ORIGINAL CONTRIBUTION
Do Anastomotic Leaks Impair Postoperative Health-related Quality of Life After Rectal Cancer Surgery? A Case-matched Study Annezo Marinatou, M.D. • George E. Theodoropoulos, M.D., Ph.D. Styliani Karanika, M.D. • Theodoros Karantanos, M.D. • Spiridon Siakavellas, M.D. Basileios G. Spyropoulos M.D., Ph.D. • Konstantinos Toutouzas, M.D., Ph.D. George Zografos, M.D., Ph.D. Colorectal Unit, First Department of Propaedeutic Surgery, Athens Medical School, Athens, Greece
BACKGROUND: Anastomotic leaks after colorectal resections for cancer are a leading cause of postoperative morbidity, mortality, and long hospital stay. Few data exist on the potentially deleterious effect of the anastomotic leaks after proctectomy for cancer on patient health-related quality of life.
36, Gastrointestinal Quality of Life Index, European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-C30, and European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-CR29).
OBJECTIVE: The aim of this study was to explore the
hospitalization. Although the numbers of initially constructed defunctioning loop ileostomies were not significantly different between cases and controls, “leak” patients were required to remain with a stoma significantly more often at all postoperative assessment time points. No differences were observed in the baseline scores between the 2 groups. Physical function of “leak” patients was significantly worse at all postoperative assessment time points. At 6 and 12 months, their emotional and social function and overall q uality-oflife scores were significantly decreased in comparison with the patients with an uncomplicated course. “Leak” patients experienced significantly more “stoma-related problems” and “sore skin” around the stoma site.
effect of clinically evident anastomotic leaks on h ealthrelated quality of life after rectal cancer excision. DESIGN: This is a case-matched study. SETTINGS: This study was conducted in a Greek academic surgical department. PATIENTS: Included were 25 patients undergoing low
anterior resection complicated by an anastomotic leak (Clavien classification II, n = 14, and III, n = 11) and 50 patients undergoing low anterior resection with an uncomplicated course. MAIN OUTCOME MEASURES: Health-related quality-of-life data were prospectively collected at fixed assessment time points (baseline, 3, 6, and 12 months postoperatively) by the use of validated questionnaires (Medical Outcomes Study Short Form Financial Disclosure: None reported. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Phoenix, AZ, April 27 to May 1, 2013. Correspondence: George E. Theodoropoulos, M.D., Ph.D., Athens Medical School, 7 Semitelou St, GR-11528 Athens, Greece. E-mail: [email protected] Dis Colon Rectum 2014; 57: 158–166 DOI: 10.1097/DCR.0000000000000040 © The ASCRS 2014
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RESULTS: “Leak” patients required a longer
LIMITATIONS: Limited number of patients, restriction of follow-up to the end of the first year, and heterogeneity in terms of the presentation, severity, and management of anastomotic leaks were the limitations of this study. CONCLUSIONS: Anastomotic leaks have an adverse effect on postoperative health-related quality of life.
KEY WORDS: Colorectal cancer; Anastomotic leak;
Health-related quality of life; Medical Outcomes Study Short Form 36; Gastrointestinal Quality of life Index; European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-C30. Diseases of the Colon & Rectum Volume 57: 2 (2014)
Diseases of the Colon & Rectum Volume 57: 2 (2014)
A
nastomotic dehiscence after colorectal resections is recognized as a leading cause of postoperative morbidity, mortality, and long hospital stay.1–4 Its prognostic relevance for adverse oncologic outcomes is included among its disastrous consequences.5–7 Long-term functional derangement after restorative rectal excisions complicated by anastomotic leaks has been reported in rather limited previous studies.8–11 Health-related quality of life (HRQoL) has been established as an important outcome measure of surgical treatment success and may be closely related and directly affected by functional disorders arising from a postoperative complication, such as an anastomotic failure.11 Postcolectomy complications have been associated with worse HRQoL in patients with colorectal cancer.12,13 Nevertheless, only 1 recently published series has eloquently addressed the potentially deleterious effect of the anastomotic leaks after proctectomy for cancer on patients’ long-term HRQoL.11 Health-related quality of life after colorectal resections for malignancy can usually be restored up to the end of the first postoperative year.14–17 Stressing factors such as the physical and emotional adaptation after the surgical and psychological trauma, the administration of adjuvant treatment with deleterious side effects, and the need to tolerate a reversible, potentially temporary stoma until anastomosis is well healed are usually all entirely accumulated during the time period of the first year following surgery. In the present study, our null hypothesis was that anastomotic leaks after low anterior resections for cancer do not affect HRQoL during the first postoperative year. Therefore, in an effort to show the impact of anastomotic leaks on common HRQoL domains, we conducted a case-matched study between patients who experienced a symptomatic anastomotic leak after rectal resection for cancer and patients with an uneventful recovery.
METHODS Patients and Data Collection
In this retrospective case-matched study, data were derived from a prospectively collected and maintained, institutional review board-approved, clinical and HRQoL database on patients who have biopsy-proven colorectal cancer and who were surgically managed between 2007 and 2012 at the First Department of Propaedeutic Surgery of Athens Medical School. Documentation of demographic, clinical, operative, postoperative, and pathologic characteristics was performed in detail. Twenty-five patients with clinically evident anastomotic leak after a restorative rectal cancer operation with therapeutic intent were selected. Four of them had been referred from other institutions after the occurrence of the leak, and 5 of them had been fully managed in a neighboring nonacademic department of the same hospital, but they were followed up in terms
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of HRQoL by our colorectal unit. The “leak” patients were age (±5 years), sex, and stage matched in a 1:2 fashion with 50 patients who had rectal cancer with an uncomplicated course, who were retrieved from a cohort of 350 patients who had undergone colorectal resection for neoplasms during the same time period. An independent reviewer, who was blinded to all clinical data except the matching criteria, matched the patients manually one by one on the basis of these variables. Patients’ features and clinical details are depicted in Table 1. Patients younger than 18 and older than 80 years, with distant metastatic disease at presentation, initially managed on an emergency basis and with a history of IBD or hereditary cancer were not included. The standard operative technique included total mesorectal excision in patients with tumors in the lower and mid rectum, and partial mesorectal excision with transection of the mesorectum at least 5 cm distal to the tumor in patients with cancer of the upper rectum. A defunctioning “protective” loop ileostomy was constructed as preferred by the surgeon in the majority of the cases where a low-lying anastomosis was necessary. In the 25 patients without complications, the cardinal clinical findings that led to suspicion and/or diagnosis of the anastomotic leak were the following: peritonitis (9 patients), purulent and/ or feculent material from the intraoperative placed pelvic drain (5 patients, all with initial diverting stoma), fever with or without “pelvic” pain (5 patients, 3 of them with initial diverting stoma), protracted ileus (3 patients, all with initial diverting stoma), drainage per rectum (2 patients, 1 with initial diverting stoma), and rectovaginal fistula (1 patient, with initial diverting stoma). Confirmation of the anastomotic insufficiency was obtained by CT and/or a contrast medium exploration (Gastrografin) in 18 patients. Fourteen anastomotic leaks were classified according to Clavien complication classification as grade II (not requiring interventional treatment), and 11 of them were classified as grade III (requiring surgical, endoscopic, or radiologic intervention).18 The management of anastomotic leak included primarily conservative measures consisting of the maintenance of the intraoperatively placed pelvic drain (3–6 weeks) (12 cases, all with initial loop ileostomy) and spontaneous transrectal drainage (2 cases, 1 with initial loop ileostomy), as well as CT-guided placement of a presacral drain (1 case); relaparotomy, lavage, and pelvic drain placement (2 cases); relaparotomy, lavage, and loop ileostomy (3 cases); and relaparotomy with takedown of anastomosis and end colostomy construction (5 cases). Although preoperative marking was the standard practice for all electively constructed ileostomies, an appropriate stoma marking did not precede the 8 emergently constructed stomas in the operative management of the leaks.
