UvA-DARE (Digital Academic Repository) Optimisation of surgical care for rectal cancer Borstlap, W.A.A. Link to publication

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1 UvA-DARE (Digital Academic Repository) Optimisation of surgical care for rectal cancer Borstlap, W.A.A. Link to publication Citation for published version (APA): Borstlap, W. A. A. (2017). Optimisation of surgical care for rectal cancer General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 02 Jan 2018

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3 Optimisation of surgical care for rectal cancer

4 Lay-out Gildeprint, Enschede Printing Gildeprint, Enschede ISBN: Copyright Wernard A.A. Borstlap. No parts of this thesis may be produced, stored, or transmited in any form by any means, without prior permission of the author. Financial support for the printing of this thesis was kindly provided by: Chipshoft B.V., B.Braun Medical B.V., Vifor Pharma B.V., Nederlandse Vereniging voor Gastroenterologie, Wetenschapsbureau Tergooi Ziekenhuis, Wetenschappelijk Fonds Chirurgie AMC

5 Optimisation of surgical care for rectal cancer ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. ir. K.I.J. Maex ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op vrijdag 3 november 2017, te uur door Wernard Aat Antoine Borstlap geboren te Nijmegen

6 Promotiecommissie Promotor: Prof. dr. W.A. Bemelman AMC - Universiteit van Amsterdam Copromotores: Dr. P.J. Tanis Dr. J.B. Tuynman AMC - Universiteit van Amsterdam Vrije Universiteit Amsterdam Overige leden: Prof. dr. M.A. Boermeester Prof. dr. O.M. van Delden Prof. dr. C.A.M. Marijnen Dr. C.I.J. Ponsioen Prof. dr. J.H.W. de Wilt AMC - Universiteit van Amsterdam AMC - Universiteit van Amsterdam Universiteit Leiden AMC - Universiteit van Amsterdam Radboud Universiteit Nijmegen Faculteit der Geneeskunde

7 Contents General Introduction and outline of the thesis 7 Part I - Preoperative optimisation of colorectal cancer patients: Chapter 1 - Chapter 2 - Preoperative iron therapy for reducing anaemia in patients with a colorectal carcinoma; a systematic review. Multicentre randomized controlled trial comparing Ferric(III) carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients Part II - Minimally invasive treatment strategies for early rectal cancer: Chapter 3 - Chapter 4 - Chapter 5 - Chapter 6 - Systematic review and meta-analysis of oncological outcome after local excision of pt1-2 rectal cancer with adjuvant (chemo)radiotherapy compared to completion TME surgery. A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer. Resection of rectal tumours: Natural course after transanal endoscopic microsurgery (TEM) without total mesorectal excision (TME) for T2 and T3 rectal carcinoma. Guideline Synopsis: rectal preserving treatment options for early rectal cancer

8 Part III - Complications following rectal surgery: Chapter 7 - Complications following rectal surgery. 139 Chapter 8 - Chapter 9 - Benchmarking recent national practice in rectal cancer treatment with landmark randomized controlled trials Anastomotic leakage and chronic presacral sinus formation after low anterior resection, results from a large crosssectional study. Chapter 10 - Hospital variation in surgical strategy of low anterior resection for rectal cancer with respect to temporary and permanent stoma rate. Chapter 11 - Vacuum assisted early transanal closure of leaking low colorectal anastomoses, the CLEAN-study. Chapter 12 - Feasibility and short term outcome of the TAMIS-technique for redo pelvic surgery. Chapter 13 - Intersphincteric completion proctectomy with omentoplasty for chronic presacral sinus after low anterior resection for rectal cancer Appendices Summary and future perspectives 283 Samenvatting en toekomstperspectieven 289 PhD Portofolio 298 List of publications 300 Dankwoord 304 Curriculum Vitae 308

