----------------------- Page 1----------------------Review Patient optimization for gastrointestinal cancer surgery 1 2 K. C. Fearon , J. T. Jenkins , F. Carli 3 and K. Lassen 4

1Clinical Surgery, University of Edinburgh, Royal In rmary of Edinburgh, Edinburgh , and 2 Department of Colorectal Surgery, St Marks Hospital, Northwick Park, Harrow, UK, 3Department of Anaesthesia, McGill University Health Centre, Montreal, Quebec, Canada, and 4 Department of Gastrointestinal and Hepatopancreatobiliary Surgery, University Hospital of Nort hern Norway and Institute of Clinical Medicine, University of Troms, Troms, Norway Correspondence to: Mr K. Lassen, Department of Gastrointestinal and Hepatopancre atobiliary Surgery, University Hospital of Northern Norway, 9038 Troms, Norway (e-mail: lassen@unn.no) Background: Although surgical resection remains the cen element in curative treatment of gastrointestinal cancer, increasing emphasis and resource has been focuse d on neoadjuvant or adjuvant therapy. Developments in these modalities have improved outcomes, but far less attention has been paid to improving oncological outcomes through optimization of perioperative c are. Methods: A narrative review is presented based on available and updated l iterature in English and the authors experience with enhanced recovery research. Results: A range of perioperative factors (such as lifest yle, co-morbidity, anaemia, sarcopenia, medications, regional analgesia and minimal access surgery) are m odi able, and can be optimized to reduce short- and long-term morbidity and mortality, improve functiona l capacity and quality of life, and possibly improve oncological outcome. The effect on cancer-free and o verall survival may be of equal magnitude to that achieved by many adjuvant oncological regimens. Modulat ion of core factors, such as nutritional status, systemic in ammation, and surgical and disease-mediated stress, probably in uences the hosts immune surveillance and defence status both directly an d through reduced postoperative morbidity. Conclusion: A wider view on long-term effects of expanded or targeted enh anced recovery protocols is warranted. tral Paper accepted 25 September 2012 Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bj s.8988 Introduction rtunity to achieve the best oncological outcome may ompromised. oppo be c

Resection of the primary tumour remains the principal M ost patients with cancer are managed by element of treatment and potential cure for the majority multiprof essional and multidisciplinary teams (MDTs) involving of solid epithelial malignancies. However, surgery itself surg eons, pathologists, radiologists, medical and clinical is only one component of a complex series of assessonco logists, cancer nurse specialists and audit support. ments and interventions that make up the patients cancer journey. Beyond a histological diagnosis and radiological ite this, treatment plans will sometimes be agreed staging, patients may undergo neoadjuvant chemotherapy, re a patient is assessed fully and discussions do not resection of the primary lesion, adjuvant chemotherapy, ys consider the patients speci c co-morbidities, nutrisurgical metastasectomy, palliative chemotherapy, palliaal status or cardiopulmonary reserve. A pragmatic view tive surgery and then be entered into phase I drug trials. t be that the cancer treatment is necessary and that, Not all will pass down this complex route, particularly nd gross impairment, patients will survive. On the those with early-stage disease for whom surgical cure is r hand, variation in outcomes suggests that variables readily achieved. For those with signi cant co-morbidity e routine MDT decision-making may be imporor advanced disease, the complexities and toxicities of their and worthy of consideration. For example, there are treatments mean that at various critical time points, witheon and institution league tables that show considout due attention to optimizing overall physiology, the le variation in 30-day morbidity and mortality for 2012 British Journal of Surgery Society Ltd British Journal of Surgery 2013; 100: 1527 Published by John Wiley & Sons Ltd ----------------------- Page 2----------------------16 K. C. Fearon, J. T. Jenkins, F. Carli and K. Lassen 1 he need for palliative surgical intervention. As such, standard cancer surgery , and international comparisons of long-term cancer outcomes show considerable variaminated cancer constitutes a risk factor for morbidity tion between countries2 . The main discussion at a MDT ortality following surgery8. meeting may focus on the small but signi cant bene t of tumours, even when still at a curable stage, adjuvant or neoadjuvant chemotherapy or radiotherapy. cause physiological derangements and malnutrition, However, it is relevant to consider that effects of the same asing risk of complications and death. Usually, these magnitude on long-term cancer recurrence and survival and t disse and m Some may incre are Desp befo alwa tion migh beyo othe outsid tant surg erab