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TABLE 1. Characteristics and treatment-related factors of patients with and without anastomotic leak
Age Sex, male BMI ASA classification ASA I ASA II ASA III ASA IV Tumor stage I II III Tumor location Upper rectum Mid rectum Lower rectum Level of anastomosis, cm from anal verge Type of anastomosis Colorectal Coloanal Stapled Handsewn End-to-end Colonic J-pouch Transverse coloplasty Total days of hospitalization Protective loop ileostomy at initial operation Presence of stoma at discharge (loop ileostomy/end colostomy) Presence of stoma at 3 mo (loop ileostomy/end colostomy) Presence of stoma at 6 mo (loop ileostomy/end colostomy) Presence of stoma at 12 mo (loop ileostomy/end colostomy) Adjuvant chemo±radiotherapy Timing of adjuvant treatment (weeks from initial operation)c
“Leak” patients
Controls
62.4 ± 15.2 (47–79) 15 (60) 32.1 ± 3.4 (26–38)
61.4 ± 16.3 (45–80) 30 (60) 31.5 ± 3.7 (25–36)
p 0.8 1 0.57
1 (4) 9 (36) 13 (52) 2 (8)
5 (10) 20 (40) 23 (46) 2 (4)
0.7
4 (16) 10 (40) 11 (44)
8 (16) 20 (40) 22 (44)
1
9 (36) 8 (32) 8 (32) 5.3 ± 2.3 (2–11) 15 (60) 10 (40) 22 (88) 3 (12)a 17 (68) 8 (32) 0 (0) 22.5 ± 5.8 (12–35) 13 (52) 21 (84) (16/5) 21 (84) (16/5) 20 (80) (16/4) 13 (52) (10/3) 12 (48) 8.25 ± 2 (6–12)
22 (44) 10 (20) 18 (36) 5.7 ± 2.8 (2–12) 32 (64) 18 (36) 46 (92) 4 (8)b 30 (60) 18 (36) 2 (4) 9 ± 2.27 (6–15) 18 (36) 18 (36) (18/0) 13 (26) (13/0) 12 (24) (12/0) 1 (2) (1/0) 38 (76) 5.3 ± 0.9 (4–8)
0.5
0.5 0.9 0.88 0.84
0.0001 0.28 0.0002 0.0001 0.0001 0.0001 0.03 0.0003
Categorical variables are described as absolute numbers with percentages. Continuous variables are described as means ± SD (range of values). a One after intersphincteric resection. b Two after intersphincteric resections. c Time lapsed from the initial operation.
HRQoL Assessment and Tools
During their visit at a clinic dedicated to “Functional and Oncologic Surveillance for Colorectal Cancer” that operates on a weekly basis in the context of our Colorectal Unit, enrolled patients were asked to answer the HRQoL questionnaires by themselves with or without assistance from a family member at fixed postoperative assessment time points: 3, 6, and 12 months. At the end of the process, the involved team (1 colorectal surgeon, 1 psychologist, and 3 surgical residents) checked for the completeness of answers to the questionnaires. Illiteracy, low educational background, and vision problems were the reasons for the small percentage of patients who required assistance from a family member. Baseline assessment for obtaining preoperative HRQoL scores had taken place following the patients’ admission in the hospital, before any therapeutic intervention. Baseline HRQoL data were not available for the 4 patients who were not initially managed in our department. When appointments at the predetermined postoperative time points were not maintained, resched-
uling was done in a maximum of 2 weeks following the intended time or HRQoL data were obtained by phone. The latter was necessary in 4 postoperative assessments (5.3%) among the “leak” patients and in 10 postoperative assessments (6.6%) among the “no leak” patients. Patient HRQoL was evaluated by means of 4 validated questionnaires. The Medical Outcomes Study Short Form 36 (SF-36) uses 36 items to assess 8 different health quality-related domains, including general health perception (GH), physical functioning (PF), social functioning (SF), body pain, energy/fatigue, emotional well being, role limitations due to physical health (RLPH), and role limitations due to emotional problems (RLEP).18 The Gastrointestinal Quality of Life Index (GIQLI) is a favorite questionnaire for the assessment of the GI function. It includes 36 items in 5 categories (emotional and mental health, physical function, life and social role, symptoms, and treatment reaction). A 5-point Likert scale ranging from 0 (most negative) to 4 (most positive) is used for the scoring. “Global” GIQLI score is calculated by summariz-
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ing the points from all 36 questions, and its highest score is 144 points. Elevated scores translate to “better” HRQoL.19 The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 is composed of 5 multi-item functional scales that estimate physical, role, emotional, cognitive and social function, 1 global health status/quality of life scale, as well as 3 multi-item and 6 single-item symptomatic scales.20 High functional scores represent better functioning, whereas high symptom scores are related to more severe symptoms. The EORTC QLQ-CR29 is an updated module based on the EORTC QLQ-CR38 questionnaire and includes 29 questions, from which 2 are directed only to females or males and 9 questions are directed only to patients with stoma.21 The EORTC QLQ-CR29 questionnaire estimates mainly urinary symptoms, pain, fecal incontinence, stoma, and body image in a scale from 1 to 4 (1, not at all; 2, a little; 3, quite a bit; 4, very much). Statistical Analysis
Statistical analysis of demographic data and relevant clinical characteristics was performed by using the t test for continuous data and the Fisher exact test or χ2 test for categorical data. Differences between examined subgroups of patients (“leak” vs “no leak” patients) were analyzed by the Mann-Whitney U test. Statistical significance was set at p < 0.05. Statistical analysis was undertaken with SPSS statistical package version 16.0 (SPSS Inc, Chicago, IL).
RESULTS Demographic and most surgical data did not significantly differ between the studied groups (Table 1). As expected, “leak” patients required a longer hospitalization (p = 0.0001; Table 1). Although the numbers of initially constructed defunctioning loop ileostomies were not significantly different between “leak” and “no leak” groups, “leak” patients were required to remain with a stoma significantly more often at all postoperative assessment time points (3, 6, and 12 months). By the end of the first year, 13 (52%) of “leak” patients had not had their stoma reversed, because the administration of the 6- to 8-month-long adjuvant treatment was delayed and retardations were superimposed from health system availabilities (4 patients, all of them reversed by the 18th month after surgery), presence of a presacral sinus (1 patient, reversed by the end of the second year), development of anastomotic stricture (3 patients, reversed by the end of the second year), metastatic spread to lungs (1 patient, never reversed), and primary surgeons’ reluctance for end-colostomy reversal owing to a short rectal remnant or the likelihood for significant pelvic fibrosis precluding safe restoration of intestinal continuity (3 end stoma patients, never reversed). Chemotherapy was delayed and was administered in fewer “leak”
patients than in their "no leak" counterparts. Significant delays due to the leak-associated morbidity and patients’ refusal were mainly responsible for the omission of adjuvant treatment in an additional 6 stage II and III “leak” patients, who might have otherwise benefitted. No differences were observed at the baseline scores (preoperative status) between the 2 groups (analytical data not shown). Figures 1, 2 and 3 offer a graphic summary of the statistically significant postoperative differences at HRQoL variables between the “leak” patients and their peers without complications. Assessment at 3 Months
At 3 months after surgery, the patients with leaks had worse PF than those without leaks according to both GIQLI and EORTC-QLQ-C30 questionnaires (p = 0.03) (Figs. 2 and 3). EORTC QLQ-CR29 demonstrated a statistically significant difference in 3 items: “abdominal and pelvic pain” was more intense in “leak patients” (p = 0.03); “stoma- related problems” as well as “sore skin” appeared more frequently in patients with anastomotic leaks (p = 0.03 and p = 0.04) (Fig. 3). Assessment at 6 Months
At 6 months after surgery, SF-36 domain comparison revealed significantly worse RLPH (p = 0.01), RLEP (p = 0.02), SF (p = 0.008), and GH (p = 0.03) scores (Fig. 1). These data were consistent with the outcomes of GIQLI at the same time point. In particular, the global quality of life (p = 0.01) as well as the emotional and physical function (p = 0.008 and p = 0.004) deteriorated significantly in “leak” patients (Fig. 2). Physical functioning (p = 0.002) and overall quality of life (p = 0.005) also deteriorated in the latter group of patients, according to EORTC Q LQ-C30 (Fig. 3). Stoma problems and “sore skin,” as evaluated by EORTC QLQ-CR29, persisted at 6 months in the “leak” patients (p = 0.03; Fig. 3). Assessment at 12 Months
One year after colectomy according to SF-36, the “leak” patients still had a significant drop in PF (p = 0.04), RLPH (p = 0.001), RLEP (p = 0.003), SF (p = 0.009), and GH (p = 0.002) (Fig. 1). In line with this evidence, “leak” patients’ GIQLI “global” and emotional function scores were worse at 12 months (p = 0.005 and p = 0.007; Fig. 2). EORTC QLQ-C30 scores “agreed” at the worst level of overall quality of life for the “leak” patients (p = 0.004, Fig. 3). Finally, “leak” patients still reported “sore skin” more often (p = 0.005; Fig. 3).
