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POLSKI PRZEGLĄD CHIRURGICZNY 2015, 87, 3, 124 128 10.1515/pjs-2015-0031 Influence of obesity on anastomotic leakage after anterior rectal resectionperformed due to cancer Jerzy Piecuch 1, Maciej Wiewióra 1, Monika Szrot 1, Janusz Jopek 1, Albert Krzak 2, Szymon Haza 2, Krystyn Sosada 1 Department of General and Bariatric Surgery and Emergency Medicine, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice 1 Kierownik: prof. dr hab. K. Sosada Student Scientific Society, Department of General and Bariatric Surgery and Emergency Medicine in Zabrze, Medical University of Silesia in Katowice 2 Opiekun Studenckiego Koła Naukowego: dr n. med. M. Wiewióra Anterior resection for rectal cancer carries the risk of serious complications, especially fistulas at the site of anastomosis. Numerous factors have been shown to impact anastomotic leakage. The results of studies on the influence of obesity on the frequency of anastomotic leakage after rectal resection performed due to cancer have been contradictory. The aim of the study was to evaluate the relationship between body mass index (BMI) and frequency of anastomotic leakage after anterior rectal resection performed due to cancer. Material and methods. This retrospective analysis included 222 subsequent patients who had undergone anterior resection due to cancer with an anastomosis formed with a mechanical suture. The patients were divided into 3 groups depending on their BMI quartile as follows: Group I, BMI < 23.8 kg/m 2 (lower quartile); group II, BMI between 23.8 and 29.38 kg/m 2 (middle quartile); and group III, BMI > 29.38 kg/m 2 (upper quartile). Results. Anastomotic leakage occurred in 8 (3.6%) patients. Fistulas occurred in 4 out of 61 patients (6.56%) in group I, which was the highest incidence of fistulas for all 3 groups. In group II, fistulas occurred in 2 out of 55 patients (3.63%), and similarly, in group III, they occurred in 2 out of 106 patients (1.87%). The differences found in the frequency of fistulas between groups were not statistically significant (p=0.31). The logistic regression analysis did not show any relationshipbetween leakage and age (p = 0.55; OR = 1.02; 95% CI: 0.95 1.1), sex (p = 0.97; OR = 0.97; 95% CI: 0.22 4.25) or BMI (p = 0.27; OR = 0.58; 95% CI: 0.22 1.53). Conclusions. The results of our study show that BMI did not have any influence on the frequency of anastomotic leakage after anterior rectal resection performed due to cancer. Key words: obesity, rectal cancer, anterior resection, anastomotic leakage Obesity is a risk factor for some cancers, including rectal cancer (1, 2). Rectal resection (3) is the typical treatment of choice in patients with rectal cancer. Rectum excision, regardless of the type of operation, creates a risk of serious complications. Postoperative complications have been reported in 30% of patients, and mortality after rectal resection ranges from 2.4% to 4% (4, 5, 6). Anastomotic leakage is one of the most common complications after anterior resection for rectal cancer (7). Many factors, including obesity, have been reported to influence the occurrence of anastomotic leakage (8, 9, 10). The aim of this study was to determine the influence of obesity on the frequency of anastomotic leakage after anterior rectal resection performed due to cancer. Material and methods This retrospective study included 222 consecutive patients who had undergone anterior rectal resection due to cancer. The general group characteristics are presented in tab. 1. The study group consisted of 127 (61.71%) men and 85 (38.29%) women, with a mean age of