tumours obstructing the upper gastrointestinal (GI) may result from postoperative morbidity, for example an iliary tracts. Conversely, the effects of obstruction anastomotic leak3,4 or a complication that delays signi al tissues that in uence healing and the risk of cantly the start of adjuvant chemotherapy5. Equally, being omotic leak can be quite different. Grossly dilated elderly and undergoing an oesophagectomy is associated bowel caused by a obstructing tumour is a risk factor with reduced use of adjuvant therapy, increased 30-day nastomotic leak9, whereas an obstructed and dilated mortality, reduced overall 5-year survival and reduced 5in an atrophic and chronically in amed pancreatic year cancer-free survival6. It is against this background that is favourable in terms of risk of stula formation or the issue of patient optimization for cancer surgery needs omotic breakdown10. to be considered. The likelihood of metastatic spread depends on the

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Neoad juvant treatments balance between the metastatic potential of the tumour and host defences, of which cell-mediated immunity and ome GI cancers, at a locoregional level, neoadjuvant natural killer cell function are particularly in uential. erapy (and/or radiotherapy) affects outcome by These components provide immune surveillance, and ing tumour size, improving ease of resection and are in uenced by factors including nutritional status kelihood of positive margins. Still, preoperative and systemic in ammation. This has led to a focus on ical therapy per se , or the choice of agent modi able perioperative factors that may tip the balance iation doses, may increase short-term morbidity in favour of reduced cancer spread and recurrence. ven mortality and in generating morbidity may Over the past 10 years there has been a revolution in sely alter long-term outcome. These risks must be the nature of perioperative care with the introduction dered carefully for each patient. Apart from the of enhanced recovery after surgery (ERAS) protocols. quences following bone marrow depression or gut These place particular emphasis on diminishing the stress al sloughing, some organ-speci c side-effects are response while maintaining homeostasis. Although it is described. Rectal resections are associated with a 7 clear that ERAS is safe and reduces complications , r risk of short-term morbidity following preoperative there has been no systematic review that identi es on therapy11, and oesophageal radiation induces speci c elements of an ERAS pathway that positively and tissue healing problems12, as well as being toxic independently in uence long-term cancer outcomes. heart and lungs13. Preoperative chemotherapy for Short-term issues such as 30-day morbidity and ectal liver metastasis, mainly with irinotecan and In s chemoth reduc the li oncolog or rad or e adver consi conse mucos well highe radiati local to the color

mortality and the longer-term cancer-speci c outcomes atin, may cause damage to the liver parenchyma, (local and systemic recurrence, disease-free survival) are asing both complication rates and critical volume for important to both clinicians and patients. The purpose of future liver remnant14. Neoadjuvant chemotherapy this review is to explore how these two domains interact oesophageal cancer is associated with signi cant during the perioperative period, to determine when the of skeletal muscle mass15, a reduction in quality surgeon and anaesthetist should in uence one to improve e and impaired physical activity levels16. Trials the other, and suggest methods whereby this might be ating perioperative chemotherapy for resectable achieved. ic adenocarcinomas have not identi ed an increase stoperative complications17. Assessing the impact of disease and treatment The disease cal treatment The spectrum of clinical presentation of malignant disease nature and extent of surgery is often determined can range from small tumours that produce neither he perceived stage of disease and frequently follows symptoms nor physiological dysfunction to disseminated andardized approach. However, it is important to disease precipitating anaemia, malnutrition and cachexia nize situations in which modi cations are needed 2012 British Journal of Surgery Society Ltd .co.uk British Journal of Surgery 2013; 100: 1527 Published by John Wiley & Sons Ltd ----------------------- Page 3----------------------Patient optimization for gastrointestinal cancer surgery 17 owing to deranged physiology that cannot be corrected the context of traditional perioperative care, reduced promptly or because of unexpectedly severe side-effects body protein mass (mainly skeletal muscle) has been following preoperative oncological treatments. Based on d to adverse surgical outcome38. In an ERAS setting, large databases, various case-mix or prognostic tools the stress of surgery is minimized, low body mass rank abdominal operations according to the magnitude (BMI) does not appear to be an independent risk of surgical trauma and hence complication risks1820. for complications or prolonged length of stay, For abdominal cancer surgery, the risks are highest sting that baseline nutritional status may not be as in oesophageal resection, major pancreatic and hepatic cal in this setting as in more traditional perioperative

