Male sex and history of ischemic heart disease are major risk factors for anastomotic leakage after laparoscopic anterior resection in patients with rectal cancer

Anastomotic leakage (AL) is a complication that occurs in 1.2 to 19.0% of patients during anterior resection (AR) for rectal cancer [1‐11]. This complication can lead to serious conditions such as peritonitis and sepsis, repeated surgeries or percutaneous intervention with prolonged hospitalization, increased cost [4, 6‐9], and a worse oncological prognosis [12, 13]. The basic requirements for anastomotic healing are an appropriate blood supply, healthy bowel ends, and tension-free anastomosis [14]. Risk factors for AL after AR have been discussed since anastomosis was initially established. Reported risk factors during open surgery include surgical duration, amount of intraoperative hemorrhage, and amount of blood transfusion [15, 16].

The number of elderly patients with colon cancer has increased along with the aging of society. Elderly patients often have co-morbidities and age-related physiological problems that can lead to worse postoperative complications compared with younger patients [17]. Risk factors for colon surgery should be re-evaluated depending on changes in social situation.

Laparoscopic surgery for rectal cancer can eliminate blind areas in the narrow surgical field of the pelvis, and rectal surgery can now proceed in a magnified operative field, thus improving the quality of this procedure, although laparotomy has historically contributed to the treatment of diseases of the digestive system because it allows complete visualization of the pelvis [18, 19]. Despite recent progress in laparoscopic surgery and standardized surgical technique [1‐3, 20‐27], some patients still develop AL. Little is known about risk factors for AL after laparoscopic rectal surgery. The present study aimed to determine risk factors for AL based on patients’ characteristics, extent of tumor progression, and factors related to surgery.

The present study aimed to identify risk factors for AL after laparoscopic AR for rectal cancer. Several risk factors are reportedly associated with AL after open AR, but few studies have examined the frequency of AL after laparoscopic AR. Univariate and multivariate analyses uncovered male sex and a history of IHD as independent predictive factors for AL after laparoscopic AR. The risk of AL is 4.7-fold higher in patients with, than without IHD.

How a history of IHD affects AL is uncertain. Kruschewski et al. found that IHD is a risk factor for anastomotic leakage after open AR [30]. Intraoperative laser-Doppler flowmetry has shown that reduced blood flow at the rectal stump is associated with an increased risk of AL [31]. A basic study by Fawcett et al. histologically demonstrated a relationship between AL and serosal microvascular disease at anastomotic sites, indicating that defective microcirculation reduces blood flow and leads to poor wound healing [32]. Considering that IHD is associated with arteriosclerosis, our findings suggest that patients with a history of IHD already have intestinal microvascular disease, which disrupts circulation at anastomotic sites. This notion remains to be proven from a pathological perspective. However, understanding the mechanism of AL development might contribute to the discovery or development of drugs to prevent AL.

Univariate analysis revealed significantly higher preoperative serum creatinine values in patients with AL. Although significance was not reached in the multivariate analysis (p = 0.01), confounders might have excluded preoperative creatinine value as a risk factor. However, we believe that the preoperative creatinine level is important with respect to postoperative AL in patients with rectal cancer. Kidney dysfunction is a common risk factor for IHD and arteriosclerosis [33, 34], and elevated serum creatinine is likely to indirectly indicate degrees of mesenteric microcirculatory dysfunction. Additionally, deteriorating drug metabolism/excretion and tissue edema from a water-electrolyte imbalance associated with kidney dysfunction might result in poor wound healing, which in turn can lead to AL [35]. Other risk factors comprised the LAR surgical procedure and transanal drainage (both p = 0.06). One published article describes a lower location of anastomosis as a risk factor for leakage [36]. The male pelvis is generally narrower towards the anus than that of females, which renders LAR more technically difficult in general. However, LAR was not an independent risk factor in the present study. We constructed diverting ileostomies more often after LAR than HAR (16.9% vs. 0%, p = 0.036; data not shown), because LAR is a substantial risk factor for AL in males. The only risk factor for anastomotic leakage in the present study was IHD. Among lifestyle diseases such as hyperlipidemia, diabetes, hypertension, and smoking that are closely associated with IHD, only smoking has been shown to be a risk factor for anastomotic leakage [30, 37]. However, the present analyses did not select smoking or any other lifestyle diseases as risk factors for anastomotic leakage. Thus, we reduced anastomotic leakage in patients with a history of IHD by creating a stoma.

Criteria for where a transanal drain is placed are not defined at our institution and transanal drainage is applied at the discretion of the surgeon. Whether or not to attach a transanal drain is controversial. Transanal drains are simple to attach and detach, which relieves patients of the need for prolonged surgery, but bowel contents cannot be removed from the intestine. In contrast, loop ileostomy prevents anastomotic leakages from worsening. However, complications that can arise due to loop ileostomy placement include outlet obstruction and stoma detachment. In addition, surgical stoma closure under general anesthesia confers additional stress on patients. A meta-analysis has shown that transanal tube positioning helps to lower the postoperative incidence of AL, hence reducing the necessity for subsequent reoperation [38]. In contrast, the AL rate was significantly higher in 11 (61%) of the 18 patients who required transanal drainage in the present study. These results suggest that AL cannot be prevented in a population of patients only by postoperative rectal decompression. Conversely, this finding might indicate that surgeons empirically identified patients who were likely to have AL at baseline, which in turn might have led to the more frequent application of transanal drainage in the AL group. However, to conclude from these results that transanal drainage is ineffective seems somewhat risky. This is because among the 45 patients who had transanal drainage but no AL, some of them might be able to avoid AL with transanal drainage without the need for a diverting ileostomy.

Finally, more elderly individuals tend to develop colorectal cancer, reflecting the recent aging of the Japanese population. The number of elderly patients with colorectal cancer accompanied by serious comorbidities including IHD is likely to further increase in the future. Therefore, selection of the surgical LAR method with a temporary stoma or the Hartmann procedure should be carefully considered.

At a rate of 11.6%, AL remains a common and serious complication of curative surgery for rectal cancer. The present study determined that males with a history of IHD were at high risk of AL after AR. Thus, a temporary stoma or the Hartmann procedure should be considered. Uncovering the mechanism of AL in such patients might lead to the development of innovative drugs that could prevent AL and reduce the need to construct permanent stoma.