Influence of obesity on anastomotic leakage after anterior rectal resectionperformed due to cancer 125 Table 1. General characteristics of patients after anterior resection for rectal cancer Pacjenci z rakiem odbytnicy / Patients with rectal cancer n=222 Age (years) 64,24 ± 10,09 Gender females males 85 (38,28%) 137 (61,72%) BMI (kg/m 2 ) 26,48 ± 3,99 AJCC I stage II stage III stage IV stage 41 (18,47%) 78 (35,13%) 52 (23,4%) 51 (23%) Co morbidities: arterial hypertension 81 (36,48%) diabetes mellitus 21 (9,46%) coronary heart disease 57 (25,67%) cerebral vascular event 2 (0,9%) chronic obstructive pulmonary 9 (4,05%) disease lower limb ischemia 20 (23,44%) BMI body mass index, AJCC American Joint Committee on Cancer 64.24 ± 10.09 years, and a mean BMI of 26.48 ± 3.99 kg/m 2.The patients were divided into 3 groups depending on their BMI quartile: group I, BMI < 23.8 kg/m 2 (lower quartile); group II, BMI between 23.8 and 29.38 kg/m 2 (middle quartile); and group III, BMI > 29.38 kg/m 2 (upper quartile). The patients were operated on due to rectal cancers of varying clinical stages classified using the of American Joint Committee on Cancer (AJCC) classification, which is based on the system of Tumor-Node-Metastasis (TNM) (10). There were 41 (18.47%), 78 (35.13%), 52 (23.4%) and 51 (23%) patients with stage I, II, III and IV rectal cancers, respectively. The patients underwent midline incision laparotomy. In all cases, the continuity of the alimentary duct was reconstructed by end-to-end anastomosis with mechanical sutures. No routine check-up imaging was performed to evaluate anastomosis imperviousness. Anastomotic leakage was found on the basis of clinical examination, laboratory tests, X-ray with contrast media and computed tomography of the abdominal cavity and pelvis minor. Statistical analysis Continuous variables are presented as the means and standard deviations. Quality variables are presented as total values and percentages. Continuous variables were compared by t-student s test. Quality variables were compared by the chi-square test, and when the expected number was lower than 5, an accurate bilateral Fisher s test was applied. The frequency of anastomotic leakage in each group was estimated by log-linear analysis. Based on the logical regression model, the influences of factors, such as age, sex, and BMI, on anastomotic leakage were evaluated. Differences were considered statistically significant with p<0.05. Results Anastomotic leakage occurred in 8 (3.6%) patients. No differences in the distribution of sex, age, BMI and accompanying diseases among patients with and without fistulas in the anastomosis were found (tab. 2). Fistulas Table 2. Comparison of the patients with fistula and without fistula in anastomosis after anterior resection for rectal cancer Patient without anastomotic leakage n=214 Patient with anastomotic leakage n=8 Age (years) 64,17 ± 10,24 66,25 ± 4,5 0,83 Gender females 82 (36,9%) 3 (37,5%) 0,64 males 132 (59,4%) 5 (62,5%) 0,597 BMI (kg/m 2 ) 26,41 ± 3,98 26,53 ± 4,54 0,428 Co-morbidities: arterial hypertension 79 (35,59%) 2 (25%) 0,47 diabetes mellitus 20 (9,01%) 1 (12,5%) 0,56 coronary heart disease 55 (24,77%) 2 (25%) 0,956 icerebral vascular event 2 (0,9%) - 0,93 pchronic obstructive pulmonary disease 9 (4,05%) - 0,72 lower limb ischemia 19 (8,56%) 1 (12,5%) 0,55 p

126 J. Piecuch et al. Table 3. Logistic regression analyses for age. sex and BMI as predictors of fistulas afteranterior resection for rectal cancer β OR 95% CI p Age 0,022 1,02 0,95 1,1 0,55 Gender -0,029 0,97 0,22 4,25 0,97 BMI -0,55 0,58 0,22 1,53 0,27 in the anastomosis occurred in 4 out of 61 patients (6.56%) in the lower quartile BMI group (< 23.8 kg/m 2 ), which was the highest incidence of fistulas for all 3 groups. In the second quartile BMI group (23.8 <BMI 29.38 kg/m 2 ), anastomotic leakage was found in 2 out of 55 patients (3.63%). Anastomotic leakage was the least frequent in the quartile III BMI group (BMI 29.38 kg/m 2 ), occurring in 2 out of 106 patients (1.87%) (fig. 1). No significant differences were found in the frequencies of anastomotic leakage between the groups with relation to BMI (p=0.31). Similar results were obtained by a comparison of anastomotic fistula frequency in relation to rectal tumor grade (p= 0.905) (fig. 2). Fistulas Fig. 1. Frequency of anastomotic leakage in relation to BMI Fig. 2. Frequency of anastomotic leakage in groups in relation to