DISCUSSION Functional restoration and preservation have long been incorporated among the goals of the “lege artis” colorec-
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SF-36
p = 0.001 p = 0.01
Role limitations due to emotional problems 100
60
40
40
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20
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m
on th s
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6
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p = 0.003
p = 0.002
p = 0.03
s
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se
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12 p = 0.008
p = 0.02
80
General health 100 p = 0.009
80
Ba
3
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m 6
3
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Social functioning 100
on th s
60
on th s
60
on th s
80
on th s
80
m
p = 0.04
Role limitations due to physical health 100
3
Physical functioning 100
FIGURE 1. Significant health-related quality-of-life differences between “leak” and “no leak” patients according to the SF-36 questionnaire. S F36 = Medical Outcomes Study Short Form 36.
tal surgical practice. The need for maintaining an optimal postoperative bowel and pelvic function came as a continuum to the higher rates of sphincter preservation. The advent of stapling devices, the wide adoption of total mesorectal excision, and the reduction of the oncologically “safe” distal margins have increased the risk of leaks from these low-lying “vulnerable” and technically demanding to construct anastomoses. Apart from its immediate negative impact on morbidity and recovery period, an anastomotic insufficiency may cause significant postoperative derangement in terms of the various HRQoL dimensions.11 Emotional and physical function difficulties arise as predominant discriminators between the “leak” and the "no leak" patients of our study throughout the first postoperative year. Our results reinforce the conclusions by Ashburn et al,11 which indicated that patients undergoing restorative proctectomy after anastomotic leak exhibit worse SF-36-assessed physical and mental function 6 months up to 3 years after surgery. In their study, worse HRQoL paralleled the negative effects of the leak and compromised bowel function, speculating a simultaneous downgrading of both components.11 EORTC QLQ-CR29, as used in our study, includes items referring to defecation problems.21 Nevertheless, because a proportionally large number of our “leak” patients
had not had their bowel continuity restored by the end of the first year, conclusive evidence on defecatory dysfunction cannot be easily derived by our sample of patients. Meanwhile, all other studies focusing on long-term functional outcome after low anterior resection anastomotic leaks had reported their results at 1 to 3 years follow-up and included patients with restored bowel continuity.8–11 Although sphincter function may be maintained, reduced neorectal and maximum tolerated volume, as well as increased frequency and urgency of bowel movements may predominate.8,9 Stoma reversal in a patient with a previous anastomotic leak may unveil the real long-term functional sequelae of the complication on anorectal function and the unavoidable declination of GI function-related quality of life. In addition, the leak itself as a complication appears to promote a negative impact on HRQoL during the time period the patient has to tolerate the presence of a “temporary” stoma and, simultaneously, to overcome the consequences of a complication. Indeed, in our study “general” scores of HRQoL were significantly worse for the “leak” patients at the 6- and 12-month assessment time points. Therefore, an adverse event such as the occurrence of an anastomotic leak, which, if successfully managed, may be a phenomenon of short duration physiologically
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GIQLI Emotional function 20
p = 0.008
p = 0.007
Physical function 25 p = 0.03
p = 0.004
p=0.03
20
15
15 10 10 5
on th s 12
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Global score 150 p = 0.005
p = 0.01 100
No leak Leak
th s 12
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se
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50
FIGURE 2. significant health-related quality-of-life differences between “leak” and “no leak” patients according to GIQLI questionnaire. GIQLI = Gastrointestinal Quality of Life Index.
and physically, does influence HRQoL at distant points in time. Patients’ HRQoL is influenced by their experiences and expectations.22 A negative treatment experience, such as an anastomotic leak, may result in a reduced estimate of HRQoL that extends beyond the time of the incident. The time-consuming treatment required for the management of the “leak” patients may further delay the return of their HRQoL to normal. So, it is reasonable to expect 6- and 12-month HRQoL score differences between the “leak” and the “no leak” patients. On average, patients with colorectal cancer may return to or even exceed their baseline HRQoL by 6 to 12 months.14–17 The “leak” patients do not prove to be able either to achieve such a restoration of their “precancer” HRQoL or to experience “reframing” of their life perspectives and psychological self-esteem enhancement, as their peers without complications.14,17 “Leak” patients experienced more “stoma” problems and “sore skin” around the stoma site. Although the rates of initially constructed “protective” loop ileostomy rates did not differ between “leak” and “no leak” patients, a proportionally larger number of “leak” patients had to live with a stoma for a significantly longer period of time. This is due to the delay of closure of initially or newly construct-
ed loop ileostomies and the reversal of end colostomies in the “leak” group of patients. In addition, the “expected” and usually well-planned ileostomy closure time in the group of patients without complications may have exerted a “soothing” effect on them. “No leak” patients may have easily overlooked common problems associated with the stoma presence, because they were informed of their temporary nature and disappearance of any inconveniences after the ileostomy closure. On the other hand, “leak” patients were obliged to bear either a nonpreviously anticipated stoma or to put up with the long presence of a potentially nonreversible stoma. Moreover, the emergently constructed stomas in our cases may account for the worse outcome as far as the problems related to them are concerned. Conditions relevant to a life-saving operation performed after an anastomotic leak, without a well-planned stoma marking and appropriate preparations may cause the “sore skin” in the “leak” patients. Delayed adjuvant treatment administration held back ileostomy closure scheduling in “leak” patients. In addition, a number of “leak” patients with unresolved leak-associated problems continued to have their stoma by the end of the first year. The presence of stoma at this time point may have further
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EORTC QLQ-C30 Global health status/QOL p = 0.005
100
Ba se
lin e
on th s m 12
6
m 3
m
lin e Ba se
Abdominal and pelvic pain 2.0 p = 0.003
EORTC QLQ-CR29 Stom-related problems 80 p = 0.003 p = 0.002
1.5
60
1.0
m
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p = 0.004
on th s
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p = 0.002
on th s
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p = 0.008
3
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Physical functioning
Sore skin 50
p = 0.005
p = 0.04
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p = 0.03
30
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s 12
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No leak Leak
FIGURE 3. Significant health-related quality-of-life differences between “leak” and “no leak” patients according to EORTC QLQ questionnaires. EORTC QLQ = European Organization of Research and Treatment of Cancer Quality of Life Questionnaire.
