The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on post-operative outcome

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The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on post-operative outcome A. Michot a, E. Stoeckle a,*, J.-D. Bannel b, S. Colombani c, P. Sargos d, V. Brouste e, A. Italiano f, M. Kind g a

Department of Surgery, Institut Bergonie, 229 cours de l’Argonne, F-33076 Bordeaux, France b Department of Physiotherapy and Re-education, Institut Bergonie, 229 cours de l’Argonne, F-33076 Bordeaux, France c Department of Anaesthesia and Reanimation, Institut Bergonie, 229 cours de l’Argonne, F-33076 Bordeaux, France d Department of Radiotherapy, Institut Bergonie, 229 cours de l’Argonne, F-33076 Bordeaux, France e Clinical and Epidemiological Research Unit, Institut Bergonie, 229 cours de l’Argonne, F-33076 Bordeaux, France f Department of Medical Oncology, Institut Bergonie, 229 cours de l’Argonne, F-33076 Bordeaux, France g Department of Medical Imaging, Institut Bergonie, 229 cours de l’Argonne, F-33076 Bordeaux, France Accepted 25 August 2015 Available online - - -

Abstract Background: Enhanced recovery after surgery (ERAS) programs are implemented in multiple fields of surgery, but not yet in soft-tissue sarcoma (STS) surgery. We wondered whether its introduction into STS surgery might have impacted postoperative outcome. Methods: Two hundred and fifty seven adult patients with primary limb or trunk wall STS received ERAS from 2008 to 2012 as a part of the intra-operative management. We evaluated, in retrospect, the intra-operative management, post-operative outcomes, functional and oncological results of these patients and compared them with 459 prior patients treated under a standard recovery after surgery (SRAS) program from 1989 to 2007. Results: The most visible change from SRAS to ERAS in the perioperative management was decrease of wound drainage (72% vs. 15%, p < 0.001) and increase of wound bandaging (16% vs. 66%; p < 0.001), underlining the appliance of the ERAS protocol. Post-operatively, hospital stay dropped from nine (0e74) to three (0e22) days (p < 0.001) without affecting major morbidity (8% vs. 5%, NS) or readmission to the hospital (5% vs. 4%, NS). Functional outcome improved (p ¼ 0.009) but whether this change was due to ERAS remains to be proved because complementary treatments changed over time. Tumour control remained unaffected, with an estimated risk of local recurrence at 5 years of 12% in both groups. Conclusion: Introducing a rapid recovery program was associated with a shorter hospitalization stay without compromising surgical or oncological outcomes. The program appears to be safe and reliable to use in patients undergoing STS surgery. Ó 2015 Elsevier Ltd. All rights reserved.

Keywords: Enhanced recovery after surgery; Fast-track; Soft-tissue sarcoma; Surgery; Morbidity; Functional outcome

Introduction Programs for early rehabilitation or enhanced recovery after surgery (ERAS) are widely applied in bowel,1 * Corresponding author. E-mail address: [email protected] (E. Stoeckle).

orthopaedic,2 gynaecologic cancer,3,4 and liver surgeries.5 These programs consistently report reductions in postoperative pain,6 a significant drop in post-operative morbidity, convalescence time and length of stay (LOS) at hospital.1,7 Soft-tissue sarcoma (STS), mainly located in the extremities or the trunk wall, are treated by limbsparing surgery, usually completed by radiotherapy.8 Most

http://dx.doi.org/10.1016/j.ejso.2015.08.173 0748-7983/Ó 2015 Elsevier Ltd. All rights reserved. Please cite this article in press as: Michot A, et al., The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on postoperative outcome, Eur J Surg Oncol (2015), http://dx.doi.org/10.1016/j.ejso.2015.08.173

