of Pancreatic Cancer Resection on Exocrine Pancreatic Function[END_REF] and superior mesenteric nerve plexus injury. [START_REF] Inoue | Optimal Extent of Superior Mesenteric Artery Dissection during Pancreaticoduodenectomy for Pancreatic Cancer: Balancing Surgical and Oncological Safety[END_REF] In patients who already have an IPAA, the change in stool texture and increased number of stools per day are correlated with the appearance or aggravation of fecal incontinence. [START_REF] Tomita | Defecation States in Patients with or without Soiling at 5 Years or More after Colectomy, Mucosal Proctectomy and Ileal J Pouch-Anal Anastomosis for Ulcerative Colitis[END_REF] This fecal incontinence represents one of the most disabling functional consequences, and has a major impact on the QoL. [START_REF] Mckenna | Fecal Incontinence Reduces Quality of Life More Than You May Think[END_REF] Therefore, analysis of this criterion in the context of the combination of PD and IPAA was required. Two factors may alter bowel function and fecal continence after PD. Firstly, a lesion of the superior mesenteric nerve plexus which risk is proportional to the extent of lymph node dissection on the right side of the superior mesenteric artery (station 14). [START_REF] Inoue | Optimal Extent of Superior Mesenteric Artery Dissection during Pancreaticoduodenectomy for Pancreatic Cancer: Balancing Surgical and Oncological Safety[END_REF] As PD is mostly performed for non-invasive lesions, lymph node dissection of station 14 on the superior mesenteric artery was not extensive, thereby reducing the risk of superior mesenteric nerve plexus injury that can potentially cause diarrhea. In addition, the extended delay after PD observed in this study (median of 9.8 years) could have influenced this result.

Nimura et al. observed the disappearance of the diarrhea caused by nerve lesions one year

after PD in the setting of an extensive lymphadenectomy. [START_REF] Nimura | Standard versus Extended Lymphadenectomy in Radical Pancreatoduodenectomy for Ductal Adenocarcinoma of the Head of the Pancreas: Long-Term Results of a Japanese Multicenter Randomized Controlled Trial[END_REF] Then, the functional results within the first post-operative years is probably less favorable than the bowel function presented in our results. Furthermore, para-aortic lymph node sampling was never performed in contrast to PD for pancreatic adenocarcinoma. [START_REF] Schwarz | Para-Aortic Lymph Node Sampling in Pancreatic Head Adenocarcinoma[END_REF] Secondly, exocrine pancreatic insufficiency which risk is also lower for this indication of PD performed on a healthy pancreatic parenchyma without obstructive pancreatitis observed in PD for pancreatic cancer. [START_REF] Nakamura | Predictive Factors for Exocrine Pancreatic Insufficiency after Pancreatoduodenectomy with Pancreaticogastrostomy[END_REF] In addition, 84% of patients took pancreatic enzyme supplementation daily, thereby diminishing diarrhea associated with a potential exocrine pancreatic insufficiency. The relation between PD and bowel function is complex and many other mechanisms can be invoked such as dumping syndrome or bile alterations. Recently, the consequences of PD on the intestinal microbiota have been documented, which provides a major research perspective in understanding the impact of PD on the bowel function. [START_REF] Rogers | Disturbances of the Perioperative Microbiome Across Multiple Body Sites in Patients Undergoing Pancreaticoduodenectomy[END_REF] Preservation of long-term QoL in the PD+IPAA group compared to the IPAA-only group can be largely explained by the absence of deterioration of bowel function and fecal continence after PD. In addition, the indication for PD, which is predominantly preventive in patients without invasive lesions, is another possible explanation for the preservation of QoL. Indeed, it has been shown that fear of tumor recurrence significantly deteriorates patients' QoL after PD. [START_REF] Petzel | Fear of Cancer Recurrence after Curative Pancreatectomy: A Cross-Sectional Study in Survivors of Pancreatic and Periampullary Tumors[END_REF] However, several studies have demonstrated that QoL after PD for benign lesions is comparable to the QoL after PD for malignant lesions. [START_REF] Allen | Long-Term Quality of Life and Gastrointestinal Functional Outcomes After Pancreaticoduodenectomy[END_REF][START_REF] Fong | Health-Related Quality of Life and Functional Outcomes in 5-Year Survivors After Pancreaticoduodenectomy[END_REF] In the literature, the rate of new-onset diabetes after PD varies between 12% and 22%. [START_REF] Orfanidis | Extended Follow-Up and Outcomes of Patients Undergoing Pancreaticoduodenectomy for Nonmalignant Disease[END_REF][START_REF] Maxwell | Development of Diabetes after Pancreaticoduodenectomy: Results of a 10-Year Series Using Prospective Endocrine Evaluation[END_REF][START_REF] Kusakabe | Long-Term Endocrine and Exocrine Insufficiency After Pancreatectomy[END_REF][START_REF] Beger | New Onset of Diabetes and Pancreatic Exocrine Insufficiency After Pancreaticoduodenectomy for Benign and Malignant Tumors: A Systematic Review and Meta-Analysis of Long-Term Results[END_REF] In our study, 26% developed this delayed complication. This percentage is quite high as the PD was predominantly carried out in young adults with a low BMI, favoured by the associated IPAA. In addition, PD on patients with soft pancreas is theoretically a protective factor for post-PD new-onset diabetes. [START_REF] Hirata | Predictive Factors for Change of Diabetes Mellitus Status after Pancreatectomy in Preoperative Diabetic and Nondiabetic Patients[END_REF] Orfanidis et al. reported a post-PD new-onset diabetes rate for nonmalignant disease of 12.5% after a median follow-up of 2.8 years. [START_REF] Orfanidis | Extended Follow-Up and Outcomes of Patients Undergoing Pancreaticoduodenectomy for Nonmalignant Disease[END_REF] Therefore, the high rate of new-onset diabetes in our study can probably be explained by the long median followup period of 9.8 years after PD, considering that the median time to onset of neo-diabetes was 10.0 years. This long-term risk is very important for the indication for PD in FAP patients because this preventive surgery is associated with a long-life expectancy. On one hand, this finding means that patients can be informed of the real risk of developing diabetes in the longterm. On the other hand, this result highlights the importance of regularly screening IPAA+PD patients for the development of new-onset diabetes in the years following pancreatic surgery. [START_REF] Mannucci | Is Glucose Control Important for Prevention of Cardiovascular Disease in Diabetes?[END_REF] One limit of this study is that the predictive factors of new-onset diabetes were not identified because of the small number of patients in our series with this delayed complication (six patients). However, the BMI was very similar between non-diabetic The onset of delayed diabetes after PD was associated with a significant decrease in QoL, even if bowel function and fecal continence were preserved. This association between diabetes and impaired QoL has been described in the literature. [START_REF] Goldney | Diabetes, Depression, and Quality of Life: A Population Study[END_REF] These data argue for pancreas-sparing duodenectomy as this surgical procedure preserves the entire pancreatic parenchyma, with a postoperative morbidity comparable to PD. [START_REF] De Castro | Pancreas-Preserving Total Duodenectomy versus Standard Duodenum[END_REF] Nevertheless, this surgical alternative should not be proposed in case of doubt about the presence of a duodenal tumoral lesion. [START_REF] Parc | Surgical Management of the Duodenal Manifestations of Familial Adenomatous Polyposis[END_REF] The preoperative diagnosis of invasive duodenal lesion in duodenal polyposis is really difficult, as demonstrated in our series, where the presence of an invasive duodenal lesion preoperatively missed in 75% of cases. Interestingly, Ganschow et al. showed that QoL after pancreas-sparing duodenectomy was similar to that of PD in patients with FAP. [START_REF] Ganschow | Postoperative Outcome and Quality of Life after Surgery for FAP-Associated Duodenal Adenomatosis[END_REF] However, the limited number of patients who had a PD (11 patients) and with a mean follow-up (4.9 years) shorter than ours probably led to an underestimation of the risk of new-onset diabetes, which was only of 9% in this study from Ganschow et al. [START_REF] Ganschow | Postoperative Outcome and Quality of Life after Surgery for FAP-Associated Duodenal Adenomatosis[END_REF] Performing PD in FAP patients with an IPAA does not alter both the bowel function, including fecal continence, and the QoL. Nevertheless, about one quarter of patients will develop new-onset diabetes after a median delay of 10 years after PD. This delayed complication negatively impacts patients' QoL. Thus, regular screening for new-onset diabetes after PD is required in order to treat it as efficiently as possible and to preserve the patient's QoL. * Data are presented as number of cases (percentage of cases). † Post-operative pancreatic fistula defined according to the Revised 2016 ISGPS classification. [START_REF] Bassi | The 2016 Update of the International Study Group (ISGPS) Definition and Grading of Postoperative Pancreatic Fistula: 11 Years After[END_REF] Biochemical leak (formerly Grade A) is not considered to be a postoperative pancreatic fistula in this revised classification.

