Review Article

Smoking, Colorectal Disease and Colorectal Surgical Practice

David G^1#, West MA^2,3#, Magee CJ¹ and Walsh CJ^1*
1Department of Surgery, Wirral University Teaching Hospital NHS Foundation Trust, UK
²Academic Unit of Cancer Sciences, University of Southampton, UK
³Department of Surgery, University Hospital Southampton NHS Foundation Trust, UK
^#Both authors have contributed equally to this work

^*Corresponding author: Walsh CJ, Department of Surgery, Wirral University Teaching Hospital NHS Foundation Trust, Wirral, UK

Published: 15 Sep, 2016
Cite this article as: David G, West MA, Magee CJ, Walsh CJ. Smoking, Colorectal Disease and Colorectal Surgical Practice. Clin Surg. 2016; 1: 1115.

Abstract

Background: Cigarette smoking adversely affects the natural history of a number of common colorectal conditions and their treatment. Colorectal cancer is now recognised as a smoking attributable cancer.
Aim: This is a narrative review of the effects of cigarette smoking on colorectal disease, colorectal surgery and colorectal surgical outcomes.
Methods: Literature search was carried out for relevant articles highlighting relationship between smoking and variety of colorectal conditions (cancer, diverticular disease, inflammatory bowel disease and perianal diseases). As we wanted to highlight the breadth of the problem to current colorectal practice, we have deliberately kept this as a narrative review.
Results: Smoking is associated with higher all-cause mortality and colorectal cancer–specific mortality in non-metastatic colorectal cancer and it worsens the outcomes of a number of inflammatory colorectal conditions including diverticular disease and Crohn’s disease. Smoking impairs the inflammatory response, tissue repair and consequently impairs wound healing. Smoking during radiotherapy worsens acute toxicity and reduces disease free survival in anal cancer.
Conclusion: Approximately 10 million adults smoke cigarettes in Great Britain currently and therefore there is arguably no single greater reversible patient related parameter that affects outcomes in colorectal practice. Surgeons must advocate and facilitate smoking cessation in their patients putting particular emphasis on the likelihood of increased complication rates and poorer outcomes if an active smoker undergoes colorectal surgery or radiotherapy.
Keywords: Smoking; Colorectal Disease; WHO

Introduction

In 1887 Thomas Morton of Philadelphia arguably ushered in the age of modern colorectal surgery by performing the first appendicectomy for appendicitis [1]. He was probably not aware that 400 miles away another significant, though malign, milestone in history had taken place six years earlier. In 1881 James Duke and James Bonsack of Raleigh, North Carolina created the world’s first cigarette-rolling machine. Their machine rolled 120,000 cigarettes per day thus revolutionizing tobacco smoking as a habit.
According to the WHO report on the global tobacco epidemic (2013), tobacco kills approximately 6 million people worldwide and causes more than half a trillion dollars of economic damage each year. It is the leading global cause of preventable death and is predicted to kill 1 billion people this century. About 10 million adults smoke cigarettes in Great Britain, approximately 22% of adult men and 19% of adult women are smokers (www.ash.org.uk April 2014). Smoking caused 60,000 cases of cancer in 2010 and 43,000 cancer deaths in 2009 [2]. Approximately 1.6 million hospital admissions in 2012/13 among adults aged >35 were primarily smoking related [3]. According to the report by Surgeon General report in 2013, the annual cost for direct medical care of adults attributable to smoking between the years 2009 and 2012 was $132.5 to 175.9 billion. More than 2.3 billion people are now covered by at least one of the WHO Framework Convention on Tobacco Control (WHO FCTC) but this covers mostly high income countries. Although substantial progress has been made in the global tobacco use since the adoption of WHO FCTC 10 years ago, more work is needed in the low and middle income countries [4].
The medical profession appreciate these devastating statistics and the general ill effects of smoking, in particular lung cancer and cardiovascular disease, but there is paucity of data on the effects of smoking in patients with colorectal disease. The aim of this narrative is to present a general review of smoking and its effect on colorectal disease with special reference to contemporary colorectal surgery.

Table 1

Table 2

Smoking and Appendicitis

Appendicectomy is currently the commonest general surgical emergency operation. In 1999 Montgomery et al. [5] showed that maternal smoking and or patient smoking was positively associated with appendicectomy by the age of 26 years. The unadjusted odds ratio for appendicectomy associated with cigarette smoking was 2.34 (95% CI 1.52–3.59) [5]. A more recent study found associations between tobacco use and risks of perforation of an inflamed appendix [6]. Smoking therefore increases the incidence of appendicitis and also the likelihood of complications.