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Tools have been developed to take into account the that the average BMI of patients is often in the factors above and the state of the patients resilience to ght or obese range and this may hide underlying trauma (see below). These tools, such as the Portsmouth e wasting. A recent study has demonstrated that the modi cation of the Physiological and Operative Severity e of low muscle mass is predictive of complications Score for the enUmeration of Mortality and morbidity ength of stay following colorectal surgery40 . Whether (P-POSSUM) and the modi ed form of Estimation of uscle wasting relates to pre-existing co-morbidity Physiologic Ability and Surgical Stress (mE-PASS)19,20, ncer-associated muscle loss is not known. Obesity is attempt to encompass the disease, the planned oncological present in patients with cancer, and the associated and surgical treatment, as well as patient factors. Although olic syndrome with insulin resistance leads to a validated repeatedly against large outcome registries, such ellation of pathological changes that in turn can tools have yet to gain wide adoption for individuals. They r recovery. are useful as case-mix calculators to allow comparison lmonary dysfunction such as chronic obstructive pulbetween larger groups treated differently or by different y disease has been associated with postoperative pulcentres, to ensure comparable baseline risk. y complications in oesophageal cancer resection41 . arly, cardiac diseases and abnormalities of cardiac Assessing the patient m can in uence the course of postoperative events42 . ty and depression are common features in patients General cancer, and result in poorer postoperative healing and 43 Socioeconomic ery . status, health literacy and ethnicity are

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associated with signi cant disparities in cancer-related outcome21,22, and age is probably an independent risk ization factor23 . Daily smokers and abusers of alcohol have an increased risk of postoperative complications24,25, nt information and counselling and in both situations outcome has been improved 2629 core items of the . Obesity is linked 30,31

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perative pathway may reduce discomfort and anxiety to ethnicity and socioeconomic status , but its role as 44,45 and i mprove recovery , and is generally recommended an independent risk factor for surgical morbidity is not 46,47 clear3236. Obesity is associated with increased conversion protocols . rate, operating time and postoperative morbidity in some laparoscopic colorectal surgery series, but does not affect uctive jaundice surgical safety or oncological margins37. ice is associated with immunosuppression and gut mucos al dysfunction. A high bilirubin level in combination Co-morbidity low albumin and raised creatinine concentrations is Ageing is characterized by changes in pulmonary gly predictive of adverse outcome following major bilcardiovascular systems, metabolic disorders and reduced tract surgery48 . Although researched extensively4953 , and with stron iary the e been The m that 250 mo drain www.bjs

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muscle mass. Co-morbidities associated with ageing ffects of preoperative biliary drainage on outcome have include hypertension, hypercholesterolaemia, chronic inconsistent, suggesting neither harm nor bene t. obstructive airway disease and diabetes. Age per se is not ost recent of the large randomized trials concluded an exclusion criterion for cancer surgery. The presence of patients with serum bilirubin concentrations below coexisting diseases has a greater impact on postoperative l/l should not undergo routine preoperative biliary morbidity and mortality than age alone. age54. 2012 British Journal of Surgery Society Ltd .co.uk British Journal of Surgery 2013; 100: 1527 Published by John Wiley & Sons Ltd ----------------------- Page 4----------------------18 K. C. Fearon, J. T. Jenkins, F. Carli and K. Lassen Anaemia used routinely for perioperative treatment of patients 55 rgoing non-cardiac surgery unless they are being Anaemia is generally considered a risk factor for surgery n for clinically indicated reasons, such as heart failure, associated with more advanced disease stage, nary artery disease or previous myocardial infarction mortality and morbidity rates, and longer hospital stay higher 74 56 . . ,