FIGURES TITLES AND LEGENDS

  -A). All patient had a functioning IPAA at the time of the interview and conversion to an end ileostomy after PD was never required either because of bad bowel function or for other reasons. Patients treated by pancreatic enzymes had no change in daytime fecal frequency (p=0.858), in nighttime fecal frequency (p=0.369), in taking constipating medicine (p=0.105)

5 ) 4 .

 54 and 83.3/100 (62.5-100), respectively (p=0.401). None of the functioning and symptom scales analyzed by the EORTC-QLQ-30 v3 questionnaire differed significantly between the two groups, as shown in Table 84% (21/25) of PD+IPAA patients declared that the PD did not alter or alter only a little their quality of life (Figure 2-B) Among the IPAA+PD patients, the global health QoL was significantly impaired in patients with new-onset diabetes compared to those without (54.2/100 [33.3-77.8] and 83.3/100 [75.0-91.7], respectively; p = 0.011). This reduction in QoL was not associated with an alteration in fecal continence, as assessed by the Wexner score (2.0/20 [2.0-6.3] and 4.0/20 [0-8.0], respectively; p = 0.475), nor with a modification in bowel function (7.5 stools per day [6.3-11.8] and 6.0 stools per day [4.0-8.0], respectively; p = 0.092).

Figure 1 :

 1 Figure 1: Flow chart of the patients who underwent radical surgery for duodenal polyposis

Figure 2 :

 2 Figure 2: Responses to the specific questions asked to PD+IPAA patients (n=25) about the

Table 2 .

 2 Pathological examinations of the operative specimens are exposed in

Table 1 .

 1 In patients with a duodenal invasive adenocarcinoma, the median number of lymph nodes analyzed in the operative specimen was 14.5(12-17). 75% of patients with an invasive adenocarcinoma (3/4) were not diagnosed preoperatively as invasive cancer but as duodenal dysplasia. The two patients with a lymph node involvement received 12 cycles of FOLFOX as adjuvant chemotherapy. At the time of the questionnaire, none of these patients had tumor recurrence after a median follow-up of 11.0 years (4.3-13.2).

	Delayed complications after PD
	Of the PD+IPAA patients, 84% (21/25) reported taking pancreatic enzymes and 64% (16/25)

anti-acid medications. Diabetes was the most frequent delayed complication in these patients. Of the 23 patients who were not diabetic before the PD, 26% (6/23) developed new-onset diabetes after a median period of 10.0 years (4.3-13.6) after the pancreatic surgery. No patient developed a new-onset diabetes immediately after the PD. The body mass index (BMI) was similar between non-diabetic patients and new-onset diabetic patients (23.8 kg/m 2 [22.1-25.8] and 24.9 kg/m 2 [22.6-27.3], respectively; p = 0.354). Regarding the two patients with preexisting diabetes, both increased their treatment after the PD from an oral hypoglycemic agent to insulin. Three patients (12%) developed late acute pancreatitis after PD: 2 because of stenosis of the pancreaticogastrostomy and one with no identified cause. Other delayed complications are presented in Table

Table 2 .

 2 Early and delayed postoperative complications of pancreaticoduodenectomy.

	PD+IPAA
	n = 25

* Data are presented as number of cases (percentage of cases). † Data are presented as median (interquartile range).


Pierre-Marie Aubert
email: pierremarie.aubert@iddri.org

Rémy Ruat

Sébastien Treyer

Aleksandar Rankovic

policy-makers and civil society in the development of a voluntary initiative, the "4 per 1000: Soils for food security and climate"

Keywords: Soils, climate, multistakeholder partnerships, science and policy, 4 per 1000

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Soils have increasingly gained visibility in the international agenda over the last decade [START_REF] Montanarella | Govern our soils[END_REF]. This is clearly illustrated by the number of initiatives launched from 2012 to 2015, from the creation of the Global Soil Partnership in 2012 to the launch of the initiative "4 per 1000: Soils for Food Security and Climate " ("Initiative 4 pour 1000" in French, 4PM hereafter) in March 2015. Despite this increased visibility, it is however still not clear how this will, in practice, lead to the social transformations that are required to conserve soils. Indeed, most of those initiatives can be considered "multi-stakeholder partnerships" and are voluntary in nature. This is particularly the case of the 4PM initiative, whose aim is to increase soil organic carbon (SOC) stocks worldwide, in order to simultaneously address climate change mitigation, adaptation and food security issues, and which is part of the Global Climate Action Agenda.