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A. Michot et al. / EJSO xx (2015) 1e7

studies in STS surgery have focused on oncological outcomes9,10 or morbidity and functional outcome,11 but to our knowledge, no study on early rehabilitation in STS surgery has yet been published. At the Institut Bergonie, we introduced limb-sparing surgery for STS in 1975.12 The abandonment of radical surgery (amputation and compartmental resection) prompted us to define criteria for resection quality within the new multidisciplinary treatment approach. It was done in the frame of the French Sarcoma Group (GSF-GETO).13 We evaluated those defined resection quality criteria on successive patient groups from our institution, showing that they were reliable14 and predictive for oncological outcome.15 Oncological results compared favourably to literature data making such a conservative surgery within a multidisciplinary approach standard of care in our center.16 However, hospital care revealed unsatisfactory with prolonged LOS, favoured by persisting wound drainages and lack of patient autonomy. We consequently introduced changes in the perioperative patient care with successive changes in drainage techniques and finally their abandon, replacing drainage by compressive bandaging (wrapping). Concomitantly we introduced better pain control through loco-regional analgesia and early ambulation. After a transition period from 2004 to 2007 and with the arrival of a physiotherapist, we introduced a formal program for ERAS in 2008. The aim of this study is to evaluate whether this program revealed to be safe in patients operated for primary limb and trunk wall STS in terms of post-operative morbidity and late functional outcome. Methods Patient selection and treatment periods After institutional review board approval, patient charts were extracted and cross-checked from both our institutional database for STS surgery and Conticabase, an international sarcoma database, including tumour and treatment characteristics of patients treated at our Institute. Adult patients (16 years) with primary non-metastatic STS located in the trunk wall or the limbs that were operated at Institut Bergonie between 1989 and 2012 were included in the study. We then compared patient outcomes from the ERAS period (2008e2012) to the prior standard recovery after surgery (SRAS) period (1989e2007).

detailed information about the surgical program and preventive measures (e.g. re-nutrition after weight loss) were taken. Sugary drinks were allowed up to two hours prior to anaesthesia. Compressive stockings were put on, but no thrombo-prophylactic medicines were given. Neither prophylactic antibiotics were given nor was a urinary catheter set. During surgery, general anaesthesia was complemented by administering a loco-regional analgesic for pain prevention. We avoided tourniquets in order to prevent ischaemia, and performed a gentle tissue-, nerve- and vessel-sparing dissection. We used tension-free wound closure, or if needed tissue flaps. Wound drainage was omitted whenever possible and in order to avoid dead spaces favouring fluid collections, a compressive bandaging (wrapping) was applied mainly to extremity sarcoma, whereas stitches securing the skin to underlying tissues were applied mainly to trunk wall sarcoma. Exceptions for maintaining drainage were particularly difficult dissections with huge tissue losses or specific locations making a bandage difficult to pose. No splint was set-up, allowing the joints to move freely. No patient stayed in the intensive care unit (ICU). Loco-regional analgesics were continued post-operatively, and subsequently replaced by oral analgesics. The role of the physiotherapist was crucial in helping the patients to reacquire their autonomy in the postoperative period. By his reassurance and technical support he helped them to retrieve confidence, allowing them to move their body without pain and walk around as early as day 0. The bandages were removed after day 1 and the dressing after day 2, leaving the suture open thereafter (Fig. 1). The patients were allowed to have showers. Stockings were kept until the patients were discharged. The patients were discharged as soon as they were able to walk autonomously without pain. After discharge, patients were advised to continue with the apprised self-reeducation technique, but physiotherapy was not prescribed, in order not to hamper wound healing during the first four post-operative weeks. Oral analgesics, mainly paracetamol completed by tramadol if needed, were continued for few days with no other medical treatment. A post-operative visit was organized four weeks after surgery. In the event of a complication, especially seroma formation, patients were advised to contact our outpatient consultation unit for drainage. Information was provided verbally and no written patient consent was required. Multidisciplinary treatment and follow-up

Surgery and the ERAS program The oncological aim of surgery was resection according GSF-GETO principles13e15 which remained unchanged over time. In contrast, from 2008 onwards, we systematically adapted ERAS measures from recommendations of the ERASÒ pathway of the ERAS society to limb and trunk wall STS. They comprised pre-, intra-, and post-operative measures. Prior to the operation, the patients were given

Treatment protocols during the time period foresaw postoperative external beam radiotherapy in patients with deep STS of the limbs or trunk wall. A 50 Gy dose was prescribed, completed by a boost after R1 resections.14,17 In the beginning of the period patients with high-grade tumours received adjuvant chemotherapy, based on combinations with doxorubicin. Following multidisciplinary decision, patients with locally advanced high-grade tumours received pre-operative neo-

Please cite this article in press as: Michot A, et al., The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on postoperative outcome, Eur J Surg Oncol (2015), http://dx.doi.org/10.1016/j.ejso.2015.08.173