Smoking and Diverticular Disease

Smoking is a risk factor for the development of complicated diverticular disease at a young age (Table 1). Turunen et al. [7] reported on 261 patients undergoing sigmoid colectomy for complicated diverticulitis. Smokers were younger, had more evidence of strictures, histological perforations and more episodes of diverticulitis following surgery. A smaller study comparing complicated diverticular disease and asymptomatic diverticular disease showed a greater proportion of smokers in the former group. Regression modelling demonstrated smoking to be an independent risk factor predisposing to postoperative complications [8].
Hjern et al. [9] concluded that in women, smoking appears to increase the risk of symptomatic diverticular disease even after controlling for confounding factors such as age, diabetes and obesity. Of particular note smokers had almost double the risk of perforation or abscess formation. Why smoking should be associated with increased complicated disease in women is uncertain, but it is known that smoking increases VIP (vasointestinal polypeptide) levels in the colonic mucosa [10], thus increasing colonic motility and intraluminal pressure [11], while impairing blood supply [12,13]. A contradictory study including only male health professionals concluded that smoking was not a substantial risk for symptomatic diverticular disease although less than 10% of the study population smoked (RR 1.25, 95%CI 0.75-2.09) [14].

Smoking, Colorectal Cancer and Colorectal Cancer Treatments

The International Association for Research on Cancer added Colorectal cancer to the list of smoking attributable cancers in 2009 [15,16]. The US Surgeon General did the same in 2014 [17]. According to several recent meta-analyses, the relationship between smoking and colorectal cancer incidence is likely dose dependent [18- 21]. The association seems strongest for three correlated molecular phenotypes of the disease: microsatellite instability (MSI) [22- 25], CpG island methylator phenotype (CIMP) [26-28] and BRAF mutation positive [25-27].
The association between colorectal polyps, cancer and smoking habits has been extensively studied (Table 2). The Cancer Prevention Study II was a large prospective cohort established by the American Cancer Society in 1982. Smokers of 20 or more years experienced higher colorectal cancer death rates, even when adjusted for multiple potential confounders. Consistent with a causal relationship with smoking, risk was higher in current than in former smokers and increased with smoking duration, number of cigarettes smoked per day, and pack-years. Among former smokers, risk decreased with the number of years since smoking cessation [29]. The association between smoking and increased all causes mortality and disease specific mortality is especially pronounced in colorectal cancer with micro satellite instability (MSI). Across sex, tumour site, stage, and MSI status, and for both all-cause and CRC-specific mortality, an increased mortality was found in patients who were smokers than in former smokers and highest in patients with a >40 pack-year history [30].
Using the cohort of patients who participated in the Cancer and Leukaemia group B phase 3 trials, a spin off study evaluated the impact of smoking on colon cancer recurrence and survival. Surgically treatable stage III colon cancer patients with no evidence of distant spread were included. Smoking status or time since smoking cessation did not impact on the disease-free survival, overall survival or recurrence-free survival, but a dose-response association was noted for smoking intensity, particularly for the risk of death or recurrence in higher quartiles of pack-years smoked before age 30 years when compared with non-smokers [31].
Yang et al. [32] have recently shown that in colorectal cancer survivors smoking is associated with a nearly two-fold higher risk of death compared with never smoking. These studies indicate that cigarette smoking is associated with higher all-cause and colorectal cancer–specific mortality in non-metastatic colorectal cancer.
In treatment of metastatic colorectal cancer with Cetuximab, current smoking was found to be associated with poorer response, quicker time to progression and decreased overall survival. There was no dose relationship among current smokers [33]. In another study observing survival among patients with a potentially curative colorectal resection and referred for consideration for adjuvant chemotherapy/radiotherapy, smoking was found to significantly lower cause-specific survival by around 20% at 5 years [34].
There is little data on the effect of smoking on outcomes after radiotherapy for rectal cancer in smokers versus non-smokers, but there is compelling evidence from other diseases. In head and neck cancer patients having radiotherapy active smokers had significantly more complications and significantly poorer 5 years overall survival, locoregional control and disease free survival [35]. Prostate cancer patients who were current smokers had a 40% relative increase of cancer relapse and were twice as susceptible to disease spread and death due to prostate cancer compared to non-smokers [36].