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S tatin use has been associated with a decreased mortality Although extensive blood loss during surgery 75 after non-cardiac surgery replaced, transfusion of must be rate , probably owing to antiallogeneic red blood cells is in amm atory and plaque-stabilizing effects. associated with earlier cancer recurrence and poorer 5760 irin therapy for the purposes of primary and seclong-term survival . Establishing a causal relationship 61 ry prevention of cardiovascular disease should be is impossible from observational studies alone , as inued during the perioperative period in all patients intraoperative dif culties and postoperative complications with coronary artery, cerebrovascular or peripheral vascuare confounders. The concept of an immunosuppressive disease76. effect (such as a reduction in T helper cell and natural ssessment of pulmonary function is a valid indicator of killer cell count, and a reduction in cytokine production post operative pulmonary complications. A forced expiraincluding interferon ) from blood transfusion affecting 61 volume in 1 s of less than 70 per cent of predicted the hosts immunological surveillance is well accepted e requires assessment and treatment. Preoperative Interestingly, transfusions may have a greater adverse effect resp iratory muscle training in patients undergoing thowhen given after surgery than when given during the 58,61 c surgery has been shown to prevent postoperative operation , and neither autologous transfusion (selfonary complications by increasing inspiratory and donation) nor leucocyte reduction of transfused blood 77 62,63 ratory muscle strength . changes recurrence rates or survival . The consequence of preoperative correction of malignant or iron-de ciency anaemia is uncertain. For patients failure with colorectal cancer, preoperative oral iron therapy has nic kidney disease, even in relatively early stages, been submitted to randomized study, reducing transfuassociated with an increased rate of postoperative sion requirements and increasing haemoglobin and ferritin ction78,79. Patients should be kept adequately hydrated, levels64 . More evidence is needed to establish a role for raci pulm . valu tory lar A Asp onda cont

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further hazards to renal function (such as antibiotics intravenous iron therapy and/or erythropoietin in the prenalgesics) assessed and modi ed78. 65,66 operative and perioperative setting . hosis and liver failure Cardiovascular and respiratory insuf ciency

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Cirr The liver hosts the largest resident macrophage population Cardiac complications are a major source of intraoperffer cells) in the body and liver failure is associated ative and postoperative morbidity and mortality67. The systemic immunosuppression. Cirrhosis in nonliterature on cardiac adverse events has evolved from pretic surgery is associated with increased complications diction to optimization through intervention. Careful risk mortality80. This risk increases signi cantly in strati cation is fundamental67,68. In general, risk factors major surgery and emergency surgery, and in include age, congestive cardiac failure, BMI greater than presence of portal hypertension80. Morbidity and 30 kg/m2, cardiovascular disease, hypertension, emergency ality rates correlate with the degree of cirrhosis as surgery, duration of surgery and units of blood transfused. ured by standard models, including the preoperative More speci c clinical risk indices exist that have high capafor End-stage Liver Disease (MELD) and bility for discriminating patients at risk of major cardiac dTurcottePugh (CTP) grade80. On the other hand, events69 and assist in decision-making with preoperative majority of minor and intermediate procedures can be optimization. rtaken relatively safely in patients with low MELD Pre-emptive beta-blockade has received much attene or CTP grade A80. The overall bene t of preoperative tion70. Although repeatedly shown to reduce the risk of sjugular intrahepatic portosystemic shunt in patients perioperative cardiac complications70, the risk of serious portal hypertension remains unclear80. stroke was increased signi cantly in some trials71,72. Well regulated preoperative beta-blockade has been advocated to be safer than perioperative initiation73. Careful selection etes and dosage is crucial to achieve a net reduction in existing diabetes mellitus confers an increased risk postoperative complications68. Beta-blockers should not postoperative morbidity and mortality in colorectal 2012 British Journal of Surgery Society Ltd s.co.uk British Journal of Surgery 2013; 100: 1527 Published by John Wiley & Sons Ltd ----------------------- Page 5----------------------(Kup with hepa and both the mort meas Model Chil the unde scor tran with

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Patient optimization for gastrointestinal cancer surgery 19 surgery81,82. Although anastomotic leak rates however, support a mortality bene t from oral antiare not not, coag

increased, mortality rates after a leak are substantially ulation in patients with cancer. There is an increased 81 89 increased in diabetics . There appears to be an association of bleeding . between morbidity and preoperative hyperglycaemia81, indicating that these patients require careful assessment.