tumor grade according to AJCC classification occurred in 4.88%, 2.56%, 3.85%, and 3.92% of patients with grade I, II, III and IV tumors, respectively. The logistic regression analysis did not show any relationshipbetween age (p = 0.55; OR =1.02; 95% CI: 0.95 1.1), sex (p =0.97; OR = 0.97; 95% CI: 0.22 4.25) or BMI (p=0.27; OR = 0.58; 95% CI: 0.22 1.53) and frequency of anastomotic leakage. Discussion Large intestinal tumors, including rectal tumors, are one of the most common malignant tumors occurring in men and women in Poland (11). The basic method of treatment is anterior rectal resection, which is has the risk of complications, including anastomotic leakage (12, 16). Anastomotic leakage after rectal resection significantly influences the course of the postoperative period, extends hospitalization time and increases mortality of patients after intestinal resection (13-16). According to some reports, fistula frequency after rectal resection has a wide range of 2. 8-14.9% (13-16). In the present study, anastomotic leakage occurred in 3.5% of patients after anterior resection for rectal cancer. Fistulas occurred three times more often in the lower quartile BMI group (below 23.8 kg/m 2 ) in comparison with the obese group (BMI 29.8 kg/m 2 ) (III quartile), but this difference was not statistically significant. This could be because of the small number of fistulas and the small sample size of this study. The pathophysiology of anastomotic leakage is multifactorial, and it is difficult to determine individual factors that significantly increase the risk of anastomotic leakage. Several risk factors of anastomotic leakage, including obesity, have been reported in the literature (7, 17, 18). Our results confirm a slightly higher frequency of anastomotic leakage in men; however, this was not statistically significant. We also did not find relationships between fistula frequency in anastomosis and age, sex or BMI. Excessive body mass is a risk factor of large intestinal cancer, especially in men (1, 19, 20). This relationship can be explained mainly by metabolic syndrome occurrence, increased insulin resistance and coexisting hormonal

Influence of obesity on anastomotic leakage after anterior rectal resectionperformed due to cancer 127 changes in adipocytokines and additionally by a change in intestinal flora and increased bile excretion (2, 20, 21, 22). Therefore, overweight and obese patients are the majority of patients that are operated on due to large intestinal cancer. In our study, 64% of the patients operated on due to rectal cancer were obese. According to some authors, obesity increases the difficulty of operations by increasing the operative time, resulting in increased blood loss (23, 24). The results of studies on the influence of BMI on anastomotic leakage are contradictory. Some reports mention a correlation between obesity and an increased frequency of anastomotic leakage (14, 16, 25). Other authors indicate that obesity is related with increased mortality but not an increased number of postoperative complications, excluding infections (8, 9, 10). In our study, we did not find any relationship between obesity and frequency of anastomotic leakage after anterior resection for rectal cancer. Additionally, in our study, tumor grade, which is an important prognostic factor for 5-year survival after rectal resection (26), did not have any influence on anastomotic leakage frequency. These results are similar to those presented in other published studies (17, 27). Eriksen et al found that the T3 feature can be associated with an increased anastomotic leakage frequency (28). Conclusions The results of our study show that BMI did not have any influence on anastomotic leakage frequency after anterior resection for rectal cancer. references 1. Renehan AG, Tyson M, Egger M et al.: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371: 569-78. 2. Bardou, Marc, Alan N. Barkun et al.: Obesity and colorectal cancer. Gut 2013; 62: 933-47 3. Renehan AG, Egger M, Saunders MP et al.: Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ 2002; 324: 813. 