precluded HRQoL restoration to the desired and expected levels for a patient with rectal cancer 1 year after surgery. The coverage of the anastomosis by means of a diverting ileostomy construction had not necessarily decreased the rate of the leaks in our cohort of a limited number of patients. Instead, it appeared that it decreased the severity of the clinical presentation, and none of the initially diverted “leak” patients required a major reoperation. Indeed, despite the lack of effect of a diverting stoma on the reduction of leak rates, its presence protects from catastrophic sequelae and reoperations.23,24 The intraoperatively placed pelvic drain output revealed the leak in patients who might otherwise have had minimal or no systematic symptoms. On the other hand, both the defunctioning stoma and the drain may have changed the pattern of leaks’ clinical appearance from severe to mild and may have asserted a “protective” effect against potential postpelvic sepsis fibrosis, which would further impair function and, potentially, HRQoL. The debilitating side effects of stomas in the “leak” patients were not counteracted by the potentially deleterious
effects of the adjuvant treatment that a highest proportion of control patients were subjected to.17 The incidence of the anastomotic leak caused either delays or even omission of adjuvant treatment administration in a fraction of patients who would have otherwise potentially benefitted. Along with the increased potential for peritoneal and systematic cancer spread, such an occurrence may adversely reinforce the oncologic impact an anastomotic leak may have on patients with rectal cancer.3,5–7 Up to now, only 2 studies have reported on the negative effect of colorectal cancer surgery complications on assessment tool-measured HRQoL without focusing specifically on anastomotic leaks,12,13 and only one has explored the effects of anastomotic leaks on HRQoL.11 In comparison with these previous reports, the strength of our study lies at the multiplicity of HRQoL questionnaires applied, its case-matched design, and the repetitive measure of the HRQoL parameters at fixed assessment time points. In these terms, the current study may counteract the vacuum existing for a detailed, repetitive, and in-depth evaluation of HRQoL during the first year, when strate-
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gies targeting HRQoL improvements may need to be instituted. On the other hand, the rather limited number of patients remains a limitation for the present study. Due to the incidence of the anastomotic leaks in the particular group of patients with rectal cancer, an urgent need exists for larger-scale studies with greater patient samples that could provide results with more significant clinical value in assisting decision making and individualized treatment. Considering that the focus of the current study was on anastomotic leak and its impact on HRQoL, matching only for a limited number of parameters may not have allowed for an adequate exploration of the impact of the “leak” on the outcomes of interest. Several variables, such as tumor level and anastomosis, the use of a reservoir, the rate of initially constructed ileostomies, and others may have been implicated in HRQoL results. The small numbers and a type II error may have been responsible for the absence of a detected difference among these variables potentially affecting HRQoL. This potential drawback could have been circumvented by a number of subset analyses, but that would have led to a significant reduction in the number of subgroup patients after stratification. A larger study would be more reliable in assessing multiple relevant predictors for worse HRQoL. Restricting the follow-up assessments only at the first postoperative year may be considered as a drawback, but this is the particular time frame that a prospective in-person close follow-up is easily feasible. During this time period, the postcolectomy cancer patients remain still attached to the surgical team and are appropriately convinced to comply with a fixed appointment schedule until they feel fully recuperated. Personal assignments to members of the highly motivated research team involved for the specific data collection, the close monitoring of follow-up appointments, and the frequent phone contacts with patients for maintaining their predetermined appointments, as well as the lack of any patient financial obligations for their visits in the research-oriented HRQoL clinic, favored the implementation of a strict protocol for minimization of the targeted follow-up information loss. In our perception, the major drawback of studies focusing on conditions such as the anastomotic leaks is the heterogeneity of the patients themselves. This is based on the complication diversity in regard to its presentation, its severity, and its management. The physiologic and functional effects may not be the same in the patient who required just the drain to remain and the ileostomy to be closed at a later time and the one who had to be taken to the operating room on an emergent basis and had to tolerate an end potentially nonreversible stoma. Nowadays, functional results and HRQoL have gained a place among surgical outcome measures. Better HRQoL should be provided when possible to achieve optimal postoperative patient care. Health-related
quality-of-life outcome data may assist in identifying a vulnerable group of patients at risk who might require more intensive follow-up and the expertise of ancillary supportive services, such as that of an experienced psychologist, a specialized stoma nurse, or any relevant care provider who is implicated in a multidimensional approach for such patients. Patients who have anastomotic leaks may constitute such a group of patients who may need surveillance for at least 12 months postoperatively and the provision of expert support whenever available, so as to overcome the observed HRQoL defects. By no means can definitive conclusions be derived based only on the results of the current study. Evidence should rather be added to the limited reports on this intriguing topic to trigger the interest for undertaking similar, preferably multicentric, HRQoL studies at international high-volume rectal cancer institutions. These studies would further demonstrate the real impact a complication might have on this group of patients in terms of their posttreatment life quality and would institute guiding principles for management. REFERENCES 1. Alves A, Panis Y, Trancart D, Regimbeau JM, Pocard M, Valleur P. Factors associated with clinically significant anastomotic leakage after large bowel resection: multivariate analysis of 707 patients. World J Surg. 2002;26:499–502. 2. Mäkelä JT, Kiviniemi H, Laitinen S. Risk factors for anastomotic leakage after left-sided colorectal resection with rectal anastomosis. Dis Colon Rectum. 2003;46:653–660. 3. Walker KG, Bell SW, Rickard MJ, et al. Anastomotic leakage is predictive of diminished survival after potentially curative resection for colorectal cancer. Ann Surg. 2004;240:255–259. 4. Golub R, Golub RW, Cantu R Jr, Stein HD. A multivariate analysis of factors contributing to leakage of intestinal anastomoses. J Am Coll Surg. 1997;184:364–372. 5. Eberhardt JM, Kiran RP, Lavery IC. The impact of anastomotic leak and intra-abdominal abscess on cancer-related outcomes after resection for colorectal cancer: a case control study. Dis Colon Rectum. 2009;52:380–386. 6. Mirnezami A, Mirnezami R, Chandrakumaran K, Sasapu K, Sagar P, Finan P. Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg. 2011;253:890–899. 7. McArdle CS, McMillan DC, Hole DJ. Impact of anastomotic leakage on long-term survival of patients undergoing curative resection for colorectal cancer. Br J Surg. 2005;92:1150–1154. 8. Hallböök O, Sjödahl R. Anastomotic leakage and functional outcome after anterior resection of the rectum. Br J Surg. 1996;83:60–62. 9. Nesbakken A, Nygaard K, Lunde OC. Outcome and late functional results after anastomotic leakage following mesorectal excision for rectal cancer. Br J Surg. 2001;88:400–404. 10. Bittorf B, Stadelmaier U, Merkel S, Hohenberger W, Matzel KE. Does anastomotic leakage affect functional outcome after rectal resection for cancer? Langenbecks Arch Surg. 2003;387:406–410.
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11. Ashburn JH, Stocchi L, Kiran RP, Dietz DW, Remzi FH. Consequences of anastomotic leak after restorative proctectomy for cancer: effect on long-term function and quality of life. Dis Colon Rectum. 2013;56:275–280. 12. Stucky CC, Pockaj BA, Novotny PJ, et al. Long-term follow-up and individual item analysis of quality of life assessments related to laparoscopic-assisted colectomy in the COST trial 9346-53 (INT 0146). Ann Surg Oncol. 2011;18:2422–2431. 13. Anthony T, Long J, Hynan LS, et al. Surgical complications exert a lasting effect on disease-specific health-related quality of life for patients with colorectal cancer. Surgery. 2003;134:119–125. 14. Camilleri-Brennan J, Steele RJ. Prospective analysis of quality of life and survival following mesorectal excision for rectal cancer. Br J Surg. 2001;88:1617–1622. 15. Arndt V, Merx H, Stegmaier C, Ziegler H, Brenner H. Quality of life in patients with colorectal cancer 1 year after diagnosis compared with the general population: a population-based study. J Clin Oncol. 2004;22:4829–4836. 16. Theodoropoulos GE, Karantanos T, Stamopoulos P, Zografos G. Prospective evaluation of health-related quality of life after laparoscopic colectomy for cancer. Tech Coloproctol. 2013;17:27–38. 17. Theodoropoulos GE, Papailiou JG, Stamopoulos PL, et al. Prospective evaluation of health-related quality of life in a homogeneous Mediterranean group of colorectal cancer patients. Am Surg. 2010;76:502–508.