While such voluntary, multistakeholder partnerships (involving local and national governments, the private sector, NGOs, research institutions, etc.) have been presented as major cornerstones of the implementation of both the Paris Agreement and the Sustainable Development Goals (SDGs), they have so far demonstrated little effectiveness. Four main criticisms have been expressed vis-à-vis such partnerships: (i) a large part of them have been inactive since their creation some years ago; (ii) they do not target the areas/sectors that are in the most need of external intervention (e.g. [START_REF] Biermann | The overall effects of partnerships for sustainable development: more smoke than fire?[END_REF]; (iii) the type of solutions they promote are often mostly conservative and they do not insist enough on the need for systemic changes, not least because they tend to be dominated by private interests [START_REF] Beisheim | Multi-Stakeholder Partnerships for Implementing the 2030 Agenda: Improving Accountability and Transparency[END_REF]; and (iv) they lack accountability, both internally and externally [START_REF] Bäckstrand | Multi-stakeholder partnerships for sustainable development: rethinking legitimacy, accountability and effectiveness[END_REF][START_REF] Bäckstrand | Transnational public-private partnerships[END_REF].

Against this backdrop, some authors have tried to identify "key conditions for success", which include, amongst others, the need to include all relevant actors on board, to clearly define the theory of change of the initiative, to devote human, financial and material means for the functioning of the initiative, and to develop a robust and open monitoring, reporting, and evaluation system (e.g. Pattberg & Widerberg, 2016, p. 48). Despite their importance, we contend these recommendations do not to consider two aspects central to the success of any voluntary initiatives. One concerns the way in which the initiative deals with the tension inherent to any voluntary approach between its level of ambition and its capacity to widely enrol stakeholders. Both aspects are indeed needed for the initiative to address the drivers of the problems it wishes to tackle, and thus be transformative [START_REF] Loorbach | Sustainability Transitions Research: Transforming Science and Practice for Societal Change[END_REF]: to be ambitious on its goals and to gather a broad range of actors. However, they do not easily go hand in hand: being too ambitious generally leads to little enrolment; while a lower level of ambition allows to broaden the range of actors enrolled, it also reduces the transformational potential of the initiative.

Another key missing element in the literature concerns the knowledge dynamics at play and the role of scientists inside these initiatives. Setting ambition, learning from experimentation and having accountability all contain a central question of what and whose knowledge will be mobilised: to define the level of ambition and what is to be achieved/transformed; to monitor what's being done and with what effect and to indeed learn from it; to hold the different constituencies of the initiative accountable on whether and how the initiative delivered or not.

The 4PM initiative is an interesting case study to discuss both of these aspects by addressing the following questions:

(i) How could scientists contribute to the emergence and the structuration of a voluntary initiative, and more particularly to the definition of its ambition? (ii) How could they contribute to the enrolment of the other stakeholders participating to the initiative?

(iii) Finally, to what extent could their contribution influence the transformational capacity of an initiative?

As stated above, the 4PM initiative intends to favour an increase in soil organic carbon stocks to simultaneously contribute to food security and climate change adaptation and mitigation through large scale and systemic changes in agricultural practices. It has three main features which will allow us to derive insights applicable to other multi-stakeholder partnerships: (i) it is simultaneously a research programme and an action programme, which means that scientists have been granted a key role in it; (ii) it has been endowed with ambitious objectives; (iii) at the end of 2018, it gathered 359 partners1 which shows, at least, the interest it has generated amongst different stakeholders.

Besides that, this paper also intends to contribute to on-going discussions amongst soil scientists about the relevance and the potential impact of the 4PM initiative [START_REF] Chambers | Soil carbon sequestration potential of US croplands and grasslands: Implementing the 4 per Thousand Initiative[END_REF][START_REF] Lal | Beyond COP 21: Potential and challenges of the "4 per Thousand" initiative[END_REF][START_REF] Baveye | The "4 per 1000" initiative: A credibility issue for the soil science community?[END_REF]Minasny et al., 2017a ;Minasny et al., 2017b ;VandenBygaart, 2017 ;White et al., 2017). From the point of view of soil sciences, the main debates indeed revolve around the uncertainties about the 4PM objectives and how to technically achieve and monitor them. Yet, this literature tends to oversimplify the broader political dimension of 4PM, at least on two levels. Firstly, the launch of the initiative by French minister Le Foll is often taken as a starting point of 4 PM discussions, while its origins and its broader objectives are seldom discussed. Rather, how the 4PM story is usually told is strongly tainted by the "linear model" vision [START_REF] Beck | Moving beyond the linear model of expertise? IPCC and the test of adaptation[END_REF] of the actually complex interactions between science and policy, as if the 4PM was simply the result of Le Foll and his staff finally understanding (and with the risk of misunderstanding) the recommendations of soil sciences, who now try to opportunistically apply them as an easy fix to climate change (e.g. [START_REF] Baveye | The "4 per 1000" initiative: A credibility issue for the soil science community?[END_REF]. This narrative completely obliterates the question of what the 4PM promoters, and Le Foll's administration in particular, actually saw in the 4PM in the wider context of international struggles around the transition of agricultural systems towards sustainability. Secondly, this narrative too narrowly focuses on scientists and policy-makers, and leaves aside all the other voices that have been raised, especially from civil society, during the development of 4PM and its current functioning. To our minds, these two aspects are however central in order to fully appreciate what 4PM is trying to do and provide a more useful critique, geared towards enhancing its transformative potential towards sustainability [START_REF] Ruat | Which accountability framework and which transformational potential of a multi-stakeholder initiative? the case of the 4‰ Initiative[END_REF][START_REF] Treyer | Implementing the "4 per 1000" initiative: contribution for the establishment of a reference/ normative framework[END_REF].

Conceptually, the paper builds upon the literature addressing voluntary initiatives to discuss the 4PM case to make recommendations against this backdrop [START_REF] Bäckstrand | Transnational public-private partnerships[END_REF]Beisheim & Liese, 2014 ;[START_REF] Van Asselt | Reinvigorating International Climate Policy: A Comprehensive Framework for Effective Nonstate Action[END_REF][START_REF] Pattberg | Transnational multistakeholder partnerships for sustainable development: Conditions for success[END_REF]. The paper also draws from science and technology studies to (i) describe and analyse the processes of translation [START_REF] Callon | Some Elements of a Sociology of Translation: Domestication of the Scallops and the Fishermen of St Brieuc Bay[END_REF][START_REF] Latour | Pandora's hope: essays on the reality of science studies[END_REF] in which promoters of 4PM have engaged in order to achieve their objectives, and (ii) to describe how relationships between scientists and other actors have evolved so far in the 4PM, and to discuss aspects of inclusiveness and accountability (Jasanoff, 2003a(Jasanoff, , 2003b[START_REF] Jasanoff | Technologies of humility[END_REF], especially in regards to how 4PM was framed and what this entails for its transformative potential.