4. Jones OM, John SK, Horseman N et al.: Low anastomotic leak rate after colorectal surgery: a single-centre study. Colorectal Dis 2007; 9: 740-44. 5. Påhlman L, Bohe M, Cedermark B et al.: The Swedish rectal cancer registry. Br J Surg 2007; 94: 1285-92. 6. Law WL, Choi HK, Lee YM et al.: The impact of postoperative complications on long-term outcomes following curative resection for colorectal cancer. Ann Surg Oncol 2007; 14: 2559-66. 7. Szczepkowski M, Banasiewicz T, Krokowicz P et al.: Polish Consensus Statement On The Protective Stoma. Pol Przegl Chir 2014; 86: 391-404. 8. Rullier E, Laurent C, Garrelon JL et al.: Risk factors for anastomotic leakage after resection of rectal cancer. Br J Surg 1998; 85: 355-58. 9. Bokey L, Chapuis PH, Dent OF: Impact of Obesity on Complications After Resection for Rectal Cancer. Colorectal Dis 2014; 6: 896-906. 10. Campbell PT, Newton CC, Dehal AN et al.: Impact of body mass index on survival after colorectal cancer diagnosis: the Cancer Prevention Study-II Nutrition Cohort. J Clin Oncol 2012; 30: 42-52. 11. Didkowska J, Wojciechowska U, Zatoński W: Nowotwory złośliwe w Polsce w 2011 roku. Centrum Onkologii Instytut, Warszawa 2013. 12. How P, Shihab O, Tekkis P et al.: A systematic review of cancer related patient outcomes after anterior resection and abdominoperineal excision for rectal cancer in the total mesorectal excision era. Surg Oncol 2011; e149-55. 13. Piecuch J, Wiewiora M, Jopek J et al.: Mortality and anastomotic leakage after anterior resection for rectal cancer. Hepatogastroenterology 2012; 59: 721-23. 14. Kruschewski M, Rieger H, Pohlen U et al.: Risk factors for clinical anastomotic leakage and postoperative mortality in elective surgery for rectal cancer. Int J Colorectal Dis 2007; 22: 919-27. 15. Ziegler MA1, Catto JA, Riggs TW et al.: Risk Factors for Anastomotic Leak and Mortality in Diabetic Patients Undergoing Colectomy. Arch Surg 2012; 147: 600-05. 16. Kang CY, Halabi WJ, Chaudhry OO et al.: Risk factors for anastomotic leakage after anterior resection for rectal cancer. JAMA Surg 2013; 148: 65-71. 17. Pommergaard HC, Gessler B, Burcharth J et al.: Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis. Colorectal Dis 2014; 16: 662-71. 18. Matthiessen P, Hallbook O, Andersson M i wsp.: Risk factors for anastomotic leakage after anterior

128 J. Piecuch et al. resection of the rectum. Colorectal Dis. 2004; 6: 462-69. 19. Giovannucci E, Ascherio A, Rimm EB et al.: Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med 1995; 1225: 327-34. 20. Frezza EE, Wachtel MS, Chiriva-Internati M: Influence of obesity on the risk of developing colon cancer. Gut 2006; 55: 285-91. 21. Roberts DL, Dive C, Renehan AG: Biological mechanisms linking obesity and cancer risk: new perspectives. Ann Rev Med 2010; 61: 301-16. 22. Wolin KY, Carson K, Colditz GA: Obesity and cancer. Oncologist 2010; 15: 556-65. 23. Ballian N, Yamane B, Leverson G et al.: Body mass index does not affect postoperative morbidity and oncologic outcomes of total mesorectal excision for rectal adenocarcinoma. Ann Surg Oncol 2010; 17: 1606-13. 24. Poulsen M, Ovesen H: Is laparoscopic colorectal cancer surgery in obese patients associated with an increased risk? Short-term results from a single center study of 425 patients. J Gastrointest Surg 2012; 16: 1554-58. 25. Konishi T, Watanabe T, Kishimoto J et al.: Risk factors for anastomotic leakage after surgery for colorectal cancer: results of prospective surveillance. J Am Coll Surg 2006; 202: 439-44. 26. O Connell JB, Maggard MA, Ko CY: Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 2004; 96: 1420-25. 27. 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. 28. Eriksen M, Wibe A, Norstein J et al.: Anastomotic leakage following routine mesorectal excision for rectal cancer in a national cohort of patients. Colorectal Dis 2005; 7: 51-57. Received: 3.02.2015 r. Adress correspondence: 41-800 Zabrze, ul. Skłodowskiej-Curie 10 e-mail: jerzy.piecuch@wp.pl