Smoking and Anal Cancer

Risk factors for anal cancer include HPV infection, multiple sexual partners and ano-receptive intercourse. Smoking, as a risk factor is less well known (Table 3). In a retrospective review of about 300 patients with anal cancer, current smokers were at higher risk for anal cancer, independent of age and other risk factors [37]. Two studies using standard chemoradiotherapy found that smoking adversely affected local disease control, however this did not affect disease specific survival and colostomy free survival [38,39]. The European Society of Medical Oncology Clinical practice guidelines state that smoking may worsen acute toxicity during treatment and lead to a poorer disease free and colostomy free survival. Every effort should be made to ensure patients stop smoking before therapy [40].

Table 3

Table 4

Smoking and Inflammatory Bowel Disease

There is a dichotomy in the relationship between smoking, ulcerative colitis and Crohn’s disease (Table 4). The British Cohort Study in the 1980’s concluded that smoking protects against Ulcerative Colitis (UC). The risk of developing UC is decreased in current smokers compared with lifetime non-smokers (OR 0.41 95%CI 0.34– 0.48). In contrast smoking increased the risk of developing Crohn’s Disease (CD) (OR 2.0 95%CI 1.65–2.47) [41].
In a meta-analysis of 16 studies that included 2962 patients, there was almost twice the rate of clinical relapse of CD, following surgery among smokers. The risk of re-operation was also twice as high at 10-year follow up. There was no significant difference in reoperation rate or postoperative acute relapses between ex-smokers and non-smokers, indicating that smoking cessation reduces clinical and surgical recurrence rates [42]. A more recent review article also suggests an increased risk of clinical recurrence rates among smokers with CD [43]. In smaller studies, where risk factors for re-do surgery for CD were analysed, smoking was found to increase the risk of redo [44] and secondary ileocolic resection [45].
Smoking has also been shown to increase the risk of endoscopic recurrence, with macroscopic lesions found in the neo-terminal ileum of 70% of smokers 1 year after surgery compared with 35% of non smokers and 27% of ex-smokers [46]. Endoscopic recurrence rates appear similar for ex-smokers and non smokers [47-49]. After ileorectal anastomoses for CD smoking was an independent risk factor which predicted further intervention and proctectomy [50]. In recent studies involving Ileal Pouch Anal Anastomosis (IPAA) patients, active smoking was a risk factor associated with development of CD in patients who underwent this procedure for indeterminate colitis [51]. Smoking was also found to be associated with pouch related hospitalization and pouch failure [52].
In a large retrospective cohort study of 3000 patients, evaluating the effect of smoking on current medical treatment (immunosuppressant’s and anti-TNF drugs) for CD, smokers were found to have a significantly decreased survival free of structuring disease, perianal complications and had a higher risk for requiring thiopurine therapy. Moreover, smokers were more frequently treated with steroids, immunosuppressants and anti-TNF drugs [53]. These results suggest that, despite the widespread use of immunosuppressant’s and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course with increased therapeutic requirements. In a smaller study of about 300 patients with CD, there was no statistically significant difference between smokers (current and ex) and non-smokers in relation to disease characteristics or post-operative complications. The smokers, however had a lower Cleveland Quality of Life score [54]. In a more recent study from Sydney IBD Database Cohort comprising about 1200 patients, smoking in CD was associated with increased proportional surgery rate (45.8% vs. 37.8%, P = 0.045), requirement for IBD-related hospitalisation (P = 0.009) and incidence of peripheral arthritis (29.8% vs. 22.0%, P = 0.027). Current smokers with UC demonstrated reduced corticosteroid utilisation (24.1% vs. 37.5%, P = 0.045), yet no statistically significant reduction in the rates of colectomy (3.4% vs. 6.6%, P = 0.34) or hospital admission (P = 0.25) relative to nonsmokers. Ex-smokers with UC required proportionately greater immunosuppressive (36.2% vs. 26.3%, P = 0.041) and corticosteroid (43.7% vs. 34.5%, P = 0.078) therapies compared with current and never smokers [55].