The paper relies on an intervention-research project carried out from mid-2015 up to the beginning of 2017, and continuous observation of the 4PM developments since then. The project's goals were to follow and analyse the emergence of 4PM, as well as to interact with the actors involved in 4PM (in the French context especially) to foster dialogue and make proposals for the initiative's framing [START_REF] Ruat | Which accountability framework and which transformational potential of a multi-stakeholder initiative? the case of the 4‰ Initiative[END_REF][START_REF] Treyer | Implementing the "4 per 1000" initiative: contribution for the establishment of a reference/ normative framework[END_REF]. To document the early stages of the 4PM initiative, the paper primarily relies on three main sources of data, gathered since September 2015:

• Participant observations during several events and workshops organised in the context of the 4PM initiative, ranging from official events during UNFCCC COP 21 and COP 22, scientific workshops, and workshops we organized ourselves with NGOs and scientists at different points of the whole process;

• A series of 19 semi-structured interviews carried out with key stakeholders from civil society organisations (4), research institutions (9), international organisations (2), and administrative bodies (5);

• The analysis of all reports and grey literature published on 4PM.

The paper reports on two main results. From an empirical point of view, it will show that the strong involvement of soil scientists in the design of the 4PM initiative, as well as in the enrolment of other stakeholders, has had dual consequences: on the one hand, it has reinforced the initiative's scientific credibility (Cash et al., 2003) by keeping most discussions at a mere technical level, considering soil organic carbon sequestration as the main (if not the sole) proxy for mitigation, adaptation, and food security. On the other hand, this technical approach has led the initiative to face difficulties to enrol representatives from peasant and familial agricultures, who have criticized the absence of clear definitions of the type of agricultural models the 4PM intends to promote. From a more analytical point of view, this case study will lead us to support Jasanoff's claim that scientists intervening in policy arenas should be "held to norms of transparency and deliberative adequacy that are central to democratic governance" (Jasanoff, 2003a, p. 157).

The remainder of this paper is organised as follows. Section 2 will further present the 4PM initiative background and objectives. Section 3 and 4 will develop our main empirical results, while section 5 concludes the paper by discussing the main political and theoretical implications of our results. The role that soils could play to combat climate change has long been identified and discussed among soil scientists and beyond. A seminal paper by Paustian and colleagues (1997) identified the potential for soil carbon sequestration to be up to 20-30 Gt of C over the next 50-100 years, while pointing to the many co-benefits associated with soil carbon sequestration, and in particular the improvement of soil quality and, in turn, of agricultural productivity and sustainability. This argument was further refined by subsequent research, which were synthesised in a couple of key papers [START_REF] Smith | Meeting Europe's climate change commitments: quantitative estimates of the potential for carbon mitigation by agriculture[END_REF][START_REF] Lal | Soil Carbon Sequestration Impacts on Global Climate Change and Food Security[END_REF]Lal, 2004a ;[START_REF] Smith | Carbon sequestration in croplands: the potential in Europe and the global context[END_REF].

The

The topic also gained prominence in the French debate around soils, agriculture, and climate change. In 2001, a report mandated by the Ministry of the Environment identified the potential for soil carbon sequestration to be up to 2 % of French total emissions of greenhouse gases. It however pointed out the many uncertainties associated to such an approach to climate mitigation: soil carbon sequestration processes are context dependent, reversible, and in large part unknown; and the evolution of soil organic carbon stocks is difficult to measure and, hence, to account for in the French greenhouse gas inventory (Arrouays et al., 2002, p. 315). A decade later however, a new collective expertise nuanced this judgement given the progresses made in the scientific understanding of soil carbon sequestration processes [START_REF] Pellerin | Quelle contribution de l'agriculture française a ̀ la re ́duction des e ́missions de gaz a ̀ effet de serre ? Potentiel d'atte ́nuation et coût de dix actions techniques[END_REF].

It is on the basis of these reports that, during the Climate Smart Agriculture Conference held in Montpellier, in March 2015, French minister Le Foll first spoke about an ambitious research programme on the role of soils in climate change mitigation, which would be led by France. Le Foll's proposal was underpinned by his understanding of the soil carbon sequestration equation: the idea that an increase of soil organic carbon stocks of 4 per 1000 per year could be enough to offset anthropogenic emissions coming from fossil fuel and cement. Whatever the controversies this figure yielded -to which we will return in the following paragraph -the idea was taken up by Laurence Tubiana, the then French Ambassador for Climate Change in charge of the UNFCCC COP 21 negotiations. A month later, on April 27 th 2015, Tubiana and Le Foll jointly held a press conference to announce that the 4PM initiative would be part of the Action Agenda of the COP 21.

With this announcement, Le Foll and Tubiana (who had also been Prime Minister councillor for agricultural affairs between 1997 and 2002) first wanted to foster the integration of agriculture into climate change negotiations, which had by then been a matter of tough international discussion for more than 15 years. But they were, also, trying to reframe the international debate on agriculture, which was in a state of deadlock since, at least, clashes surrounding the International Assessment on Agricultural Science, Technology and Development (IAASTD) in 2009. While the launch of the Climate Smart Agriculture movement, a few years later, was endowed with a similar ambition -"to promote a paradigm shift in agriculture at all levels" (CSA Scientific Conference, 2010) -Climate smart Agriculture had ended up in 2015 as a highly contested "Global Alliance for Climate Smart Agriculture" with no clear normative directions.2 Against this backdrop, Le Foll's ambition was to promote a more radical change and to think about agricultural models' transition, as he had been doing in France since he was appointed.

From this perspective, the climate agenda was 'used' by Le Foll to promote a much broader agenda focused on agricultural transition issues. As he put it two years later during COP 22:

"With the 4PM, we are trying to think about models of agricultural production, we are trying to think about the mutation of agricultural systems which is ineluctable. The model of green revolution arrives at the end of a cycle. We are trying to open a new cycle, an agriculture less intensive in machines, much less in chemicals, turned towards the use of natural mechanisms, the functioning of ecosystems, which are all different. It is on this basis that we seek to build a commitment in the frame of our fight against climate change, but also to think about the mutation which is occurring for agricultural models." (French Minister Le Foll, during the 4PM side event at the COP22)

