Predictive risk factors for anastomotic leakage after anterior resection of rectal cancer in elderly patients over 80 years old: an analysis of 288 consecutive patients

With decreases in fertility and mortality rates, the problem of population aging is becoming increasingly severe [1]. The risk of colorectal cancer increases exponentially with age. According to the Globocan 2012 database of the World Cancer Research Center, it is estimated that the incidence of colorectal cancer in those over 75 years old in China is approximately 78,200 every year, accounting for 18% of the global incidence of colorectal cancer [2].

Anastomotic leakage (AL) is a common complication after anterior resection for rectal cancer. It not only significantly increases local recurrence rates and reduces long-term survival rates but also extends the length of hospitalization and wastes unnecessary medical resources [3‐7]. Patients with AL tend to suffer severe consequences, including peritonitis, widespread inflammation, organ failure, and septic shock. Elderly colorectal cancer patients with poor physical health, including diabetes, hypertension, coronary heart disease (CHD), and other comorbidities, as well as younger patients without these comorbidities, may not be able to cope with the physiological insult when AL occurs. A large number of studies have confirmed that gender, location of the anastomotic site, sarcopenia, preoperative albumin level, and other factors are closely related to the occurrence of AL. These factors can be used as predictive indicators of AL; however, most of them are targeted at young patients [5, 6, 8‐10]. Few studies have been conducted regarding whether the traditional predictors of AL can also be applied to elderly patients undergoing anterior resection (AR) or low anterior resection (LAR) for rectal cancer. Therefore, we conducted a single-center retrospective study with a large sample size to identify the risk factors for AL in elderly patients (age ≥ 80) with rectal cancer.

From January 2007 to May 2019, a total of 6185 consecutive rectal cancer patients underwent AR or LAR at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. The inclusion criteria were as follows: (1) patients aged 80 or older, (2) patients with tumors less than 15 cm from the anus and pathologically confirmed as adenocarcinoma, and (3) patients who underwent open or laparoscopic AR and LAR. The exclusion criteria were as follows: (1) patients with distant metastases or extensive abdominal implantation; (2) patients who underwent emergency surgery for reasons such as intestinal obstruction, bleeding, or perforation; and (3) patients with synchronous primary tumors. Finally, 288 patients met the criteria and entered this study.

In the present study, AL was defined as damage to the integrity of the intestinal wall of the anastomotic site caused by necrosis or abscess formation, resulting in communication between the intraluminal and extraluminal compartments of the abdomen according to the definition of AL proposed by the International Study Group of Rectal Cancer (ISREC) in 2010 [11]. AL was classified into three grades: grade A—only radiological evidence of a leak, without any treatment required; grade B—a symptomatic leak that requires either antibiotics or a percutaneous drain; and grade C—a symptomatic anastomotic leak that requires return to theater and a laparotomy. AL was diagnosed by meeting the criteria for grade B or C in the present study. Pelvic drainage tubes were routinely placed in all patients, and the pelvic drain was removed when the output of the drain was clear and lower than 50 mL/24 h. Patients with delayed AL more than 1 month after surgery were excluded from this study.

We defined elderly patients as being 80 years old or older. All procedures were performed by colorectal surgeons with more than 20 years of surgical experience, and all enrolled patients underwent radical surgery in accordance with the total mesorectal excision (TME) principle. The American Joint Committee on Cancer (AJCC, the seventh edition) staging system was used for tumor staging. All patients received a preoperative assessment, including physical and laboratory examinations, colonoscopy with biopsy, abdominal computed tomography scan, and pelvic magnetic resonance imaging. The guidelines of the National Comprehensive Cancer Network were used for perioperative management. Patients with T3, T4, or N+ middle or low rectal cancer received neoadjuvant chemoradiotherapy followed by surgery 6 weeks later. All patients received the same perioperative treatment regimen and routinely underwent bowel preparation and received prophylactic antibiotics for 1 day. Written informed consent was obtained from each patient included in the study. The ethics committee of the Cancer Hospital, Chinese Academy of Medical Sciences, approved this retrospective study (NCC 2017-YZ-026, Oct 17, 2017).