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18. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–196. 19. Eypasch E, Williams JI, Wood-Dauphinee S, et al. Gastrointestinal Quality of Life Index: development, validation and application of a new instrument. Br J Surg. 1995;82:216–222. 20. Schwenk W, Neudecker J, Haase O, Raue W, Strohm T, Müller JM. Comparison of EORTC quality of life core questionnaire (EORTC-QLQ-C30) and gastrointestinal quality of life index (GIQLI) in patients undergoing elective colorectal cancer resection. Int J Colorectal Dis. 2004;19:554–560. 21. Peng J, Shi D, Goodman KA, et al. Early results of quality of life for curatively treated rectal cancers in Chinese patients with EORTC QLQ-CR29. Radiat Oncol. 2011;6:93. 22. Bernhard J, Hürny C, Maibach R, Herrmann R, Laffer U. Quality of life as subjective experience: reframing of perception in patients with colon cancer undergoing radical resection with or without adjuvant chemotherapy. Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol. 1999;10:775–782. 23. Tan WS, Tang CL, Shi L, Eu KW. Meta-analysis of defunctioning stomas in low anterior resection for rectal cancer. Br J Surg. 2009;96:462–472. 24. Wong NY, Eu KW. A defunctioning ileostomy does not prevent clinical anastomotic leak after a low anterior resection: a prospective, comparative study. Dis Colon Rectum. 2005;48:2076–2079.
Do Anastomotic Leaks Impair Postoperative Health-related Quality of Life After Rectal Cancer Surgery? A Case-matched Study Annezo Marinatou, M.D. • George E. Theodoropoulos, M.D., Ph.D. Styliani Karanika, M.D. • Theodoros Karantanos, M.D. • Spiridon Siakavellas, M.D. Basileios G. Spyropoulos M.D., Ph.D. • Konstantinos Toutouzas, M.D., Ph.D. George Zografos, M.D., Ph.D. Colorectal Unit, First Department of Propaedeutic Surgery, Athens Medical School, Athens, Greece
BACKGROUND: Anastomotic leaks after colorectal resections for cancer are a leading cause of postoperative morbidity, mortality, and long hospital stay. Few data exist on the potentially deleterious effect of the anastomotic leaks after proctectomy for cancer on patient health-related quality of life.
36, Gastrointestinal Quality of Life Index, European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-C30, and European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-CR29).
OBJECTIVE: The aim of this study was to explore the
hospitalization. Although the numbers of initially constructed defunctioning loop ileostomies were not significantly different between cases and controls, “leak” patients were required to remain with a stoma significantly more often at all postoperative assessment time points. No differences were observed in the baseline scores between the 2 groups. Physical function of “leak” patients was significantly worse at all postoperative assessment time points. At 6 and 12 months, their emotional and social function and overall q uality-oflife scores were significantly decreased in comparison with the patients with an uncomplicated course. “Leak” patients experienced significantly more “stoma-related problems” and “sore skin” around the stoma site.
effect of clinically evident anastomotic leaks on h ealthrelated quality of life after rectal cancer excision. DESIGN: This is a case-matched study. SETTINGS: This study was conducted in a Greek academic surgical department. PATIENTS: Included were 25 patients undergoing low
anterior resection complicated by an anastomotic leak (Clavien classification II, n = 14, and III, n = 11) and 50 patients undergoing low anterior resection with an uncomplicated course. MAIN OUTCOME MEASURES: Health-related quality-of-life data were prospectively collected at fixed assessment time points (baseline, 3, 6, and 12 months postoperatively) by the use of validated questionnaires (Medical Outcomes Study Short Form Financial Disclosure: None reported. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Phoenix, AZ, April 27 to May 1, 2013. Correspondence: George E. Theodoropoulos, M.D., Ph.D., Athens Medical School, 7 Semitelou St, GR-11528 Athens, Greece. E-mail: [email protected] Dis Colon Rectum 2014; 57: 158–166 DOI: 10.1097/DCR.0000000000000040 © The ASCRS 2014
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RESULTS: “Leak” patients required a longer
LIMITATIONS: Limited number of patients, restriction of follow-up to the end of the first year, and heterogeneity in terms of the presentation, severity, and management of anastomotic leaks were the limitations of this study. CONCLUSIONS: Anastomotic leaks have an adverse effect on postoperative health-related quality of life.
KEY WORDS: Colorectal cancer; Anastomotic leak;
Health-related quality of life; Medical Outcomes Study Short Form 36; Gastrointestinal Quality of life Index; European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-C30. Diseases of the Colon & Rectum Volume 57: 2 (2014)
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A
nastomotic dehiscence after colorectal resections is recognized as a leading cause of postoperative morbidity, mortality, and long hospital stay.1–4 Its prognostic relevance for adverse oncologic outcomes is included among its disastrous consequences.5–7 Long-term functional derangement after restorative rectal excisions complicated by anastomotic leaks has been reported in rather limited previous studies.8–11 Health-related quality of life (HRQoL) has been established as an important outcome measure of surgical treatment success and may be closely related and directly affected by functional disorders arising from a postoperative complication, such as an anastomotic failure.11 Postcolectomy complications have been associated with worse HRQoL in patients with colorectal cancer.12,13 Nevertheless, only 1 recently published series has eloquently addressed the potentially deleterious effect of the anastomotic leaks after proctectomy for cancer on patients’ long-term HRQoL.11 Health-related quality of life after colorectal resections for malignancy can usually be restored up to the end of the first postoperative year.14–17 Stressing factors such as the physical and emotional adaptation after the surgical and psychological trauma, the administration of adjuvant treatment with deleterious side effects, and the need to tolerate a reversible, potentially temporary stoma until anastomosis is well healed are usually all entirely accumulated during the time period of the first year following surgery. In the present study, our null hypothesis was that anastomotic leaks after low anterior resections for cancer do not affect HRQoL during the first postoperative year. Therefore, in an effort to show the impact of anastomotic leaks on common HRQoL domains, we conducted a case-matched study between patients who experienced a symptomatic anastomotic leak after rectal resection for cancer and patients with an uneventful recovery.
METHODS Patients and Data Collection
In this retrospective case-matched study, data were derived from a prospectively collected and maintained, institutional review board-approved, clinical and HRQoL database on patients who have biopsy-proven colorectal cancer and who were surgically managed between 2007 and 2012 at the First Department of Propaedeutic Surgery of Athens Medical School. Documentation of demographic, clinical, operative, postoperative, and pathologic characteristics was performed in detail. Twenty-five patients with clinically evident anastomotic leak after a restorative rectal cancer operation with therapeutic intent were selected. Four of them had been referred from other institutions after the occurrence of the leak, and 5 of them had been fully managed in a neighboring nonacademic department of the same hospital, but they were followed up in terms
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of HRQoL by our colorectal unit. The “leak” patients were age (±5 years), sex, and stage matched in a 1:2 fashion with 50 patients who had rectal cancer with an uncomplicated course, who were retrieved from a cohort of 350 patients who had undergone colorectal resection for neoplasms during the same time period. An independent reviewer, who was blinded to all clinical data except the matching criteria, matched the patients manually one by one on the basis of these variables. Patients’ features and clinical details are depicted in Table 1. Patients younger than 18 and older than 80 years, with distant metastatic disease at presentation, initially managed on an emergency basis and with a history of IBD or hereditary cancer were not included. The standard operative technique included total mesorectal excision in patients with tumors in the lower and mid rectum, and partial mesorectal excision with transection of the mesorectum at least 5 cm distal to the tumor in patients with cancer of the upper rectum. A defunctioning “protective” loop ileostomy was constructed as preferred by the surgeon in the majority of the cases where a low-lying anastomosis was necessary. In the 25 patients without complications, the cardinal clinical findings that led to suspicion and/or diagnosis of the anastomotic leak were the following: peritonitis (9 patients), purulent and/ or feculent material from the intraoperative placed pelvic drain (5 patients, all with initial diverting stoma), fever with or without “pelvic” pain (5 patients, 3 of them with initial diverting stoma), protracted ileus (3 patients, all with initial diverting stoma), drainage per rectum (2 patients, 1 with initial diverting stoma), and rectovaginal fistula (1 patient, with initial diverting stoma). Confirmation of the anastomotic insufficiency was obtained by CT and/or a contrast medium exploration (Gastrografin) in 18 patients. Fourteen anastomotic leaks were classified according to Clavien complication classification as grade II (not requiring interventional treatment), and 11 of them were classified as grade III (requiring surgical, endoscopic, or radiologic intervention).18 The management of anastomotic leak included primarily conservative measures consisting of the maintenance of the intraoperatively placed pelvic drain (3–6 weeks) (12 cases, all with initial loop ileostomy) and spontaneous transrectal drainage (2 cases, 1 with initial loop ileostomy), as well as CT-guided placement of a presacral drain (1 case); relaparotomy, lavage, and pelvic drain placement (2 cases); relaparotomy, lavage, and loop ileostomy (3 cases); and relaparotomy with takedown of anastomosis and end colostomy construction (5 cases). Although preoperative marking was the standard practice for all electively constructed ileostomies, an appropriate stoma marking did not precede the 8 emergently constructed stomas in the operative management of the leaks.