The ultimate objectives of the 4PM were initially presented as follows: (i) developing knowledge, projects and policies to enable significant and continued increases in soil organic carbon stocks in order to (ii) jointly contribute to food security, climate change mitigation and climate change adaptation. 3For some scientists who had been advocating for a better consideration for soils in the political agenda for decades, the launch of this initiative was seen as a great victory. Some tensions however appeared in the scientific community about whether policy-makers brought soils in their agenda "in the right way". For some of them, the way in which Le Foll presented the 4 PM was indeed too simplistic and did not reflect the complexity of the problem (see also [START_REF] Kon | Soil sciences and the French 4 per 1000 Initiative-The promises of underground carbon[END_REF]. They criticized both the figure used and the principle behind -that is, the fact that soil carbon sequestration could compensate most (if not all) anthropogenic emissions -which was considered as a potentially good excuse for large emitters to stop or slow down their mitigation efforts (personal communications; see also [START_REF] Baveye | The "4 per 1000" initiative: A credibility issue for the soil science community?[END_REF][START_REF] Kon | Soil sciences and the French 4 per 1000 Initiative-The promises of underground carbon[END_REF].. On the other hand, other scientists stressed the unique opportunity it presented to soil scientists to get their message across in the policy arena: "It is not that important to engage in a battle of scientific numbers, but really to recognize that there is a 'slogan' carried by a minister, and internationally, which can put back soils at the core of national and international debates! Indeed, there will be a need to decode and explain… But battle over numbers among experts are generally perceived by politicians as the good reason for not doing anything! The most important message is that the management (good or bad) of soils can in fine influence the global CO2 balance" (a French scientist answering to a colleague criticizing the figure and the principle behind the 4PM, during a workshop).

Over the following six months, Le Foll's administration worked closely with French soil scientists from different research institutes to develop the initiative. The next two sections describe the type of cooperation that took place between them during this period and how this has eventually determined both the content of the initiative and its capacity to enrol stakeholders.

Carbon chains: binding objectives and actors together with the help of soil organic matter

Six months ahead of the COP 21, when the 4PM was officially launched as part of the Global Climate Action Agenda, the French Minister and his scientific allies (hereafter refered to as "the 4PM promoters) had to recruit other partners. Initiatives of the Global Climate Action Agenda are indeed voluntary in nature. Their potential impact depends to a large extent upon the number and the quality of members they manage to attract. 4PM promoters targeted four main types of actors to ensure the success of the initiative: states, civil society organisations, international organisations (in particular the Food and Agriculture Organization of the United Nations -FAO -for its key role at the interface between agriculture and climate change issues), and soil scientists or other scientific colleagues. Although promoters also deemed farmers and their representative organisations to be key actors to get on board, our observations suggest that they were not as central as the four types above in their strategy.

13 Based on the concept of problematization forged by [START_REF] Callon | Some Elements of a Sociology of Translation: Domestication of the Scallops and the Fishermen of St Brieuc Bay[END_REF], Figure 1 illustrates the way in which 4PM promoters conceived of the objectives of the four types of actors we mentioned, and how they thought the increase of soil organic carbon stocks could actually constitute an obligatory passage point for all of them. The focus was clearly put on the multiple benefits associated with an increase in soil carbon stocks which was seen at the crossroads of the objectives of all actors.

4PM promoters

For southern/developing countries, in debates around climate change, the main issue when talking about agriculture and climate change has always been that of adaptation. From that perspective, an increase in soil organic carbon was presented by the 4PM promoters as a way to increase soil fertility and hence, to favour adaptation and food security.

For developed countries, where industrial agriculture is well developed, the question of how to mitigate greenhouse gas emission in the agricultural sector while avoiding too stringent regulation is key. Here, available practices and techniques with the potential to favour soil carbon sequestration makes the 4PM objectives interesting to answer their needs.

For international organisations, and in particular the FAO, a key concern has long been to ensure a coherent implementation of the three so-called "Rio Conventions" (on desertification, climate change and biodiversity). In this perspective, the multiple dimensions of soil organic carbon sequestration are depicted as an excellent vehicle to achieve such a goal [START_REF] Montanarella | Putting soils on the agenda: The three Rio Conventions and the post-2015 development agenda[END_REF].

4PM promoters saw civil society organisations, especially those involved in rural development and food security issues in developing countries, to have two main questions on their agenda. First, how can one limit or even avoid that climate change mitigation actions negatively impact food security or the right to food for rural populations of least developed countries? Second, how can agroecology and agroecological practices against agro-industrial development in those same areas be promoted? Against this backdrop, targeting an increase in soil organic carbon is presented as a way to simultaneously promote agroecological practices, favour soil fertility, and hence food security and adaptation to climate change.

Last but not least, soil scientists were considered as key participants to target for the 4PM promoters, as their participation is necessary to ensure the full success of the scientific part of the initiative. Their interest was supposed to lie mainly in the possibility to carry out further research, which means to get additional research funding, but also to reach out to the entire world to advocate for the importance of soils in sustaining human life on Earth. On both topics, the 4PM promoters expected to be able to give them interesting perspectives.

With this problematization, the 4PM promoters used the multifunctionality of soil organic carbon to bind together all the objectives, and thus the actors that were pursuing them, in this multistakeholder voluntary initiative. However, by doing so, they also bound themselves, as we shall see, to a relatively narrow -albeit terribly complex -approach to define and monitor the objectives and achievements of 4PM -that is to define suitable metrics and methodologies to follow the evolution of soil organic carbon stocks over time. It seems that this was a deliberate choice, in line with what we discussed in the previous section: overemphasizing the "climate" dimension of 4PM, and its technicalities around soil carbon dynamics, were part of a strategy aimed at avoiding upfront and conflicting discussions on agricultural models per se.

We believe this constituted the principal answer of 4PM to the challenge voluntary initiatives face, as described in the introduction: having an extremely high ambition for the transformation of agriculture that is carried inside the climate arena, and mediating it through soil carbon in order to gather a vast number of actors. There lies, in our view, the central bet of 4PM, and a source of much tension: soil carbon is not that easy to tame, and the expectations of other actors are not that easy to bend.

Gaining in size and power: how scientists and policy-makers cooperate to control soils and attract stakeholders

After this first moment of definition, the 4PM promoters deployed a series of devices and strategies to interest key actors from May 2015 to the end of 2016. In June 2017, two years after its launch, the 4PM initiative had already been joined by almost 220 members, out of which were 36 countries, 11 international organisations, 39 research organisations and 61 NGOs. At first glance, this could indicate that the 'interessment work' [START_REF] Callon | Some Elements of a Sociology of Translation: Domestication of the Scallops and the Fishermen of St Brieuc Bay[END_REF] done by the 4PM promoters had successfully translated into an actual enrolment. However, neither major agricultural emitting countries (the USA, Brazil, China, or Canada, to cite a few) nor a large part of civil society organisations initially interested in joining the 4PM did eventually sign up. To understand why, and to what extent this could affect the transformational potential of the initiative, we need to look at the strategies deployed by the promoters to interest each key actor.

What metrics and methods to control soil organic matter?

