APR is widely used in the treatment of pelvic malignant tumors. A series of postoperative perineal wound complications is defined as nonhealing wounds, including delayed healing, excessive wound exudation, infection, abscess, hematoma and sinus secretion24,25. Nonhealing wounds not only delay recovery and extra hospitalization time but also lead to additional wound care and even secondary surgery, which would greatly ruin patients’ quality of life and endanger their health5,6,11,26. Similar to previous studies, we found that the occurrence of nonhealing perineal wounds after APR was 27.9%. In our study, the average hospital stay of the nHG was approximately 35 days, which is more than twice that of the HG. At the same time, the medical expense of nHG is 20% more than that of HG. Obviously, nonhealing wounds bring tremendous inconveniences and challenges to patients and their families12. There is no doubt that it will be helpful to reduce the occurrence of nonhealing wounds, improve the surgical outcome and unload the burden on families and society by formulating proper medical plans for each patient.
Therefore, there is an urgent need to seek proper and feasible approaches to reduce the occurrence of wound complications after APR. It may be helpful to decrease the occurrence of wound complications and assist in guiding perioperative management by assessing patients’ preoperative health status, evaluating potential risk factors, and even establishing a risk prediction model27. In this study, we first divided patients who underwent APR surgery into a healing group and a nonhealing group according to the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). The basic health information and surgical data of the two groups were compared and analyzed. Finally, we found that older age, hyperlipidemia and higher pathological Broders Grading might be potential risk factors for nonhealing wounds after APR.
Inevitably, the capability of tissues to renew and repair weakens with age in perineal wounds and other sites28–30. Jeschke and his group suggested that the probability of wound complications and the risk of death in burn patients increased linearly with age. Additionally, the wounds of elderly patients have the characteristics of slow healing and a severe degree, and even mild burns or impairment will lead to poor prognosis31. Consistent with these studies, we also found that the age of patients with nonhealing perineal wounds after APR was older. The mean age of the nHG was 70.6 years compared with 63.4 years in the HG (p = 0.011). The multifactor binary logistic regression analysis showed that age was one of the independent risk factors for perineal nonhealing wounds after APR. We think this age-related trend is associated with the following reasons. First, elderly individuals are more likely to suffer from malnutrition, and poor nutritional status is unable to provide energy and metabolites, which promote wound healing29,32−34. Second, studies have shown that local immune cells and the complement system are first activated when wounds appear35. Later, circulating immune cells are recruited to participate in the process of injury repair36. During this period, neovascularization also plays a role in transporting immune cells and substances37. The immune system is crucial for wound healing, while these normal and important processes gradually slow down with age, hindering wound healing in elderly individuals. Third, aging leads to a reduction in the migration, proliferation, differentiation and exosome secretion of mesenchymal stem cells, causing slow tissue remodeling and wound healing38–40.
In addition, our study suggested that hyperlipidemia might be an independent risk factor for nonhealing perineal wounds (p = 0.042). A study focused on postoperative complications in patients with colorectal cancer included 382 patients and reported that hyperlipidemia had adverse effects on delayed wound recovery and wound liquefaction in patients with rectal cancer41. Hyperlipidemia resulting in poor wound healing might be a consequence of local accumulation of cholesterol metabolic byproducts and blood microcirculation disturbance42–44, which make it difficult to maintain sufficient nutrient import for local wound healing. Additionally, elevated levels of low-density lipoprotein will lead to a significant inhibition of endothelial proliferation and cell cycle arrest, which is antiangiogenic and pernicious for wound healing. However, due to the small number of participants in this study, we are concerned that the relationship between hyperlipidemia and nonhealing wounds needs to be further explored to draw a more credible conclusion.
The relationship between pathological grading and wound complications after APR remains unidentified. Thorgersen and his fellows carried out a study of 540 patients and reported that a low tumor regression grade was identified as a significant risk factor for deep surgical site infection, which contributed to nonhealing wounds45. We also found a higher trend of Broders Grading in the nHG, which was a significant difference (p = 0.048) in our research. The pathological classification reflects the overall differentiation of tumors: the higher the grade is, the lower the degree of differentiation and the greater the malignancy of the tumor. We believe that a higher tumor stage might affect postoperative wound healing in the following ways. First, tumors of higher grade cause more serious invasion and damage to the blood supply of local normal tissue, which results in delayed wound healing. In addition, the resection range of the tumors of higher grading is relatively larger, leaving enlargement of the postoperative wound. It takes more time and risks for wound healing. Moreover, the overall conditions of patients with higher grading tumors are relatively worse and lack adequate nutritional status to support postoperative wound healing46.