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TABLE 1. Characteristics and treatment-related factors of patients with and without anastomotic leak
Age Sex, male BMI ASA classification ASA I ASA II ASA III ASA IV Tumor stage I II III Tumor location Upper rectum Mid rectum Lower rectum Level of anastomosis, cm from anal verge Type of anastomosis Colorectal Coloanal Stapled Handsewn End-to-end Colonic J-pouch Transverse coloplasty Total days of hospitalization Protective loop ileostomy at initial operation Presence of stoma at discharge (loop ileostomy/end colostomy) Presence of stoma at 3 mo (loop ileostomy/end colostomy) Presence of stoma at 6 mo (loop ileostomy/end colostomy) Presence of stoma at 12 mo (loop ileostomy/end colostomy) Adjuvant chemo±radiotherapy Timing of adjuvant treatment (weeks from initial operation)c
“Leak” patients
Controls
62.4 ± 15.2 (47–79) 15 (60) 32.1 ± 3.4 (26–38)
61.4 ± 16.3 (45–80) 30 (60) 31.5 ± 3.7 (25–36)
p 0.8 1 0.57
1 (4) 9 (36) 13 (52) 2 (8)
5 (10) 20 (40) 23 (46) 2 (4)
0.7
4 (16) 10 (40) 11 (44)
8 (16) 20 (40) 22 (44)
1
9 (36) 8 (32) 8 (32) 5.3 ± 2.3 (2–11) 15 (60) 10 (40) 22 (88) 3 (12)a 17 (68) 8 (32) 0 (0) 22.5 ± 5.8 (12–35) 13 (52) 21 (84) (16/5) 21 (84) (16/5) 20 (80) (16/4) 13 (52) (10/3) 12 (48) 8.25 ± 2 (6–12)
22 (44) 10 (20) 18 (36) 5.7 ± 2.8 (2–12) 32 (64) 18 (36) 46 (92) 4 (8)b 30 (60) 18 (36) 2 (4) 9 ± 2.27 (6–15) 18 (36) 18 (36) (18/0) 13 (26) (13/0) 12 (24) (12/0) 1 (2) (1/0) 38 (76) 5.3 ± 0.9 (4–8)
0.5
0.5 0.9 0.88 0.84
0.0001 0.28 0.0002 0.0001 0.0001 0.0001 0.03 0.0003
Categorical variables are described as absolute numbers with percentages. Continuous variables are described as means ± SD (range of values). a One after intersphincteric resection. b Two after intersphincteric resections. c Time lapsed from the initial operation.
HRQoL Assessment and Tools
During their visit at a clinic dedicated to “Functional and Oncologic Surveillance for Colorectal Cancer” that operates on a weekly basis in the context of our Colorectal Unit, enrolled patients were asked to answer the HRQoL questionnaires by themselves with or without assistance from a family member at fixed postoperative assessment time points: 3, 6, and 12 months. At the end of the process, the involved team (1 colorectal surgeon, 1 psychologist, and 3 surgical residents) checked for the completeness of answers to the questionnaires. Illiteracy, low educational background, and vision problems were the reasons for the small percentage of patients who required assistance from a family member. Baseline assessment for obtaining preoperative HRQoL scores had taken place following the patients’ admission in the hospital, before any therapeutic intervention. Baseline HRQoL data were not available for the 4 patients who were not initially managed in our department. When appointments at the predetermined postoperative time points were not maintained, resched-
uling was done in a maximum of 2 weeks following the intended time or HRQoL data were obtained by phone. The latter was necessary in 4 postoperative assessments (5.3%) among the “leak” patients and in 10 postoperative assessments (6.6%) among the “no leak” patients. Patient HRQoL was evaluated by means of 4 validated questionnaires. The Medical Outcomes Study Short Form 36 (SF-36) uses 36 items to assess 8 different health quality-related domains, including general health perception (GH), physical functioning (PF), social functioning (SF), body pain, energy/fatigue, emotional well being, role limitations due to physical health (RLPH), and role limitations due to emotional problems (RLEP).18 The Gastrointestinal Quality of Life Index (GIQLI) is a favorite questionnaire for the assessment of the GI function. It includes 36 items in 5 categories (emotional and mental health, physical function, life and social role, symptoms, and treatment reaction). A 5-point Likert scale ranging from 0 (most negative) to 4 (most positive) is used for the scoring. “Global” GIQLI score is calculated by summariz-
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ing the points from all 36 questions, and its highest score is 144 points. Elevated scores translate to “better” HRQoL.19 The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 is composed of 5 multi-item functional scales that estimate physical, role, emotional, cognitive and social function, 1 global health status/quality of life scale, as well as 3 multi-item and 6 single-item symptomatic scales.20 High functional scores represent better functioning, whereas high symptom scores are related to more severe symptoms. The EORTC QLQ-CR29 is an updated module based on the EORTC QLQ-CR38 questionnaire and includes 29 questions, from which 2 are directed only to females or males and 9 questions are directed only to patients with stoma.21 The EORTC QLQ-CR29 questionnaire estimates mainly urinary symptoms, pain, fecal incontinence, stoma, and body image in a scale from 1 to 4 (1, not at all; 2, a little; 3, quite a bit; 4, very much). Statistical Analysis
Statistical analysis of demographic data and relevant clinical characteristics was performed by using the t test for continuous data and the Fisher exact test or χ2 test for categorical data. Differences between examined subgroups of patients (“leak” vs “no leak” patients) were analyzed by the Mann-Whitney U test. Statistical significance was set at p < 0.05. Statistical analysis was undertaken with SPSS statistical package version 16.0 (SPSS Inc, Chicago, IL).