9 General Introduction Colorectal cancer has become the second most common cancer in the Netherlands with approximately new cases every year. 1,2 Numerous innovations in the last decades have significantly improved the prognosis of colorectal cancer in terms of survival, cancer recurrence and treatment related morbidity. 3,4 Current treatment strategies have a multimodal character involving multiple specialities, in which surgical resection remains the cornerstone of a curative treatment. An important benefit of this multimodal approach of colorectal cancer patients is that it stimulates the physicians to look further than their own speciality. As a consequence, preoperative optimisation of the patient prior to surgery has gained more attention. The waiting time from diagnosis to surgery (commonly 4-6 weeks) could be seen as a window of opportunity to enhance the physical status of the patient in the work-up towards surgery. 5 Due to differences in biology, prognosis, treatment strategies and treatment related complications cancer of the colon and rectum should be seen as two different entities. This thesis mainly focusses on the optimisation of surgical care of cancer located in the rectum, which is the case in approximately a third of all colorectal cancers. 6 Early in the nineteen eighties, surgical resection of the rectum underwent a major development due to the introduction of complete resection of the visceral mesentery en-bloc with the rectum, the total mesorectal excision (TME). The original paper of Heald published in 1986, showed that with the addition of TME, local recurrence rates less than 4% could be achieved. 7 Previously recurrence rates of up to 30-40% were common. For this reason TME and clear resection margins became the basic principles of a proper resection for rectal carcinoma. Due to the recent introduction of screening programs, there is a shift towards the detection of earlier stage cancers. Detection at an earlier stage potentially allows for less invasive treatment strategies. Very early cancers are commonly defined as T1, SM1, well differentiatied, no lymphatic and no venous invasion, and <3cm in size. These cancers have an excellent prognosis and can be treated with local endoluminal excision, thereby preserving the rectum. 8 With endoluminal techniques as snare polypectomy, endoscopic submucosal dissection, or transanal endoscopic microsurgery (TEM), the rectum stays in situ, and therefore these procedures are 7

10 General Introduction associated with less morbidity, better functionality and it spares the patient from the risk of receiving a stoma when compared to TME surgery. Also for the early stage cancers with less favourable characteristics, rectal preserving strategies are currently being evaluated. A curative treatment strategy of early staged rectal cancer with preservation of the rectum by using either neoadjuvant or adjuvant (chemo)radiotherapy in combination with or without local excision seems possible, however the exact boundaries of these treatment strategies are yet to be defined. Therefore, TME surgery is still considered the gold standard for rectal cancer other than low risk T1 stage. The downside of surgery that included resection of the rectum, is the relatively high risk of postoperative complications, with even a small risk of mortality. Furthermore, there is a substantial impact on functionality, which is one of the major differences with segmental resection for colon cancer. As a rectal carcinoma is located more deeply in the pelvis, decreased visibility, locoregional ingrowth in other organs and a narrow operation field complexes the surgical procedure. Recently, a modification of the traditional TME has been introduced. This, so called TaTME (transanal total mesorectal excision) combines the abdominal approach with a transanal approach during the dissection of the mesorectum. Despite the fact that the long term oncologic outcomes of the procedure are still to be awaited, this procedure is rapidly gaining popularity because of the increased visibility down in the pelvis and relatively easier mobilisation of the rectum during thebetter construction of the anastomosis, related to a single stapling technique. 9 Anastomotic leak The technical armamentarium of the surgeon is still expanding and so are the varieties in complications that can occur. To a much greater extent than in colonic surgery, the decision to restore continuity (to construct an anastomosis and connecting the two bowels ends) in rectal surgery is based on multiple factors. Comorbidity of the patient, age, preoperative sphincter function, tumour distance from the anal verge, resection margin in relation to the sphincter complex and patients preference are all being taken into account in order to prevent the most dreaded complication following colorectal surgery, namely anastomotic leakage. The definition of an anastomotic leak has been debated through the years due to the wide variety of 8

11 clinical symptoms with which it is associated. In this thesis the definition is recommended as proposed by the International Study Group of Rectal cancer, which is A defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments. 10 The early diagnosis of an anastomotic leak is not only crucial to minimize the degree of its sequelae, but also increases the probability of preserving the anastomosis. 11,12 Clinical signs of anastomotic leaks include fever, ileus, abdominal pain, abdominal distention and even pulmonary and cardiac symptoms. 10 All these symptoms can be absent or might be vague, especially if a diverting ileostomy is present. This has prompted towards the use of more objective parameters, of which CRP measurement has been shown to be a reliable predictor of postoperative infectious complications. Clinical evaluation and imaging can be misleading when not conducted complementarily. Therefore adequate timing of imaging is of great importance. A contrast study performed too early increases the false negative rate of the test. 13 However delayed diagnosis of the leak is associated with poorer outcomes on the long term. Using a cut-off level for day 3 or 4 CRP measurement can help in selective radiological evaluation of the anastomosis, with optimisation of its diagnostic performance. In the acute phase of a symptomatic anastomotic leak, the primary goal of the treatment is control the sepsis. Traditionally when continuity is not intended, the leaking anastomosis is dismantled and an end-colostomy is constructed. If continuity is preferred on the long term, the anastomotic leak should be diverted if not done so primarily and subsequently, drainage of the sepsis is the cornerstone of the treatment. TME surgery creates a large cavity behind the anastomosis where pus and debris can accumulate in case of a leak. The anal sphincter thereby functions as a physiologic barrier preventing drainage via the anus. Drainage of the sepsis can be performed using a transabdominal, transgluteal or transanal drainage. With this type of drainage, the healing rate of the anastomosis is around 50%. 11 However, this could take months before the leak has closed. So, the patient must be prepared for an intensive treatment period. 12 Therefore new strategies are being investigated. 11 In 2008, Weidenhagen introduced a negative pressure device that enables a more active drainage of the presacral abscess. 14 This, so called Endosponge is placed endoscopically into the abscess cavity. By exchanging it twice a week and tapering the 9