The obligatory passage point of the initiative being defined as an increase in soil organic matter, the question of its monitoring was a considerable stake for the promoters. Not the least because despite considerable progress in understanding soil carbon dynamics there are still considerable unknowns in this field and an objective of increasing soil organic carbon by 0.4% per year poses important challenges to soil scientists [START_REF] Baveye | The "4 per 1000" initiative: A credibility issue for the soil science community?[END_REF][START_REF] Dignac | Increasing soil carbon storage: mechanisms, effects of agricultural practices and proxies. A review[END_REF]Minasny et al., 2017b): the annual storage potential for soil organic carbon (SOC) first greatly varies according to types of soil, climate conditions and crop types, and is far from reaching 4‰ annually everywhere [START_REF] Lal | Beyond COP 21: Potential and challenges of the "4 per Thousand" initiative[END_REF]. Storing SOC can also lead to extra emissions elsewhere in particular due to stoichiometry problems: SOC can only be stored by simultaneously increasing levels of nitrogen, which is often achieved by adding mineral fertilisers whose production and application emits greenhouse gases (but see on that [START_REF] Soussana | Letter to the Editor: Answer to the Viewpoint "Sequestering Soil Organic Carbon: A Nitrogen Dilemma[END_REF]. SOC storage is also highly reversible, with the opposite change in practices potentially releasing as much CO2 as the initial change succeeded in storing. The measurement of stock variations over periods of less than five years also poses significant challenges, especially because the processes governing SOC dynamics are still poorly understood [START_REF] Dignac | Increasing soil carbon storage: mechanisms, effects of agricultural practices and proxies. A review[END_REF]. Despite these challenges, a suitable metric to follow this soil organic carbon increase was to be defined. It had to be a metric which would be consistent with the aim of the initiative, measurable with enough precision at an affordable cost in human and financial means, so as to be able to enrol countries with a low priority (and hence low budgets and human resources) on climate change mitigation: "These methods for estimating carbon stocks are a real stake. There is a scientific stake to be more precise, there is a political stake as well because for us, if we know that it increases and if we know that it increases of about 10%, that is enough for us, we do not really care about the difference between 9 and 11% from a political point of view. The political stake is, in particular in a lot of countries where these questions of mitigation are not a priority, to go and tell them to spend a lot of money in order to implement systems for estimating the evolution of carbon stocks". (a French civil servant in the 4PM project) Diverging views were expressed by pedologists and agronomists regarding the strategy to adopt in order to follow the increase in soil organic carbon: (i) adopting a stock-based approach, implying a cartography of soil carbon stocks in order to establish a baseline, and methods and tools to identify an increase in the stock; (ii) adopting a flow-based approach, using an assessment method that takes into account all entries and losses in greenhouse gases on an exploitation; (iii) whether based on stocks or flows, the metric could be based on the result in soil carbon stock increase or on the practices validated upfront as stocking soil carbon in certain pedoclimatic conditions. This latter point, in particular, was -and still is -the object of much controversy. Indeed, this point refers to the two-fold question of what is to be achieved by the initiative: Is the objective an increase in soil carbon per se, or the wider agricultural transformations it supposes and on which not all stakeholders necessarily agree? And what proxies to choose to measure progress? The small figure of 4‰ (0.4%) increase per year poses considerable methodological issues and source of scepticism regarding its feasibility. This is well illustrated by the following citation: "[It] would be much more easier to verify practices than to measure, on each hectare, how much carbon we stored: with a difference of 4 per 1000, it is a bit illusory to do it." (a French soil scientist involved in the 4 per 1000)

In addition to all these difficulties posed by the complexity of soils themselves [START_REF] Kon | Soil sciences and the French 4 per 1000 Initiative-The promises of underground carbon[END_REF], the 4PM promoters faced other challenges when they tried to enrol other actors in the initiative. Debates on the appropriate metric and monitoring system were then further nurtured during the months preceding COP21, and following requests to expand the scope of the initiative -in particular to fully cover the four pillars of food security defined by the FAO (availability, access, utilization, and stability).

States and international organisations

To get the interest of other countries, Le Foll's administration first relied on its diplomatic network. French embassies were asked to organize specific events in targeted countries to explain the objectives and the principles of the 4PM initiative. In this process, scientists were asked to help the administration in explaining further -when needed -the scientific foundations of the 4PM:

"What happened on December 1 st is the result of intense efforts by the French diplomatic network. And we contributed to it a little, for example, we organized a symposium in China, I have done a series of interventions in events which were linked to the activity of embassies in order to explain the programme and its scientific expectations". (a French scientist involved in the 4PM) More particularly, one key role played by scientists in this process was to shed light on the mostly technical approach adopted by the promoters, that is, the fact that many different agricultural practices and models were compatible with the 4PM target. One of the objectives was clearly to reassure specific countries (e.g., Brazil, China or the USA) on the fact that signing the 4PM declaration was not a commitment to engage towards a radical change of agricultural models: "We did not want to reduce '4 per 1000' to the sole promotion of agroecology because the idea is that other people could also recognize themselves in it and this is one of the differences which can be quite fundamental with some French NGOs, not all of them. […] We did not wish to restrain uniquely to agroecology, we think that there is progress which can be made in many systems, and that it can be interesting to put forward these kinds of experiences, when they are well documented and well monitored". (a French civil servant in the 4PM project) While this interessment strategy failed for many of the important countries that were initially targeted (among which the USA, Brazil and China), it nevertheless contributed to framing the initiative in a mere technical way. This had consequences on the capacity of the promoters to enrol other stakeholders, as we shall see below.

Before that, let us briefly address the case of the FAO. As the most important multilateral organisation for agriculture and food security, enrolling it was a key objective for the 4PM promoters. To say that this was easy would be to neglect two important objections brought by the FAO. The fact that the 4PM was initially seen as overly focused on mitigation, rather than on adaptation and food security; and the reliability of the 4‰ figure at the heart of the initiative. To answer such concerns, scientists were again mobilized, as well as the French Ambassador in Rome (where the headquarters of FAO are located). Most notably, this led the French administration to insist more on food security than was the case initially.

The challenge of enrolling NGOs

Insisting more on food security was also important with respect to on-going negotiations with civil society organisations, most of them being involved in the field of food and nutrition security. They were indeed quickly considered highly strategic targets for the 4PM promoters -both the administration and scientists -who remembered how civil society mobilisation was able to downplay the legitimacy of another multi-stakeholder initiative on the agricultureclimate nexus: the Global Alliance on Climate Smart Agriculture (see Stop GACSA, 2014).

Civil society organisations were thus consulted quite early in the process -as soon as May 2015. Their feedbacks were, however, considered as too radical by the 4PM promoters to be integrated directly in the initiative. The NGOs' main concern was the strong emphasis put on soil carbon sequestration which, for them, entailed three major drawbacks.