RESULTS Demographic and most surgical data did not significantly differ between the studied groups (Table 1). As expected, “leak” patients required a longer hospitalization (p = 0.0001; Table 1). Although the numbers of initially constructed defunctioning loop ileostomies were not significantly different between “leak” and “no leak” groups, “leak” patients were required to remain with a stoma significantly more often at all postoperative assessment time points (3, 6, and 12 months). By the end of the first year, 13 (52%) of “leak” patients had not had their stoma reversed, because the administration of the 6- to 8-month-long adjuvant treatment was delayed and retardations were superimposed from health system availabilities (4 patients, all of them reversed by the 18th month after surgery), presence of a presacral sinus (1 patient, reversed by the end of the second year), development of anastomotic stricture (3 patients, reversed by the end of the second year), metastatic spread to lungs (1 patient, never reversed), and primary surgeons’ reluctance for end-colostomy reversal owing to a short rectal remnant or the likelihood for significant pelvic fibrosis precluding safe restoration of intestinal continuity (3 end stoma patients, never reversed). Chemotherapy was delayed and was administered in fewer “leak”
patients than in their "no leak" counterparts. Significant delays due to the leak-associated morbidity and patients’ refusal were mainly responsible for the omission of adjuvant treatment in an additional 6 stage II and III “leak” patients, who might have otherwise benefitted. No differences were observed at the baseline scores (preoperative status) between the 2 groups (analytical data not shown). Figures 1, 2 and 3 offer a graphic summary of the statistically significant postoperative differences at HRQoL variables between the “leak” patients and their peers without complications. Assessment at 3 Months
At 3 months after surgery, the patients with leaks had worse PF than those without leaks according to both GIQLI and EORTC-QLQ-C30 questionnaires (p = 0.03) (Figs. 2 and 3). EORTC QLQ-CR29 demonstrated a statistically significant difference in 3 items: “abdominal and pelvic pain” was more intense in “leak patients” (p = 0.03); “stoma- related problems” as well as “sore skin” appeared more frequently in patients with anastomotic leaks (p = 0.03 and p = 0.04) (Fig. 3). Assessment at 6 Months
At 6 months after surgery, SF-36 domain comparison revealed significantly worse RLPH (p = 0.01), RLEP (p = 0.02), SF (p = 0.008), and GH (p = 0.03) scores (Fig. 1). These data were consistent with the outcomes of GIQLI at the same time point. In particular, the global quality of life (p = 0.01) as well as the emotional and physical function (p = 0.008 and p = 0.004) deteriorated significantly in “leak” patients (Fig. 2). Physical functioning (p = 0.002) and overall quality of life (p = 0.005) also deteriorated in the latter group of patients, according to EORTC Q LQ-C30 (Fig. 3). Stoma problems and “sore skin,” as evaluated by EORTC QLQ-CR29, persisted at 6 months in the “leak” patients (p = 0.03; Fig. 3). Assessment at 12 Months
One year after colectomy according to SF-36, the “leak” patients still had a significant drop in PF (p = 0.04), RLPH (p = 0.001), RLEP (p = 0.003), SF (p = 0.009), and GH (p = 0.002) (Fig. 1). In line with this evidence, “leak” patients’ GIQLI “global” and emotional function scores were worse at 12 months (p = 0.005 and p = 0.007; Fig. 2). EORTC QLQ-C30 scores “agreed” at the worst level of overall quality of life for the “leak” patients (p = 0.004, Fig. 3). Finally, “leak” patients still reported “sore skin” more often (p = 0.005; Fig. 3).
DISCUSSION Functional restoration and preservation have long been incorporated among the goals of the “lege artis” colorec-
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SF-36
p = 0.001 p = 0.01
Role limitations due to emotional problems 100
60
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on th s
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th 12
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6
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p = 0.003
p = 0.002
p = 0.03
s
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s
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s
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se
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12 p = 0.008
p = 0.02
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General health 100 p = 0.009
80
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Social functioning 100
on th s
60
on th s
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on th s
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on th s
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m
p = 0.04
Role limitations due to physical health 100
3
Physical functioning 100
FIGURE 1. Significant health-related quality-of-life differences between “leak” and “no leak” patients according to the SF-36 questionnaire. S F36 = Medical Outcomes Study Short Form 36.
tal surgical practice. The need for maintaining an optimal postoperative bowel and pelvic function came as a continuum to the higher rates of sphincter preservation. The advent of stapling devices, the wide adoption of total mesorectal excision, and the reduction of the oncologically “safe” distal margins have increased the risk of leaks from these low-lying “vulnerable” and technically demanding to construct anastomoses. Apart from its immediate negative impact on morbidity and recovery period, an anastomotic insufficiency may cause significant postoperative derangement in terms of the various HRQoL dimensions.11 Emotional and physical function difficulties arise as predominant discriminators between the “leak” and the "no leak" patients of our study throughout the first postoperative year. Our results reinforce the conclusions by Ashburn et al,11 which indicated that patients undergoing restorative proctectomy after anastomotic leak exhibit worse SF-36-assessed physical and mental function 6 months up to 3 years after surgery. In their study, worse HRQoL paralleled the negative effects of the leak and compromised bowel function, speculating a simultaneous downgrading of both components.11 EORTC QLQ-CR29, as used in our study, includes items referring to defecation problems.21 Nevertheless, because a proportionally large number of our “leak” patients
had not had their bowel continuity restored by the end of the first year, conclusive evidence on defecatory dysfunction cannot be easily derived by our sample of patients. Meanwhile, all other studies focusing on long-term functional outcome after low anterior resection anastomotic leaks had reported their results at 1 to 3 years follow-up and included patients with restored bowel continuity.8–11 Although sphincter function may be maintained, reduced neorectal and maximum tolerated volume, as well as increased frequency and urgency of bowel movements may predominate.8,9 Stoma reversal in a patient with a previous anastomotic leak may unveil the real long-term functional sequelae of the complication on anorectal function and the unavoidable declination of GI function-related quality of life. In addition, the leak itself as a complication appears to promote a negative impact on HRQoL during the time period the patient has to tolerate the presence of a “temporary” stoma and, simultaneously, to overcome the consequences of a complication. Indeed, in our study “general” scores of HRQoL were significantly worse for the “leak” patients at the 6- and 12-month assessment time points. Therefore, an adverse event such as the occurrence of an anastomotic leak, which, if successfully managed, may be a phenomenon of short duration physiologically
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GIQLI Emotional function 20
p = 0.008
p = 0.007
Physical function 25 p = 0.03
p = 0.004
p=0.03
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on th s 12
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p = 0.01 100
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th s 12
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FIGURE 2. significant health-related quality-of-life differences between “leak” and “no leak” patients according to GIQLI questionnaire. GIQLI = Gastrointestinal Quality of Life Index.
and physically, does influence HRQoL at distant points in time. Patients’ HRQoL is influenced by their experiences and expectations.22 A negative treatment experience, such as an anastomotic leak, may result in a reduced estimate of HRQoL that extends beyond the time of the incident. The time-consuming treatment required for the management of the “leak” patients may further delay the return of their HRQoL to normal. So, it is reasonable to expect 6- and 12-month HRQoL score differences between the “leak” and the “no leak” patients. On average, patients with colorectal cancer may return to or even exceed their baseline HRQoL by 6 to 12 months.14–17 The “leak” patients do not prove to be able either to achieve such a restoration of their “precancer” HRQoL or to experience “reframing” of their life perspectives and psychological self-esteem enhancement, as their peers without complications.14,17 “Leak” patients experienced more “stoma” problems and “sore skin” around the stoma site. Although the rates of initially constructed “protective” loop ileostomy rates did not differ between “leak” and “no leak” patients, a proportionally larger number of “leak” patients had to live with a stoma for a significantly longer period of time. This is due to the delay of closure of initially or newly construct-
ed loop ileostomies and the reversal of end colostomies in the “leak” group of patients. In addition, the “expected” and usually well-planned ileostomy closure time in the group of patients without complications may have exerted a “soothing” effect on them. “No leak” patients may have easily overlooked common problems associated with the stoma presence, because they were informed of their temporary nature and disappearance of any inconveniences after the ileostomy closure. On the other hand, “leak” patients were obliged to bear either a nonpreviously anticipated stoma or to put up with the long presence of a potentially nonreversible stoma. Moreover, the emergently constructed stomas in our cases may account for the worse outcome as far as the problems related to them are concerned. Conditions relevant to a life-saving operation performed after an anastomotic leak, without a well-planned stoma marking and appropriate preparations may cause the “sore skin” in the “leak” patients. Delayed adjuvant treatment administration held back ileostomy closure scheduling in “leak” patients. In addition, a number of “leak” patients with unresolved leak-associated problems continued to have their stoma by the end of the first year. The presence of stoma at this time point may have further
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MARINATOU ET AL: ANASTOMOTIC LEAKS AND QUALITY OF LIFE
EORTC QLQ-C30 Global health status/QOL p = 0.005
100
Ba se
lin e
on th s m 12
6
m 3
m
lin e Ba se
Abdominal and pelvic pain 2.0 p = 0.003
EORTC QLQ-CR29 Stom-related problems 80 p = 0.003 p = 0.002
1.5
60
1.0
m
20
12
20
p = 0.004
on th s
40
m
40
6
60
p = 0.002
on th s
60
on th s
80
on th s
80
m
p = 0.008
3
100
on th s
Physical functioning
Sore skin 50
p = 0.005
p = 0.04
40
p = 0.03
30
40
20 20
s 12
m
on
th
s 6
m
on
th
s m
on
th
s 12
m
on
th
s th m 6
3
m
on
th on m 12
on
th
s
s th on m 6
on m 3
Ba
se
lin
th
e
s
s
10
3
0.5
No leak Leak
FIGURE 3. Significant health-related quality-of-life differences between “leak” and “no leak” patients according to EORTC QLQ questionnaires. EORTC QLQ = European Organization of Research and Treatment of Cancer Quality of Life Questionnaire.