12 General Introduction size of the Endo-sponge sequentially, the cavity gradually collapses. Endosponge treatment in this early phase shows a healing rate of 75%. 14 This technique is labourintensive, expensive and it could take several weeks or even months before healing of the anastomosis is achieved. Therefore t modifications of this technique are currently being investigated in which the Endosponge therapy is combined with an early transanal closure of the anastomotic defect. With the results of larger studies on these techniques being awaited, it at least enables the surgeon a more step-up approach of the anastomotic leak, thereby leaving resection of the anastomosis and the construction of an end-colostomy as a last resort option. Snapshot studies The term Snapshot is relatively new in surgical research and was introduced in the United Kingdom. The so-called multicentre, snapshot cohort study enables the collection of outcomes from a large group of patients in a short period of time. 15 It is a form of collaborative research, in which young doctors of different hospitals are asked to participate in the data-acquisition. As participation results in an authorship, it is an easy, time effective manner for young doctors to get in touch with doing research and to expand their scientific circle. But more importantly, this collaborative study design enables a cross-sectional overview of a specific study-population in a predefined moment in time (Snapshot). A snapshot cohort study makes it possible to correlate the outcomes of provided healthcare with the type of treatment the patient received, without using strict inand exclusion criteria and with all variation in practice incorporated. Because large numbers of patients can be collected, there is enough statistical power to zoom in on specific patient groups. Although such data cannot be seen as conclusive evidence, this might generate interesting hypotheses, that subsequently can be explored by more traditional study designs. In addition to the short-term results of a national colorectal cancer audit 6, the snapshot design can be used to expand these data with long-term outcomes during an almost similar follow-up period for included patients, which is an advantage to the inherent problems of a wide range in follow-up if using a longitudinal study design. This application of the snapshot design has the potential to get insight on the quality of daily clinical practice on a nationwide basis beyond the often reported postoperative outcomes. 10

13 References 1. Jullumstro E, Wibe A, Lydersen S, Edna TH. Colon cancer incidence, presentation, treatment and outcomes over 25 years. Colorectal Dis 2011;13: Cheynel N, Cortet M, Lepage C, Benoit L, Faivre J, Bouvier AM. Trends in frequency and management of obstructing colorectal cancers in a well-defined population. Diseases of the colon and rectum 2007;50: Bonjer HJ, Deijen CL, Haglind E, Group CIS. A Randomized Trial of Laparoscopic versus Open Surgery for Rectal Cancer. The New England journal of medicine 2015;373: Vlug MS, Wind J, Hollmann MW, et al. Laparoscopy in combination with fast track multimodal management is the best perioperative strategy in patients undergoing colonic surgery: a randomized clinical trial (LAFA-study). Ann Surg 2011;254: Bruns ER, van den Heuvel B, Buskens CJ, et al. The effects of physical prehabilitation in elderly patients undergoing colorectal surgery: a systematic review. Colorectal Dis 2016;18:O Van Leersum NJ, Snijders HS, Henneman D, et al. The Dutch surgical colorectal audit. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2013;39: Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986;1: Clancy C, Burke JP, Albert MR, O Connell PR, Winter DC. Transanal endoscopic microsurgery versus standard transanal excision for the removal of rectal neoplasms: a systematic review and meta-analysis. Diseases of the colon and rectum 2015;58: Penna M, Hompes R, Arnold S, et al. Transanal Total Mesorectal Excision: International Registry Results of the First 720 Cases. Ann Surg Rahbari NN, Weitz J, Hohenberger W, et al. Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery 2010;147: Gardenbroek TJ, Musters GD, Buskens CJ, et al. Early reconstruction of the leaking ileal pouch-anal anastomosis: a novel solution to an old problem. Colorectal Dis 2015;17: van Koperen PJ, van der Zaag ES, Omloo JM, Slors JF, Bemelman WA. The persisting presacral sinus after anastomotic leakage following anterior resection or restorative proctocolectomy. Colorectal Dis 2011;13: Doeksen A, Tanis PJ, Wust AF, Vrouenraets BC, van Lanschot JJ, van Tets WF. Radiological evaluation of colorectal anastomoses. International journal of colorectal disease 2008;23: Weidenhagen R, Gruetzner KU, Wiecken T, Spelsberg F, Jauch KW. Endoluminal vacuum therapy for the treatment of anastomotic leakage after anterior rectal resection. Rozhl Chir 2008;87: Bhangu A, Kolias AG, Pinkney T, Hall NJ, Fitzgerald JE. Surgical research collaboratives in the UK. Lancet 2013;382:

14 General Introduction Outline of the thesis This thesis is divided into three parts. Part I focusses on the preoperative optimisation of colorectal cancer patients, thereby emphasizing on the treatment of preoperative anaemia with iron therapy in the work-up towards surgery. In Part II, rectal preserving strategies for early rectal cancers are being investigated. The third and last part of this thesis focusses on the long term surgical complications following rectal surgery. With the use of a Snapshot-study design, a cross-sectional overview was created of the provided surgical care of 71 hospitals throughout the Netherlands. Moreover, a minimally invasive treatment option for early detected anastomotic leak is discussed as well as more complex surgical options for patients with a chronic presacral sinus. A chronic sinus is defined as a pelvic abscess that is present for more than a year after the initial operation. Part I - Preoperative optimisation of CRC patients: Concomitant anaemia is present in approximately one third of the patients undergoing surgery for a colorectal carcinoma. Preoperative anaemia is associated with increased postoperative morbidity and mortality. As opposed to blood transfusions or Recombinant Human Erythropoietin (EPO), iron therapy as treatment of anaemia is known to have less side effects and is cheaper. In Chapter 1 the results are presented of the available literature on the efficacy of preoperative iron therapy in the treatment of preoperative anaemia. As a next step folloing this literature search, a multicentre randomised trial protocol is presented in Chapter 2, in which the efficacy of intravenous iron supplementation versus oral iron supplementation in the treatment of preoperative anaemia and its effects on postoperative complications and blood transfusion rates is investigated. Part II - Minimally invasive treatment strategies for early rectal cancer In Chapter 3, we present the results of a systematic literature review on the oncologic outcomes of patients with early staged (pt1-2) rectal carcinomas who were treated with completion surgery or adjuvant (chemo)radiotherapy following local excision, thereby preserving the rectum. The found paucity in available evidence on this specific topic led to the design of a randomised controlled trial, of which the trial protocol is described in Chapter 4. In this multicentre trial, patients with an inter- 12

15 mediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomised between adjuvant chemo-radiotherapy limited to the mesorectum and standard completion total mesorectal excision (TME). Primary endpoint is local recurrence after three-years of follow up. Chapter 5 describes the natural disease course in terms of local recurrence and survival for patients that were solely treated with a local excision (TEM) for a more advanced early rectal cancer. In the described cases, it was decided to deviate from the national guideline that recommends completion TME-surgery, as patient s condition or preference would not allow for any further therapy. In Chapter 6 a synopsis is described of all available national and international guidelines on rectal preserving treatment options, in order to determine current consensus and controversy among treatment recommendations for early rectal cancer. Part III - Complications following rectal surgery Chapter 7 encompasses a book chapter that was published in an educational book on gastrointestinal surgery that offers a stepwise description and treatment of complications that can occur following surgery of the rectum. A cross-sectional overview of long-term outcomes of patients who underwent rectal cancer resection in 2011 was generated by retrospectively analysing the patient files in 2015 by a group of more than 180 collaborators in a Snapshot study design. In Chapter 8, a general overview of this cohort is presented and placed into perspective, by benchmarking with the original datasets of two landmark randomised controlled trials on rectal cancer in. As anastomotic leakage is the most dreaded complication following rectal cancer surgery, we described its incidence, predisposing factors and long term outcomes based on this Snapshot cohort in Chapter 9. A third analysis within this project was related to inter-hospital variability exists in restoring continuity after low anterior resection for rectal cancer as well as in the construction of a diverting stoma. Chapter 10 aimed to determine long term outcome of two different approaches to the construction of a diverting stoma after low anterior resection at hospital level. In Chapter 11 the efficacy of early transanal closure of the anastomotic defect after pre-treatment with Endosponge therapy is being investigated as a new and minimally invasive approach of anastomotic leakage. In case the anastomotic leak persists after initial treatment and bowel continuity is desired, a redo-operation with 13

16 General Introduction resection of the leaking anastomosis and the construction of a new anastomosis is the patients only chance to avoid a permanent stoma. In Chapter 12 the feasibility of transanal minimally invasive surgery (TAMIS) as approach in redo anastomotic surgery is being evaluated, as well as other indications for pelvic redo surgery using TAMIS. If a chronic sinus remains with severe clinical problems (pain, severe purulent discharge, bleeding, secondary fistula, fasciitis) and bowel continuity is not an option. Salvage surgery shoud consist of completion proctectomy with complete debridement of the sinus (and fistula tracts) followed by an omentoplasty to fill the presacral cavity. This surgical technique is being evaluated in Chapter