AL remains one of the most dreaded complications after anterior resection for rectal cancer, with an incidence rate of approximately 10% reported in the literature [5, 6, 9, 10, 12‐19]. This estimate includes asymptomatic anastomotic leakage, with an incidence as high as 50% [20]. In recent years, a large number of studies have reported risk factors associated with AL [5, 6, 9, 8‐10]. Often, clinical characteristics such as gender, BMI, ASA, or sarcopenia have been assumed to be major contributors to the development of AL. With population aging, the incidence of rectal cancer in elderly patients shows an increasing trend. However, few relevant studies have confirmed whether elderly patients (age ≥ 80) with colorectal cancer have the same risk factors for anastomotic leakage as conventional patients with colorectal cancer. The purpose of the present study was to identify the risk factors associated with AL in elderly patients (age ≥ 80).

The use of more than two cutting closures is bound to increase the inclination, resulting in a weak area where the cutting line overlaps, which will increase the risk of AL [16‐19]. Ito et al. [16] reported that the proportion of patients with vertical rectal division requiring three or more staples is smaller than that with transverse division (15% vs. 45%, P = 0.03), and multivariable analysis revealed that both TME (OR = 5.3; 95% CI = 1.2–22.7, P = 0.02) and three or more stapler firings during rectal division are significant and independent risk factors for AL (OR = 4.6; 95% CI = 1.1–19.2, P = 0.03). In 2009, Kim et al. [17] conducted a prospective study including 270 patients and reported that the application of multiple staples and anastomotic levels are major contributors to the development of AL. Park et al. [18] also provided strong evidence that the number of linear stapler firings > 3 increased the risk of AL after laparoscopic surgery for rectal cancer in 2013 (OR = 7.849; 95% CI = 3.776–16.314, P < 0.001). In our study, there were 111 (38.5%) patients with three or more staples for anastomosis; among them, 18 had AL and 93 had no AL. Univariate analysis showed that the number of stapler firings ≥ 3 was significantly different between the two groups (60.0% vs. 36.0%, P = 0.011). Multivariate logistic regression analysis showed that the number of stapler firings ≥ 3 was an independent risk factor for AL (OR = 4.77, 95% CI = 1.33–15.21, P = 0.035). These results are consistent with the results mentioned above. The increased use of stapler firings is often associated with some unfavorable conditions, such as low rectal cancer in obese male patients, patients with vascular disease after radiotherapy, or patients with previous multiple abdominopelvic operations.

Elderly patients have more comorbidities than young patients do. Multivariate logistic regression analysis in the present study showed that CHD was an independent risk factor for AL (OR = 8.33, 95% CI = 1.94–13.05, P = 0.003). How coronary heart disease affects the occurrence of AL has not been determined conclusively. A basic study by Fawcett found that the intestinal serosal microcirculation blood supply was an important factor for anastomotic healing [21]. Laser-Doppler flowmetry showed that the decrease in blood flow signal at the rectal stump was closely related to the occurrence of anastomotic leakage [22]. CHD is generally associated with systemic atherosclerosis that includes the blood vessels of the rectal stump [23], and the microcirculation blood supply condition of the rectal stump directly determines anastomotic healing. This notion remains to be investigated by a pathophysiological study. Furthermore, a prospective study including 276 rectal cancer patients conducted by Kruschewski et al. [24] showed that smokers had an increased risk of anastomotic leakage [OR = 6.42; 95% CI = 2.68–15.36], as did patients with coronary heart disease (OR = 7.79; 95% CI = 2.52–24.08). Our results were consistent with these findings.

A large number of studies have reported that the incidence of AL after anterior rectal resection was significantly increased by various factors, such as male sex, diabetes, and low tumor position. Our study similarly found that male sex (36.7% vs. 53.5%, P = 0.081) and diabetes (43.3% vs. 27.5%, P = 0.071) tended to be correlated with the occurrence of AL in elderly patients, which were comparable to those findings in young patients. Moreover, we also found that the number of stapler firings ≥ 3 and CHD were independent risk factors for AL in elderly patients (age ≥ 80) with rectal cancer. The limitations of this study include its retrospective nature and the relatively small patient sample size. In addition, the present study lacked an analysis of the effect of sarcopenia on AL after anterior resection of rectal cancer in the elderly. Multicenter large-scale prospective studies are worth pursuing to verify our results.

The number of stapler firings ≥ 3 and CHD were independent risk factors for AL in elderly patients (age ≥ 80) with rectal cancer. A temporary ileostomy or the Hartmann procedure is recommended for male patients and patients with CHD, obesity, or lower tumor location, which may increase the number of stapler firings used. Certainly, we recommend that the number of stapler firing should be minimized to alleviate the economic and physical burden of patients.