precluded HRQoL restoration to the desired and expected levels for a patient with rectal cancer 1 year after surgery. The coverage of the anastomosis by means of a diverting ileostomy construction had not necessarily decreased the rate of the leaks in our cohort of a limited number of patients. Instead, it appeared that it decreased the severity of the clinical presentation, and none of the initially diverted “leak” patients required a major reoperation. Indeed, despite the lack of effect of a diverting stoma on the reduction of leak rates, its presence protects from catastrophic sequelae and reoperations.23,24 The intraoperatively placed pelvic drain output revealed the leak in patients who might otherwise have had minimal or no systematic symptoms. On the other hand, both the defunctioning stoma and the drain may have changed the pattern of leaks’ clinical appearance from severe to mild and may have asserted a “protective” effect against potential postpelvic sepsis fibrosis, which would further impair function and, potentially, HRQoL. The debilitating side effects of stomas in the “leak” patients were not counteracted by the potentially deleterious
effects of the adjuvant treatment that a highest proportion of control patients were subjected to.17 The incidence of the anastomotic leak caused either delays or even omission of adjuvant treatment administration in a fraction of patients who would have otherwise potentially benefitted. Along with the increased potential for peritoneal and systematic cancer spread, such an occurrence may adversely reinforce the oncologic impact an anastomotic leak may have on patients with rectal cancer.3,5–7 Up to now, only 2 studies have reported on the negative effect of colorectal cancer surgery complications on assessment tool-measured HRQoL without focusing specifically on anastomotic leaks,12,13 and only one has explored the effects of anastomotic leaks on HRQoL.11 In comparison with these previous reports, the strength of our study lies at the multiplicity of HRQoL questionnaires applied, its case-matched design, and the repetitive measure of the HRQoL parameters at fixed assessment time points. In these terms, the current study may counteract the vacuum existing for a detailed, repetitive, and in-depth evaluation of HRQoL during the first year, when strate-
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gies targeting HRQoL improvements may need to be instituted. On the other hand, the rather limited number of patients remains a limitation for the present study. Due to the incidence of the anastomotic leaks in the particular group of patients with rectal cancer, an urgent need exists for larger-scale studies with greater patient samples that could provide results with more significant clinical value in assisting decision making and individualized treatment. Considering that the focus of the current study was on anastomotic leak and its impact on HRQoL, matching only for a limited number of parameters may not have allowed for an adequate exploration of the impact of the “leak” on the outcomes of interest. Several variables, such as tumor level and anastomosis, the use of a reservoir, the rate of initially constructed ileostomies, and others may have been implicated in HRQoL results. The small numbers and a type II error may have been responsible for the absence of a detected difference among these variables potentially affecting HRQoL. This potential drawback could have been circumvented by a number of subset analyses, but that would have led to a significant reduction in the number of subgroup patients after stratification. A larger study would be more reliable in assessing multiple relevant predictors for worse HRQoL. Restricting the follow-up assessments only at the first postoperative year may be considered as a drawback, but this is the particular time frame that a prospective in-person close follow-up is easily feasible. During this time period, the postcolectomy cancer patients remain still attached to the surgical team and are appropriately convinced to comply with a fixed appointment schedule until they feel fully recuperated. Personal assignments to members of the highly motivated research team involved for the specific data collection, the close monitoring of follow-up appointments, and the frequent phone contacts with patients for maintaining their predetermined appointments, as well as the lack of any patient financial obligations for their visits in the research-oriented HRQoL clinic, favored the implementation of a strict protocol for minimization of the targeted follow-up information loss. In our perception, the major drawback of studies focusing on conditions such as the anastomotic leaks is the heterogeneity of the patients themselves. This is based on the complication diversity in regard to its presentation, its severity, and its management. The physiologic and functional effects may not be the same in the patient who required just the drain to remain and the ileostomy to be closed at a later time and the one who had to be taken to the operating room on an emergent basis and had to tolerate an end potentially nonreversible stoma. Nowadays, functional results and HRQoL have gained a place among surgical outcome measures. Better HRQoL should be provided when possible to achieve optimal postoperative patient care. Health-related
quality-of-life outcome data may assist in identifying a vulnerable group of patients at risk who might require more intensive follow-up and the expertise of ancillary supportive services, such as that of an experienced psychologist, a specialized stoma nurse, or any relevant care provider who is implicated in a multidimensional approach for such patients. Patients who have anastomotic leaks may constitute such a group of patients who may need surveillance for at least 12 months postoperatively and the provision of expert support whenever available, so as to overcome the observed HRQoL defects. By no means can definitive conclusions be derived based only on the results of the current study. Evidence should rather be added to the limited reports on this intriguing topic to trigger the interest for undertaking similar, preferably multicentric, HRQoL studies at international high-volume rectal cancer institutions. These studies would further demonstrate the real impact a complication might have on this group of patients in terms of their posttreatment life quality and would institute guiding principles for management. REFERENCES 1. Alves A, Panis Y, Trancart D, Regimbeau JM, Pocard M, Valleur P. Factors associated with clinically significant anastomotic leakage after large bowel resection: multivariate analysis of 707 patients. World J Surg. 2002;26:499–502. 2. Mäkelä JT, Kiviniemi H, Laitinen S. Risk factors for anastomotic leakage after left-sided colorectal resection with rectal anastomosis. Dis Colon Rectum. 2003;46:653–660. 3. Walker KG, Bell SW, Rickard MJ, et al. Anastomotic leakage is predictive of diminished survival after potentially curative resection for colorectal cancer. Ann Surg. 2004;240:255–259. 4. Golub R, Golub RW, Cantu R Jr, Stein HD. A multivariate analysis of factors contributing to leakage of intestinal anastomoses. J Am Coll Surg. 1997;184:364–372. 5. Eberhardt JM, Kiran RP, Lavery IC. The impact of anastomotic leak and intra-abdominal abscess on cancer-related outcomes after resection for colorectal cancer: a case control study. Dis Colon Rectum. 2009;52:380–386. 6. Mirnezami A, Mirnezami R, Chandrakumaran K, Sasapu K, Sagar P, Finan P. Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg. 2011;253:890–899. 7. McArdle CS, McMillan DC, Hole DJ. Impact of anastomotic leakage on long-term survival of patients undergoing curative resection for colorectal cancer. Br J Surg. 2005;92:1150–1154. 8. Hallböök O, Sjödahl R. Anastomotic leakage and functional outcome after anterior resection of the rectum. Br J Surg. 1996;83:60–62. 9. Nesbakken A, Nygaard K, Lunde OC. Outcome and late functional results after anastomotic leakage following mesorectal excision for rectal cancer. Br J Surg. 2001;88:400–404. 10. Bittorf B, Stadelmaier U, Merkel S, Hohenberger W, Matzel KE. Does anastomotic leakage affect functional outcome after rectal resection for cancer? Langenbecks Arch Surg. 2003;387:406–410.
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