Smoking and Perianal Disease

In an epidemiological study of US veterans (74 with anal abscess or fistula and 816 without) recent smoking was found to be a risk factor for anal abscess/fistula development [56] (Table 5). Current smokers developed more perianal disease than smokers who quit less than a year ago. Increased OR 1.72 (95% CI 1.03–2.86, p=0.0375) was also observed when comparing current smokers and smokers who quit within the past 5 years compared with non-smokers. An accompanying editorial questioned our understanding of the origin of perianal sepsis and explores a plausible case for a causal relationship between smoking and perianal sepsis [57].
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disorder of hair follicles in apocrine gland-bearing sites. In a population based study of 200 patients, smokers (current and past) were found to have more severe HS compared to non-smokers (OR 2.0, 95% C.I 1.1–3.5) [58]. In a pair matched case-control study between patients presenting with HS and other dermatological conditions (atopic dermatitis, melanoma, varicose veins etc), the rate of active smokers was higher in the HS group (90% vs. 46%) [59]. The percentage of smokers among patients with HS was found to be higher in the above German and Polish study (73%) [60] compared to the national average (27% and 23% respectively).

Table 5

Figure 1

Figure 2

Smoking and Wound Healing

Smoking causes changes in all three phases of wound healing. Smoking enhances the initial haemostatic phase through elevated levels of circulating fibronectin; it reduces blood flow, aerobic metabolism and tissue oxygenation. It impairs the inflammatory phase with reduced neutrophil phagocytosis and abnormal monocytemacrophage responses whilst the proliferative phase is deranged with reductions in fibroblast function, epithelial regeneration and collagen metabolism. These events are manifested clinically as delayed healing, wound infection and necrosis [61-67] with subsequent anastomotic breakdown or herniation [68].
In a systematic review of 177 articles, smoking cessation was seen to reverse certain adverse factors on wound healing. Cessation restores tissue oxygen levels rapidly and reduces oxidative stress. The number of circulating neutrophils and the negative impact on neutrophil and monocyte-macrophage function are normalized. In the healing wound, inflammatory cell infiltration increases and wound contraction is partially reversed. In contrast, smoking cessation does not appear to reverse epidermal regeneration, fibroblast proliferation, and collagen synthesis and deposition, indicating that in the wound the detrimental effect of smoking on proliferation and remodeling is prolonged [69]. The pathophysiological effects of both smoking and smoking cessation are summarized in Figure1 and 2.
In a post hoc analysis of data from PROXI trial, including 1386 patients (emergency and elective laparotomy for surgical and gynaecological causes), smoking was found to be significantly associated with higher frequency of surgical site infections (SSI) (25% versus 17%, p value< 0.001) and burst abdomen (3.8% vs. 2.4%, p value 0.04) [70].

Cigarette Smoking and Outcomes after Colorectal Surgery

Smokers are more likely to suffer surgical, as well as, cardiovascular and respiratory complications [71,72]. Smokers are more likely to be admitted to an intensive care unit [73], have longer lengths of stay and higher mortality.
Two large retrospective studies from the Veterans Associations Surgical Quality Improvement Programme (VA SQIP) showed that smoking was associated with more post-operative complications following both general and cancer related surgical procedures [74,75]. In a further large study of patients undergoing curative resection for colorectal cancer, smoking (as a preoperative risk factor) was associated with more post-operative complications poorer overall survival and systemic recurrence [76] (Table 6).
In a more recent retrospective database (VA SQIP) study of almost 48,000 patients undergoing colorectal surgery for cancer, diverticular disease or IBD; current smokers were at a significantly increased risk of post-operative morbidity and mortality [77]. In a small study involving 38 patients, non-healing perineal wounds after abdominoperineal resection were observed in 26%. On principal component analysis of seven other factors, smoking was found to contribute 13.8% of delayed wound healing [78].
In another small, but well conducted randomised clinical trial, where an experimental wound was made and followed up, between non-smokers and smokers, wound infection was commoner among smokers (12% vs. 2%, p< 0.05). After four weeks of abstinence the wound infection levels were similar to never smokers [79]. In a retrospective case matched study of patients who developed acute fascial wound dehiscence requiring return to theatre following an earlier laparotomy, incidence of smoking was more common (46%) compared to those who did not develop the complication (16%, p=0.0002) [80].
In two large retrospective studies of over 3000 cases undergoing ventral hernia repair [81] and abdominal wall reconstruction [82], smoking was the only modifiable risk factor associated with wound infection and major operative complication. Current smoking was approximately 1.5 times more prevalent in subjects with postoperative wound infections. In 2010, the Ventral Hernia Working Group actively recommended smoking cessation as part of patient optimisation prior to elective surgery [83].
Transanal advancement flap repair (TAFR) has been advocated as a possible treatment of choice for trans-sphincteric fistula in ano. Initially promising reports [84-87] have been followed by less favourable results [88,89]. To examine this further 105 patients with crypto glandular perianal fistulae underwent TAFR and were assessed for healing outcomes. TAFR was successful in 69% at a median of 14 months. The healing rate varied between 60% in smokers and 79% in non smokers with a significant correlation between number of cigarettes smoked per day and reduced healing [90]. The same group went on to show significantly decreased blood flow in the rectal mucosa among smokers prior to TAFR [13], mainly demonstrated at the apex of the flap. In another study smoking was again found to be a factor adversely affecting healing of advancement flaps and increased recurrence rates [91]. In a study evaluating “staged fibrin sealant (FS)” technique and TAFR for treatment of complex perianal fistulae, 100% of smokers in the FS group developed recurrent fistulae [92].