risk

Nonsteroidal anti-in ammatory drugs The effect of rigid glycaemic control before surgery is, 81,82 tanoids have long been recognized as potential tumour however, less clear . crine growth factors. There is increasing epidemiologi cal evidence that aspirin can reduce cancer prevalence and recurrence90 . There is evidence from animal models Malnutrition and cachexia/sarcopenia that a single perioperative dose of the cyclo-oxygenase 2 Poor nutritional status is associated with worse outcome bitor celecoxib can inhibit chronic morphine-induced after major surgery. Traditionally, patients with gross canotion of angiogenesis, tumour growth, metastasis and cer cachexia requiring surgery have received 1014 days of ity91 . The in uence of perioperative use of nonpreoperative parenteral or enteral nutrition83. It is relevant oidal anti-in ammatory drugs on long-term outcomes to consider that patients with gross cachexia may have more atients with cancer is not known. advanced disease than previously assumed and should be restaged carefully as heroic attempts at resection of their primary disease may be unsuccessful. A more conservative oving functional reserve approach (such as luminal stenting) may provide a better overall outcome. ical prehabilitation opulations of patients with cancer with pre-existing Medications ntia, low preoperative albumin level, poor exertolerance and frailty remain especially vulnerable to Morphine operative complications. Cognitive impairment delays Recent epidemiological studies have examined the impact rn to baseline performance. A decline in physical activinhi prom mortal ster of p Pros auto

Impr Phys Subp deme cise post retu

of perioperative anaesthetic or analgesic agents on longas a result of ageing and cancer represents a signi cant term survival after surgery for various types of maligthat can be attenuated by physical exercise as a prevennancy including rectal84 and prostate85 cancer. Some intervention. Poor preoperative tness scores are assostudies suggest a reduced recurrence with regional ed with increased mortality, longer postoperative hospianaesthesia/reduced use of opioids84,85, whereas others stay and increased complications92,93 . Most physiotherdo not86. Potential mechanisms include reduced stress and dietary interventions aimed to promote recovery responseimmunosuppression with regional anaesthesia or rried out after surgery (rehabilitation) when patients a direct effect of opioids on tumour growth and metastasis. fatigued and emotionally vulnerable, and thus unable to The effect of morphine on tumour growth is controverly with intense recovery programmes. It seems plausial, with both growth-promoting and growth-inhibiting e that optimal physical functioning before surgery (preeffects being observed. Evidence suggests that morphine litation) might result in better postoperative outcome. can affect proliferation and migration of tumour cells as erobic and muscular strength training in elderly well as angiogenesis. Various signalling pathways are implients has been shown to increase endurance capaccated, including co-activation of the epidermal growth reduce weight gain, and improve muscle strength and 87 factor receptor by the -opioid receptor and overexpresof motion in a number of joints94 . Although consion of the -opioid receptor in lung cancer promoting Akt ts to proceeding with surgery limit the time for and mTOR activation, tumour growth and metastasis88. iation of preoperative physical activity, 3 weeks may be The potential for suppression of the immune system by ent to obtain a moderate gain in aerobic and muscle morphine is an additional issue. ngth reserve. Studies on prehabilitation before thoracic GI cancer surgery showed an increase in postoperaAnticoagulants functional exercise capacity, decreased postoperative A number of basic science and clinical studies have suglications and shorter hospital stay95,96 . It appears gested that oral anticoagulants may improve the survival of patients who are deconditioned require only moderpatients with cancer through an antitumour effect in addiphysical training to obtain an increase in functional tion to their antithrombotic effect. Existing evidence does city97,98 . The addition of nutritional supplements to 2012 British Journal of Surgery Society Ltd s.co.uk British Journal of Surgery 2013; 100: 1527 Published by John Wiley & Sons Ltd

ity risk tive ciat tal apy are ca are comp sibl habi A pati ity, range strain init suf ci stre and tive comp that ate capa www.bj