A. Michot et al. / EJSO xx (2015) 1e7

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Figure 1. A thirty year old woman presenting with a 15 cm myxoid liposarcoma of the posterior thigh. A: incision; B: surgery, no tourniquet; C: wrapping, no drain; D: post-operative walking day 1.

adjuvant intravenous combination chemotherapy. In 12 patients (8 SRAS, 4 ERAS) neo-adjuvant treatment was performed by isolated limb perfusion with TNF and melphalan. All those patients received post-operative radiotherapy. Preoperative radiotherapy was not given at that time period. After treatment, patients were regularly followed-up at the clinic with a physical examination of the tumour bed and a chest X-ray. The rhythm of follow-up was every four months during three years, than every six months during two years and then annually. Follow-up was alternately performed by the surgeon, the radiotherapist and the oncologist. Patient characteristics and variables for outcome Patient and tumour characteristics were retrieved from Conticabase where tumour pathology is collegially reviewed before inclusion in the database. Quality of resections were determined according to UICC resection (R) categories and classified according to the French Sarcoma Group (GSF-GETO) into R0 (in sano), R1 (possible microscopic residual disease), and R2 (macroscopic residual disease) categories.13e16 Surgical data, including prior surgery outside of our institution, the place of surgery in the treatment sequence, wound drainage, wrapping, LOS, morbidity and functional outcomes were retrospectively retrieved from individual patient charts by one of the authors (AM). Morbidity was classified into 6 types: lymphorrhea/seroma, bleeding/hematoma, infection/abscess, wound dehiscence/complications, deep vein thrombosis/pulmonary embolism and other, and graded according to the ClavieneDindo scale.18 In order to obtain easily distinguishable groups, we defined and retained only two categories of morbidity: minor (Grade 1 and 2) and major (Grade 3 and 4). Prior appreciations of functional outcome using LENT SOMA and Enneking scoring19 showed difficult to be applied after multidisciplinary

treatment and were not maintained for further functional evaluation. Consequently, we subdivided the retrospectively yielded functional outcome data into two easily distinguishable categories: 1) good outcome (excellent/good results with minor discomfort/pain) and 2) poor outcome that combines fair (moderate limitations of movement or pain requiring treatment) and poor (permanent discomfort or incapacity with need of a support to compensate a loss of function) results. Functional outcome was evaluated regularly during follow-up. In order to determine final functional outcome, overseeing temporary post-therapeutic functional impairment, we retained the combined results of the last three follow-up results for analysis. We were able to determine the functional outcome for 723 patients (99%). Statistics and follow-up Categorical variables are expressed as counts and percentages, whereas numerical variables are expressed as median (range) or mean (standard deviation). Categorical variables were compared with the Chi-square test or Fischer’s test. Numerical variables were compared with the nonparametric Wilcoxon test or the Student test according to their distribution. Follow-up was calculated with the reverse KaplaneMeier method. Overall survival (OS) was calculated with the KaplaneMeier method from the date of initial diagnosis to the date of death from any cause, and patients alive were censored on the date of the last follow-up. Metastatic-free survival (MFS) and local recurrence-free survival (LRFS) were initially estimated by the KaplaneMeier method, and then with the competitive-risk method which considered both death without metastases or without local recurrences a competitive risk. For all analyses, p < 0.05 was considered as significant. Data analysis was performed with the SPSS 20.0 software (SPSS Inc., Chicago, IL, USA).

Please cite this article in press as: Michot A, et al., The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on postoperative outcome, Eur J Surg Oncol (2015), http://dx.doi.org/10.1016/j.ejso.2015.08.173

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A. Michot et al. / EJSO xx (2015) 1e7 Table 2 Intra-operative management and complementary treatment for patients receiving either standard recovery after surgery (SRAS) or enhanced recovery after surgery (ERAS) programs for limb and trunk wall softtissue sarcoma (STS).

Results Patient and treatment characteristics Out of the 734 patients that were included in the study, 459 were treated under SRAS and 275 under ERAS. The patient and tumour characteristics are depicted in Table 1. Some differences between groups emerge: ERAS patients were older, had smaller tumours (70 mm vs. 80 mm), which were more often superficial (30% vs. 17%) and less frequently high grade (Table 1). The gender repartition, tumour location and histology were comparable between groups. Timing of surgery, the importance of reconstructive surgery and quality of resection were similar, but SRAS patients received more reconstructive surgery than ERAS patients (15% vs. 9%, p ¼ 0.01). Adjuvant chemotherapy or post-operative radiotherapy were less frequently used during ERAS, but the rate of neo-adjuvant chemotherapy remained stable (Table 2). According prescription changes in wound management, wound drainage decreased from 72% to 15% (p < 0.001) and wrapping increased from 16% to 66% (p < 0.001; Table 2).