First, without sufficiently clear social and environmental safeguards, soil carbon sequestration could easily lead to any practices maximising soil carbon sequestration per unit of food produced to be "4PM compatible". Yet, there are several such practices that are considered to cause some environmental and social impacts. Conservation, or no-till, agriculture is often given as an example by NGOs: on the environmental side, no-till almost systematically relies on the use of herbicides that affect micro and macro soil biodiversity; on the social side, it often leads farmers to depend on "Round-up ready" GMO seeds and thus alter their financial and technical independence. Given this, most NGOs pushed for an approach that would go beyond the question of soil carbon sequestration and would expand to a discussion on agricultural models or systems. Some NGOs explicitly questioned some 4PM scientific promoters on that topic: "Concretely, I am expecting from research to be an ally of civil society to say to public authorities: 'Yes, soil organic matter is an interesting entry, but you should also take into account other criteria'. If the 4 per 1000 remains focalized on the question of stocking soil organic matter, we will not get very far." (a French NGO representative, during a workshop organized by IDDRI between NGOs and soil scientists)

The answer given to NGOs by scientists involved in 4PM was that their requests actually fell out of the scope of 4PM, and that it was not the role of soil scientists to enter into such a political debate.

Second, the focus on soil carbon sequestration was criticized by NGOs for leaving out, or at least downplaying, the many socio-economic, institutional, and political issues related to any change in agricultural practices, especially when oriented towards such a specific issue as sequestering carbon in soils: "Looking at soils as reservoirs of carbon, this is a very particular vision of the world […] [and I doubt] farmers from South and North see their agricultural soils this way. It would be interesting to mobilize the social and human sciences for this […]. Furthermore, it is important to remind that innovations are not necessarily technical, but also refer to organisational and institutional innovations. We have the impression that the focus is almost systematically put on the technical/technological question." (a French NGO representative, during a workshop organized by IDDRI between NGOs and soil scientists) Again, 4PM scientists were asked by NGOs to broaden the scope of the reflection. However, for most researchers involved in the 4PM being soil scientists or plant physiologists, questions such as land tenure rights, social representations of soils, the kinds of institutional framework needed to bring about changes in practices, etc., were obviously not usual questions for them. They generally seemed unable to answer such questions and contribute to discussions, seemed rather uninterested in doing so, and were not able to enrol social scientists who, in turn, would have probably been better equipped to address these questions.

Third, NGOs contend that the focus on soil carbon sequestration and its measurement entails the risk that, sooner or later, this carbon could be exchanged or sold on a voluntary market. This would allow large emitters in developing countries to compensate for their emission in Southern countries by investing in large-scale land rehabilitation projects [START_REF] Ccd & C2a | Initiative "4 pour 1000" : soyons vigilants ![END_REF]. Yet, such projects are said to be often associated with some forms of land grabbing.

They are also characteristic of fundamental asymmetries between Northern and Southern countries which these NGOs denounce.

On these three issues, the NGOs that eventually refused to sign up to for the 4PM judged answers from scientists as unsatisfactory. 4 In particular, they were highly critical towards the fact that, to them, policy-makers tended to use scientists as a way to legitimate the validity and legitimacy of their own initiative, while scientists refused to engage in more political discussions in the name of their neutrality:

"We have the feeling, that as time goes by, the political programme tends to hide more and more behind the scientific component. In other words, the political side does not acknowledge the risks and hides [itself] behind scientists, saying: we do not have all the answers but the scientists will give them to you later and it would remove the risks. We have sometimes the impression that politicians instrumentalize the scientists that you are, in order to avoid shouldering their responsibilities." (a French NGO representative during a workshop organised by the author between scientists and NGOs).

Two striking examples can be mentioned. The first one is in regards to the discussions that surrounded the development of a referential for the initiative -that is, a set of criteria and social and environmental safeguards that would serve to assess, ex-ante, in-itinere and ex-post the projects implemented as part of the 4PM initiative. While the authors of this text took a clear position on the need to define this referential as a way for the Scientific and Technical Committee (hereafter STC) to in/validate projects submitted to the 4PM initiative [START_REF] Treyer | Implementing the "4 per 1000" initiative: contribution for the establishment of a reference/ normative framework[END_REF], scientists composing STC refused to be given the authority to statute over a project, a role that was too political in their view.

The second example is the responses received by NGOs to their concerns, during the months following the announcement of the initiative: while NGOs had been asking "What is the 4 per 1000?", with concerns regarding the political framing and scope of the initiative, the answers given by promoters where channelled through presentations on the scientific basis behind the 4 per 1000 hypothesis:

"We now stand at our fourth scientific presentation, it is alright, we got that it is scientific, and we think it is a very good thing. Again, this could be a great opportunity for France to develop agroecology. Except that for all the questions we have been asking for five months, we never got the beginning of an attempt of a response, and these questions are actually still on the table." (a French NGO representative)

Discussion and conclusion

Over the last two decades, multistakeholder and voluntary partnerships have been more and more considered key vehicles for the implementation of international agreements for sustainable development, and more specifically the SDGs and the Paris Agreement (e.g. [START_REF] Beisheim | Multi-Stakeholder Partnerships for Implementing the 2030 Agenda: Improving Accountability and Transparency[END_REF]. However, the capacity of such partnerships to concretely deliver on their promises has been challenged by a series of research that have taken stock of previous initiatives (Szulecki et al., 2011 ;[START_REF] Biermann | The overall effects of partnerships for sustainable development: more smoke than fire?[END_REF][START_REF] Pattberg | Transnational multistakeholder partnerships for sustainable development: Conditions for success[END_REF].

One key question has remained underexplored so far. It concerns the way in which voluntary initiatives deal with the dual issue of being able to display a high level of ambition and clearly stated objectives, while still being able to enrol a wide range of stakeholders. In this paper, we have used the case of the 4PM to explore the knowledge dynamics at play and the role scientists could play to address both issues. We have shown that the emergence of the 4PM initiative has been marked by two types of collaboration between scientists and decision makers. On the one hand, during the launch phase of the 4PM, some scientists did not hesitate to minimize known uncertainties regarding the figures or the processes related to soil carbon sequestration, often in the name of being "policy relevant" while others criticised this posture.

On the other hand, and once the initiative had been effectively launched, scientists were, to some extent, used by the administration to fulfil certain tasks needed to interest, and then enrol, key and targeted actors. This has had three main consequences.

First, and in accordance with the strategy of the administration, soil scientists tended to keep the discussion with most stakeholders at a very technical level, this time in the name of their "neutrality". Second, this technical approach to soil carbon sequestration has probably helped to effectively interest some key players, and in particular States such as Germany, Australia, Argentina, New Zealand, or the Netherlands, although they are not totally aligned with the political vision put forth by Le Foll about the need for a radical agricultural model transition.

Third, while this technical approach was deemed to be apolitical, it was criticised for being, in fact, highly political in itself, as it has led to leave out of the scope most questions related to the transition of agricultural models. As a consequence, many NGOs did eventually not join the initiative.