Table 6

Table 7

Smoking and Anastomotic Leaks

Anastomotic leakage is a very serious complication after colorectal surgery [93,94], leak rates vary between 1.5% and 16% being highest in low rectal anastomoses [95]. Anastomotic complications cause increased morbidity and mortality [96], poor long term outcomes and impaired functional results [97] (Table 7).
A combined clinical and histopathological study, correlating smoking, hypertension and anastomotic dehiscence, among 147 patients, found a positive correlation between microvascular disease and anastomotic dehiscence, with an increased incidence among smokers [12]. In a retrospective analysis of 215 patients who underwent low anterior resections for rectal cancer multivariate analysis revealed the presence of a protective stoma and history of heavy smoking to be significantly and independently associated with anastomotic complications [98]. Similar studies of patients undergoing colonic or rectal resections used regression analyses to identify smoking, metastatic disease and alcohol abuse to be significantly associated with higher anastomotic leak rates [99,100]. A recent systematic review showed smoking to be an important adjustable risk factor for anastomotic leak [101]. It is also reasonable to hypothesise that there might be a cumulative effect of smoking and radiotherapy in particular on anastomotic healing [101]. A more recent clinical study of 246 patients undergoing left sided colonic resections, the percentage of anastomotic leak requiring an intervention, was significantly higher among smokers (17%) compared to non-smokers (5%) [102]. A much larger multicentre study from Germany including almost 18,000 patients over a 10 year period, also found smoking (reliant on patient history) to be an independent factor in both univariate (leak rate of 17% vs. 11%, p value >0.001) and multivariate analysis (O.R 1.332, 95% C.I 1.106 – 1.604) [103].

Conclusion

Cigarette smoking adversely affects the natural history of common colorectal conditions, their treatment and surgical outcomes. As well as the deleterious cardiorespiratory effects on blood supply, pulmonary function and tissue oxygenation there is also a smoking related impairment of the inflammatory response and tissue repair. The latter, directly associated with impaired wound healing, an increased incidence of anastomotic leakage, hernia formation and flap failure. Smoking is associated with poorer cancer outcomes and increased complications after colorectal surgery. Smoking is also associated with poorer outcomes after radiotherapy.
Smoking history should be an integral part of the colorectal patient’s assessment. There is an obligation to explain the effects of smoking on the natural history of the disease and its treatment. Surgeons must advocate and facilitate smoking cessation in order to empower patients to alter the course of their disease for their benefit. Whilst aware of the health risks of smoking in general terms many patients don’t appreciate the specific risk to their colorectal disease or their proposed surgery or radiotherapy. Smoking cessation should become an integral part of enhanced recovery protocols which is not the case at present in the UK. The optimal duration of smoking cessation and success of smoking cessation programmes has been a subject of few studies. A systematic review and Meta analysis concludes that at least four weeks of abstinence from smoking reduces respiratory complications and abstinence of at least three to four weeks reduces wound healing complications [104]. Another systematic review and meta analysis of smoking cessation interventions among oncology patients (counselling, nicotine replacement therapy, buproprion and varenicline) concludes that interventions in the perioperative period had a pooled odds ratio of 2.31 (95% C.I 1.32 – 4.07), making this an important teachable moment [105].
If smoking cessation advice is unsuccessful then the appropriateness of proceeding with elective surgery in the face of active smoking should be reconsidered [106]. If proceeding with surgery, then alteration in surgical strategy with reconsideration of anastomoses or flaps needs to be undertaken, particularly if other risk factors are present.

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