Table 1 Patient and tumour characteristics for patients receiving either standard recovery after surgery (SRAS) or enhanced recovery after surgery (ERAS) programs for limb and trunk wall soft-tissue sarcoma (STS). SRAS period N ¼ 459 (%) Mean age in years (SD) Sex Female Male Localization Shoulder girdle Upper limb Trunk wall Pelvic girdle Lower limb Size Median in mm (range) Tumour depth Superficial Deep Histological subtypes Undifferentiated sarcoma Muscular sarcoma (LMS þ RMS) Other LPS Myxoid LPS Synovial Sarcoma Others Grade 1 2 3 N/A

55 (17)

ERAS period N ¼ 275 (%) 58 (18)

223 (49) 236 (51)

126 (46) 149 (54)

30 51 76 40 262

18 31 46 32 148

0.04 NS

(6) (11) (17) (12) (54) 0.001

80 (8e600)

70 (10e480) <0.001

77 (17) 382 (83)

83 (30) 192 (70)

121 (26)

84 (31)

84 (18)

45 (16)

70 48 39 97

(15) (10) (9) (21)

55 23 11 57

(20) (8) (4) (20)

108 125 216 10

(24) (27) (47) (2)

75 92 95 13

(27) (34) (34) (5)

ERAS period N ¼ 275 (%)

349 (76) 110 (24) 69 (15)

205 (75) 70 (25) 24 (9)

330 (72) 129 (28)

41 (15) 234 (85)

p-Value NS

0.01 <0.001 <0.001

74 (16) 385 (84)

181 (66) 94 (34)

316 (69) 140 (30) 3 (1)

186 (68) 89 (32) 0 (0)

20 (4) 349 (76) 50 (10e70)

11 (4) 162 (59) 50 (42e65)

NS

103 (22) 121 (26)

19 (7) 83 (30)

NS <0.001 NS <0.001 NS

p-Value

NS (6) (11) (17) (9) (57)

Timing of surgery First Second/third Reconstructive surgery Wound management Drainage Yes No Wound compression/wrapping Yes No Resection quality R0 R1 R2 Radiotherapy Prior history of radiotherapy Post-operative radiotherapy Median dose in Gy (range) Chemotherapy Adjuvant Neo-adjuvant

SRAS period N ¼ 459 (%)

Post-operative outcome LOS decreased significantly from nine (0e74) to three days (0e22;p < 0.001; Table 3, Fig. 2). There was no change in overall morbidity (42% vs. 36%), nor mostly in any individual complications between the SRAS and the ERAS group. Major morbidity diminished insignificantly from 8% to 5% and re-admission to the hospital remained unchanged (5% vs. 4%; Table 3). ERAS patients had a better functional outcome than SRAS patients with 94% vs. 89% of good results (p ¼ 0.009; Table 3).

NS

Follow-up and oncological outcomes

0.009

Median follow-up was 91 months (95% CI: 80e100) in the whole group, 140 months (95% CI: 128e149) in the SRAS period and 40 months (95% CI: 37e42) in the ERAS period. For the entire population, OS at 5 years was estimated as 80% (95% CI: 77e83) and the risk of local recurrence at 5 years was 12% (95% CI: 9.7e14.8). Using competitive risk analysis to compare the SRAS to the ERAS period, OS was estimated 79% vs. 81% (NS), the risk of metastases 20% (95% CI: 16.7e24.2) versus 18% (95% CI: 11.5e26.2; NS), and the risk of local recurrence was 12% (95% CI: 9.2e15.3) versus 12% (95% CI: 8.5e17.8; NS).

Abbreviations: LMS: leiomyosarcoma; RMS: rhabdomyosarcoma; LPS: liposarcoma; N/A: not applicable.