The consequence of this "dual" positions of both the initiative and the scientists is that it did not manage to enrol neither large emitting countries that feared signing up for the 4PM would be too radical, nor civil society organisations representatives of peasant and familial agriculture that considered it as a way to "greenwash" existing practices for the benefit of dominant players. As such, the transformative potential of the initiative could have been questioned already in its early stages, though it is still too early to conclude on what the initiative will eventually be able to achieve.

A paper of the 4PM STC has recently been published, containing responses to several criticisms that have been raised over the last five years [START_REF] Rumpel | The 4p1000 initiative: Opportunities, limitations and challenges for implementing soil organic carbon sequestration as a sustainable development strategy[END_REF]. It is quite striking to see that virtually all of the criticisms that we describe here, on the lack of clarity of the 4PM initiative on its ambition for transforming agricultural models and addressing the four pillars of food security, are absent from the authors' discussion. They still mostly focus, as has been the case since 2015, on technical aspects of soil carbon dynamics and its assessment. The socioeconomic aspects are reduced to the incentives that could be provided to farmers. In the political aspects, only two issues are mentioned. The objection that the initiative is used to avoid question of "community lifestyles", to which the authors' answer is (still) that it is out of the 4PM scope. And criticisms over the fact that the lack of precision of the 0.4% objective is undermining the credibility of the soil science community (in other words, a debate that is still focused on soil carbon dynamics only).

We conclude by drawing four more general conclusions, regarding the role of scientists in the design and implementation of multistakeholder voluntary initiatives. Firstly, a large implication of scientists seems likely to reinforce the credibility of such initiatives, and could thus be promoted more widely. This would however only be fruitful if these initiatives are endowed with some budget to effectively support the work of researchers and their contribution to the initiative. Secondly, for scientists' implication to be truly successful, both for their own objectives and for the initiative to attract other stakeholders, scientists should also accept to fully discuss all the socio-economic and political implications of the different topics and objects they bring to bear in the policy process. When engaging in such a policy process, they should accept to be subjected to more accountability, especially on the framings that they impose or perpetuate (Jasanoff, 2003a).

Thirdly, a stronger cooperation between social and natural sciences is needed in order for scientists to (i) reinforce their capacity to effectively discuss the different implicationssocio-economic, political, and environmental -of their propositions and (ii) to strengthen their understanding of the strategic context in which they intervene (see in this volume Coreau).

Last but not least, this case study clearly illustrate the need to broaden the range of actors involved in the definition of an initiative, and not to restrict it to scientists and policy makers alone. As for most other issues of contemporary life, "technologies of humility" (Jasanoff, 2003b[START_REF] Jasanoff | Technologies of humility[END_REF] are needed, notably so that more voices are included in how we frame issues.

It is hard to tell whether the 4PM initiative would have had more successful outcomes, had its promoters managed to integrate more perspectives at the onset. However, the early framing of the initiative, which still prevails, clearly seems to have locked it into the very same issues that it faced in its early stages. The central bet of its political promoters, which was to push for transforming global agricultural models while "hiding" behind a focus on soil organic carbon, has neither enabled to enrol the actors that are the most recalcitrant to such changes, nor the actors that could have been powerful allies in carrying the initiative further. What could well have been lost, in the meantime, is yet another opportunity to raise the profile of the much needed international conversation on how to move away from productivist models of agriculture, which (almost) everyone agreed already quite some years ago that "there are no longer an option" (McIntyre et al., 2009). 5 used by scientists to make their work count in policy arenas, with the ultimate goal of finding potentially more potent ways for scientists to support environmental policy. He holds a PhD in ecology (Sorbonne Université) and a master in international affairs (Sciences Po Paris).

  4PM initiative: agriculture to save climate... or climate to save agriculture?

Figure 1 :

 1 Figure 1: The increase in soil organic carbon stocks, an obligatory passage point for the

Including 42 countries and regions, 12 international organizations, 14 foundations and development banks, 110 Non-governmental organizations, 80 research and teaching institutes, 40 farmers' organizations, and 61 private companies. See: https://www.4p1000.org/governance (last consulted 5 June

2020).

See in that respect the manifesto signed by more than

civil society organizations saying stop to GACSA: http://www.climatesmartagconcerns.info/francais.html

The remainder of the paper focuses on the action programme of the

4PM and how scientist had been asked to contribute to it, besides their involvement in the scientific part.

It must however be noted that more than 100 NGOs to date joined the 4 per 1000 initiative, some of them defining themselves as "critical friends" of the initiative. They are mostly interested in the potential of the 4PM to promote more widely agroecological practices and models. They also consider, contrary to the vast majority of CSOs who did not join the initiative, that despite the many uncertainties, it is worth trying rather than doing nothing.

The USA, Canada, and Australia did not endorse the International Assessment of Agricultural Knowledge, Science and Technology for Development.

Acknowledgements

This article is based on research that has received a financial support from the French government in the framework of the programme « Investissements d'avenir », managed by ANR (French national agency for research) under the reference ANR-10-LABX-14-01. We warmly thank two anonymous reviewers for their useful comments that helped us improve the manuscript.

Conflicts of interest

The authors declare no conflict of interest.

Stop GACSA (2014). Why we reject the Global Alliance on Climate Smart Agriculture. Szulecki K., Pattberg P. & Biermann F. (2011). Explaining Variation in the Effectiveness of Transnational Energy Partnerships. Governance, 24 (4), 713-736. VandenBygaart A. (2017). Comments on soil carbon 4 per mille by Minasny et al. 2017. Geoderma. White R.E., Davidson B., Lam S.K., et al. (2017). A critique of the paper 'Soil carbon 4 per mille'by Minasny et al.(2017). Geoderma.

Biographies

Pierre-Marie Aubert is the head of the Agriculture initiative at IDDRI. He works on two main topics: the formulation, evolution and evaluation of public policies at multiple levels in the field of agriculture, food security and natural resources management; and the governance and sustainability of agri-food chains. He had been working on forestry and environmental policies in Northern Africa for 6 years. Since 2015, his work focuses on European agriculture and food policies and their role in fostering an agro-ecological transition across Europe. Rémy Ruat is a graduate in environmental sciences and policies from Sciences Po and the University Pierre et Marie Curie. His activities so far have focused on the role of non-state actors (businesses, cities, NGOs and scientists) in national and international climate policies, as well as on environmental accounting and its link with public policies. Sébastien Treyer is the general director of IDDRI. His research focuses on three fields of environmental policies: the design of foresights and forward-looking processes for long-term water resources management; the use of foresights at various steps and for various levels of the protection of ecosystems; and the role played by scenarios as central elements of expertise for global environmental governance. Aleksandar Rankovic is a researcher at IDDRI, where his work addresses the interactions between environmental sciences and policies. He combines theoretical frameworks from science and technology studies and strategic analysis to analyse and discuss the strategies