The incidence rate of perineal wound complications after primary closure (PC) in APR is 30 ~ 66%4,14,21,47. Flap-based reconstruction has been widely used to reduce wound complications after APR. A series of studies have shown that flap-based reconstruction after APR could reduce the incidence of perineal wound complications compared with PC48–50. Rectus abdominis myocutaneous flap, omental flap, gluteal flap and anterolateral thigh flap are often used for perineal and pelvic reconstruction after APR, where GMF receives relatively less attention. However, previous studies suggest that there are several potential risks of applying these commonly used flaps; for example, rectus abdominis myo-cutaneous flaps are prone to leave donor site hernia and weaken abdominal strength18; omental flaps have the disadvantage of increasing the tumor recurrence rate51; anterolateral thigh flaps lack enough bulk to fill large perineal defects with dead space completely, increasing the risk of pelvic and abdominal infection52,53. As concluded by the American College of Colorectal Surgeons (ACCRS) and the Association of Coloproctology of Great Britain and Ireland (ACPGBI), the current evidence is insufficient to recommend which technique should be first utilized54,55.
In this study, we conducted gracilis-myofascial flap (GMF) reconstruction in 5 patients after APR, and gratifying results were achieved for both doctors and patients. In line with Mansher’s and Olivia’s studies, this suggests that the gracilis-based flap is an ideal material for pelvic floor reconstruction after APR10,56. During clinical application, we found that GMF has some unique advantages. Above all, GMF is a thigh-based flap that is located on the surface of the thigh and can be harvested without deep dissection. Thus, the utilization of GMF reduces the damage to the donor site. Second, GMF is a kind of axial flap, and its artery originates from the gracilis branch of the deep femoral artery. This means that an adequate blood supply could provide sufficient nutrition and energy for the survival of GMFs and later wound healing. Moreover, the gracilis muscle does not involve important vessels and anatomical structures at deep sites, and it does not undertake important movement functions of the lower limb. Therefore, there will be little trauma and minimal functional deficit for the thigh donor site after losing the gracilis muscle. Additionally, the amount of GMF tissue is so plentiful that it is enough to fill the pelvic floor defect without residual dead space, which can prevent abdominal and pelvic infection effectively.
Different from Mansher, Olivia and Chong, we adopted GMF instead of a simple gracilis flap10,20,23. The tissue of GMF is more abundant than simple gracilis muscle, and usually unilateral GMF could be enough for pelvic floor reconstruction. There are two important keys in the acquisition of GMF: flap design and the stripping of the vascular pedicle. The size of the GMF should be designed based on the result of accurate exploration of pelvic defects (need of recipient site) and the amount of thigh fat and muscle tissue (condition of donor site). The scope of subcutaneous dissection could be appropriately enlarged so that the flap could carry more tissue on the premise of direct suture of the donor incision. When obtaining the flap, we dissociated the gracilis muscle, deep fascia, adipose tissue and skin as a whole and then expanded the subcutaneous stripping scope by 1 ~ 2 cm compared with the skin incision. Finally, we removed the whole layer of skin to prevent leakage, dehiscence, necrosis and fever caused by glandular secretion of skin after flap transfer.
As a retrospective study, our study has some limitations. First, the overall number of patients was 86, while the number of patients who underwent pelvic floor reconstruction with GMF was relatively small. Therefore, although our patients with GMF reconstruction all showed quite good surgical outcomes, the conclusion may still lack representativeness. In addition, there is a lack of comparative analysis among GMF and other flaps due to the limited use of other flaps in our center. Therefore, we plan to collect more data from patients with GMF reconstruction and further expand the number of cases in the next step.
In conclusion, this study found that old age, hyperlipidemia and high Broders Grading are risk factors for nonhealing wounds after APR. In addition, nonhealing perineal wounds after APR will prolong the hospitalization time and increase the medical cost. It will be of great help to combine these factors, analyze the risk of wound complications and provide a reference and reminder for surgeons. Gracilis-myofascial has a good effect on pelvic floor reconstruction and provides more means for the prevention and treatment of nonhealing perineal wounds.