Please cite this article in press as: Michot A, et al., The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on postoperative outcome, Eur J Surg Oncol (2015), http://dx.doi.org/10.1016/j.ejso.2015.08.173

A. Michot et al. / EJSO xx (2015) 1e7 Table 3 Post-operative outcome for patients receiving either standard recovery after surgery (SRAS) or enhanced recovery after surgery (ERAS) programs for limb and trunk wall soft-tissue sarcoma (STS). SRAS period N ¼ 459 (%) Median length of stay (range) Post-operative complications Minor Major Type of complicationa Seroma formation Wound dehiscence/complication Infection/abscess Hematoma/bleeding Other DVT/PE Hospital readmission Functional outcome Excellent Good Fair Poor Incapacity NE/A Excellent þ Good Fair þ Poor þ Incapacity

9 (0e74)

ERAS period N ¼ 275 (%)

p-value

3 (0e22)

<0.001 NS

156 (34) 37 (8)

85 (31) 15 (5)

99 (22) 93 (20)

61 (22) 45 (16)

NS NS

41 27 23 7 25

(9) (6) (5) (2) (5)

15 (6) 9 (3) 4 (1) 2 (1) 11 (4)

NS NS 0.01 NS NS

238 162 33 5 13 8 400 51

(52) (35) (7) (1) (3) (2) (89) (11)

162 (59) 95 (35) 11 (4) 0 4 (1) 3 (1) 257 (94) 15 (6)

0.009

DVT/PE: deep vein thrombosis/pulmonary embolism. NE/A not evaluable/applicable. a A patient may cumulate several complications.

Exploratory subgroup analyses Due to the differences in tumour characteristics between periods, with more superficial and smaller tumours in the ERAS period, we investigated outcomes for the deep

Figure 2. Graph illustrating the change in length of stay (LOS) at hospital from a median of 9 days during the standard recovery after surgery (SRAS) period (1989e2003) to a median of 3 days during the enhanced recovery after surgery (ERAS) period (2008e2012). Note the shorter day intervals in the intermediate period from 2004 to 2007 at which several ERAS measures where successively applied translating into the shortening of LOS and day intervals.

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tumours only subgroup. Overall, 574 deep tumours were included: 382 SRAS and 192 ERAS. For these deep tumours, the age difference (55 vs. 57 years, p ¼ 0.16) and the size difference (100 vs. 90 mm, p ¼ 0.5) disappeared and the grade difference became less pronounced (p ¼ 0.04). In terms of intra-operative management, the reductions observed in drainage, and increase in wrapping were maintained (p < 0.001 in both), morbidity did not change and the drop in LOS previously observed was supported with a reduction from 10 to 4 days (p < 0.0001). Post-operative radiotherapy was delivered respectively to 88% and 76% of the patients (p < 0.001). Improvements in functional outcome were maintained (p ¼ 0.04). Discussion In this longitudinal study we observe that LOS dropped dramatically from nine to three days after the introduction of ERAS to STS of the limbs or trunk wall. Remembering that LOS was determined by strict discharge criteria, its change after the introduction of this voluntarily ERAS program suggest a causal relationship between ERAS and LOS. Differences in tumour characteristics may have influenced LOS, but the same drop in LOS is also observed in the subgroup of deep tumours which bear similar characteristics. Furthermore, as demonstrated in Fig. 2, LOS decreased to intermediate lengths of six days during the transition period (2004e2007) where partial ERAS measures were tested, strengthening our hypothesis of a direct relationship between LOS and ERAS. Having introduced ERAS and observed a major reduction of LOS, we did not find any negative impact on post-operative outcome through ERAS with similar morbidity rates between the standard and the ERAS period (42% vs. 36%). Moreover, re-hospitalisation rates (5% vs. 4%) remained unchanged between periods, underlining the feasibility and reliability of this ERAS program in STS. The possible impact of complementary treatments on post-operative outcome can be ruled out: postoperative radiotherapy, less frequent in the ERAS period, could not have affected outcome because it was delivered after complete wound healing only; neo-adjuvant chemotherapy, on its side, was equally departed between patient groups (26% vs. 30%, Table 2). Contrarily to our expectations, post-operative seroma formation did not decrease with the application of ERAS measures. Seroma formation remained remarkably stable with a rate of 22% in both patient groups (Table 3). Nevertheless, seroma formation did not prevent ERAS patients from being discharged earlier. Likewise, in breast surgery, the absence of drainage did not increase seroma formation and allowed earlier discharge.20 Moreover, with the containment of dead spaces by stitches or wrapping a trend to fewer bleeding or occurrence of hematoma appeared (from 6% to 3%; Table 3). Similarly in hip replacement, a study comparing drainage to bandaging showed