----------------------- Page 6----------------------20 K. C. Fearon, J. T. Jenkins, F. Carli and K. Lassen physical training has been shown to enhance further phys110. Results are not uniform111,112, however, and furiological reserve and impacts positively on postoperative data are needed, especially in diabetic patients113,114. functional exercise capacity99 . Whether such preoperative regimens produce long-term bene ts is untested. However, in the post-treatment phase, ing the immunological effects of cancer and an increase in physical activity has been associated with ery improved disease-speci c and overall survival, regardless of prediagnosis activity levels100102. al postoperative immune function increases risks postoperative infection and metastasis of tumour cell s115,116. Therefore, maintaining normal immune funcNutritional therapy tion , particularly cell-mediated immunity, in the periFor adequately nourished patients submitted to routine ative period may affect long-term oncological results. surgery within an ERAS programme there should be no ared with traditional open surgery, laparoscopic requirement for arti cial nutritional support as return of GI ions have been shown to decrease the stress response, function is a key priority, and the patient should be able to esult in lower levels of interleukin (IL) 6 and C-reactive eat and drink within 24 h of (non-oesophageal) surgery with ein, and to be associated with better preservation of a low risk of prolonged gut dysfunction. It has been shown ne competence as measured by human leucocyte antithat combining preoperative oral carbohydrate treatment, expression on monocytes117. Whether minimizing the epidural analgesia and early enteral nutrition balances ct on cell-mediated immunity produces true oncologinitrogen equilibrium with almost complete abrogation of advantage has yet to be proven, although extrapolations the metabolic response to injury103. For patients who are at been made from studies in which a survival advansigni cant risk of malnutrition (for example those underas identi ed in stage III colorectal cancer treated in going oesophagectomy), the use of cancer-speci c enteral paroscopic arm118. No other randomized trials have feeds may be justi ed to maintain lean body mass104. d a similar survival advantage with laparoscopy critics have raised concerns that a disparity in adjuvant ther oper Comp operat to r prot immu gen effe cal have tage w the la identi e and mass ther

Modify surg Abnorm of

apy use may have produced apparent advantage in the Immunotherapy/immunonutrition lapa roscopic arm. However, others suggest that the tranDifferent combinations of diets containing components on to adjuvant chemotherapy was facilitated by more aimed to enhance immune function in surgical patients pt recovery in the laparoscopic arm. There are no have been studied. These diets, often termed immunoonal data that provide a clear explanation. nutrition, usually contain combinations of arginine, gluis also relevant to consider the effect of postoperative tamine, omega-3 fatty acids and nucleotides. Several metaidity on immune function and outcome, and the analyses have been published on their clinical effectiveness. ntial systemic immunosuppressive effect of sepsis Most studies have shown clinical bene t by reducing mmation. Infectious complications are associated complications and shortening length of stay in the conan excessive and persisting synthesis and release text of traditional perioperative care, but the results are proin ammatory cytokines. Persisting high levels of heterogeneous105. There is evidence to suggest that such may decrease the number, maturation and activity treatment is most effective in malnourished patients, but cytotoxic T lymphocytes, natural killer and other there are no trials in an ERAS setting when stress is nocompetent circulating cells, such as dendritic minimized. gen-presenting cells. Low plasma levels of these cells high levels of IL-6 in the late postoperative period are corr elated with poor prognosis in colorectal cancer119,120. Carbohydrate loading t is clear that all efforts should be made to reduce To avoid patients undergoing surgery in an unfed state, idity to an absolute minimum, and a combination of complex carbohydrates can safely be administered orally ocol-driven perioperative care and minimally invasive 23 h before induction of anaesthesia. Carbohydrate treaty may permit this. Further studies are needed to ment like this has been shown to attenuate protein and rmine the relative contributions of both minor (such nitrogen loss, and decrease postoperative insulin resistance. ound infection) and major (for example reoperation, It reduces the sense of hunger, thirst and anxiety106108. motic leak and unplanned admission to the intensive Gut function immediately after colorectal surgery may be unit) morbidities on cancer-speci c, disease-free and improved109, as well as preservation of skeletal muscle all survival. 2012 British Journal of Surgery Society Ltd s.co.uk British Journal of Surgery 2013; 100: 1527 Published by John Wiley & Sons Ltd I morb prot surger dete as w anasto care over www.bj siti prom additi It morb pote and in a with of IL-6 of immu anti and