Please cite this article in press as: Michot A, et al., The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on postoperative outcome, Eur J Surg Oncol (2015), http://dx.doi.org/10.1016/j.ejso.2015.08.173

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A. Michot et al. / EJSO xx (2015) 1e7

that the latter group needed significantly fewer transfusions and that the patients had fewer wound complications.21 Globally, it appeared that the abandon of drainage did not unfavourably impact our patients’ outcome. Another deception was the absence of a significant reduction in major morbidity as usually observed with ERAS programs in abdominal surgery. This fact may be explained in our STS patients by the absence of ICU stay prone to favour medical complications (e.g. infections, respiratory diseases, embolisms). When taking into account nonsurgical complications (“other” þ DVT/PE) their incidence decreased from 7% (30 patients) to 2% (6 patients) within our groups (Table 3). Moreover, with an already low major morbidity rate of 8% in the standard recovery group, obtaining 5% in the ERAS group can be considered as clinically relevant, even if the difference remains insignificant. Both rates compare favourable to what is observed in other series of patients with limb and trunk STS receiving multidisciplinary treatments. In the Canadian trial comparing pre-to post-operative radiotherapy, major morbidity were 35% and 17% in each treatment arm, respectively.22 Major post-operative morbidity reached 32% and 35% in other series with pre-operative radiotherapy.23,24 Compared to our findings in the post-operative setting, the concept of pre-operative radiotherapy in STS patients is challenged by its high morbidity rates. Functional outcome improved from 89% good/excellent results to 94% through the two periods (Table 3). Logically, early rehabilitation should have contributed to this progress. However, post-operative radiotherapy that might have negatively impacted function was more frequently delivered to SRAS than to ERAS patients (76% vs. 59%). The respective impacts of either ERAS or post-operative radiotherapy on functional outcome in this patient group therefore could not be determined. However, we expect a lesser negative impact of post-operative radiotherapy on functional outcome in our patient group compared to that seen in the Canadian trial because of the lower dose of radiotherapy (50 Gy vs. 66 Gy).22

necrosis, a major component of the French Grading System, is less present in CNB specimen.25 This lack could not be corrected secondarily with the analysis of the entire tumour specimen in the 30% of ERAS patients receiving neoadjuvant chemotherapy. Our hypothesis that grade, a major prognostic factor in STS, did not differ between groups is comforted by the observation that oncological outcomes, i.e. survival, metastases and local recurrences were the same in both groups, in line with other reports.9,10,26 Concerning the other tumour characteristics, their differences disappeared within the deep tumour subgroups. 2.) The retrospective retrieval of outcome data. As noticed, they were registered by different physicians during followup, smoothening differences in appreciation of outcome. All retrospective data were compiled by a single person (AM) homogenising outcome data description. To minimize confusion between categories, only two categories were established for morbidity and functional outcome. Taken together, these measures allowed not to refine the appreciation of functional outcome, but to give a robust and reproducible appreciation between good and poor outcome. In conclusion, in our patients with STS undergoing surgery first, the implementation of an ERAS protocol offered shorter LOS without compromising post-operative outcome. We now propose it to selected patients on an in-day basis. Whether this ERAS program can be transposed to protocols with pre-operative radiotherapy should be evaluated.

Limitations and strengths

The authors thank Pippa McKelvie-Sebileau and Ravi Nookala of Institut Bergonie for help with writing this manuscript.

We report about outcome in a consecutive series of patients treated in a single institution by a constant group of sarcoma specialist with merely unchanged treatment protocols applied over this long time span. This homogeneity is the strength of our series. There are two limitations: 1.) Patient characteristics changed over time and, accordingly, complementary treatment. The difference in tumour grade was the most important factor, with especially more grade 2 and less grade 3 tumours in the ERAS period. However, this difference may be an artificial one: biopsy was performed mainly surgically in the standard recovery, whereas core needle biopsy (CNB) was done in the ERAS period. However, CNB underestimates the tumour grade because

Disclosures The authors received no financial support for this study. Conflict of interest statement All authors declare that there was no conflict of interest with the purpose of the present work.

Acknowledgements

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Please cite this article in press as: Michot A, et al., The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on postoperative outcome, Eur J Surg Oncol (2015), http://dx.doi.org/10.1016/j.ejso.2015.08.173