----------------------- Page 7----------------------Patient optimization for gastrointestinal cancer surgery 21 Attenuating the challenge to the patient ced recovery pathways Surgical access protocols designate a multimodal and evidencebased protocol-driven approach to perioperative care Laparoscopy attenuates the stress response, causes less aims to attenuate the surgical stress response and tissue damage and fewer adhesions, reduces pain and nsequence reduce rates of complications, enhance produces a shorter time to functional recovery, compared ery and reduce length of stay. As a by-product, cost with open surgery. The role of laparoscopy has been gs from successful protocols are substantial. A number scrutinized most closely in colorectal cancer surgery, uch protocols have been published46,47,121,127137, although its application for other GI malignancies is ng in comprehensiveness, numbers of elements evolving. yed routinely and the degree of validation138. The safety and advantages of laparoscopic colectomy for recently, the surgical community largely ignored cancer have been much debated and several randomized evidence, although ERAS protocols are being used clinical trials have clari ed these issues. When performed ingly. by surgeons with adequate experience and training, it e bene ts of introducing ERAS programmes have is clear that laparoscopic colorectal surgery dramatically demonstrated consistently, particularly in colorectal improves functional outcome following bowel resection. ry7,138140, but the impact on outcomes other than However, open abdominal surgery with modern enhanced to recovery has been modest. It should be noted than recovery protocols46,47,121 has also produced remarkable ring direct improvements after successful protocol reductions in time to functional recovery and length mentation is notoriously dif cult. For observational of stay121,122. Nevertheless, there is still a signi cant series, bias is introduced from the Hawthorne effect difference between open and laparoscopic surgery, and ents in trials do better)141,142. For experimentation, this is evident in both observational series and more recent a truly pure control group, which has received randomized trials. Failure to identify differences within art of an enhanced recovery protocol as standard ERAS care between open and laparoscopic colorectal is practically impossible. It is likely that, if such resection in earlier comparative studies is likely to relate up existed, ethical concerns would preclude their to the steep learning curve associated with laparoscopic sion in an experimental design. The true effect of that in co recov savin of s varyi emplo Until this increas Th been surge time measu imple cohort (pati nding no p care, a gro inclu Enhan ERAS

resection and a broad variation in what has been regarded comprehensive protocols must be shown as bene ts as laparoscopic123125. nd every protocol item (where feasible) or from The recent LAparoscopy and/or FAst track multimodal , multi-institutional and consecutive registries where management versus standard care (LAFA) trial included iance and outcome are carefully recorded. 400 patients from nine hospitals126. The study randomized though conventional ERASlaparoscopic pathways patients between laparoscopic or open surgery, and also focused on optimizing short-term recovery, it is now between ERAS and standard care. It demonstrated that that current elements of ERAS may need to be laparoscopy was the only predictive factor with an effect on and expanded to take account of the growing hospital stay and morbidity. Within the non-ERAS group ature that identi es the many factors that may in uence six of the prede ned 15 ERAS elements were applied rm oncological outcomes. The challenge will be to routinely, as it was felt unethical to leave these out. n and conduct trials with suf cient sample size to The role of laparoscopy in the management of rectal the value of each intervention. cancer has been assessed in the COlorectal cancer Laparoscopic or Open Resection (CoLOR) II trial, with 2 : 1 randomization to laparoscopy or open surgery143. osure Although operating times were longer, blood loss, hospital uthors declare no con ict of interest. stay and time to rst bowel movement were signi cantly improved in the laparoscopic group, with no difference in the anastomotic leak rate, overall morbidity or mortality. ences Similar studies are being conducted in the US (American van Gijn W, Gooiker GA, Wouters MW, Post PN, College of Surgeons Oncology Group (ACOSOG) Z6051) Tollenaar RA, van de Velde CJ. Volume and outcome in and in Japan (Japan Clinical Oncology Group (JCOG) 0404 colorectal cancer surgery. Eur J Surg Oncol 2010; trial). Trials that include thousands of patients are likely to 36(Suppl 1): S55S63. be required to determine the long-term oncological effects Baili P, Micheli A, De AR, Weir HK, Francisci S, of laparoscopyERAS. ntaquilani M et al.; CONCORD Working Group. Life 2012 British Journal of Surgery Society Ltd .co.uk British Journal of Surgery 2013; 100: 1527 Published by John Wiley & Sons Ltd ----------------------- Page 8----------------------22 K. C. Fearon, J. T. Jenkins, F. Carli and K. Lassen

these from each a large compl Al have evident modi ed liter long-te desig prove

Discl The a

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2 Sa www.bjs

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