The role of perineal application of prophylactic negative-pressure wound therapy for prevention of wound-related complications after abdomino-perineal resection: a systematic review

Background Closed perineal wounds often fail to heal by primary intention after abdomino-perineal resection (APR) and are often complicated by surgical site infection (SSI) and/or wound dehiscence. Recent evidence showed encouraging results of prophylactic negative-pressure wound therapy (pNPWT) for prevention of wound-related complications in surgery. Our objective was to gather and discuss the early existing literature regarding the use of pNPWT to prevent wound-related complications on perineal wounds after APR. Methods Medline, Embase, and Web of Science were searched for original publications and congress abstracts reporting the use of pNPWT after APR on closed perineal wounds. Results Seven publications were included for analysis. Two publications reported significantly lower incidence of SSI in pNPWT patients than in controls with a risk reduction of about 25–30%. Two other publications described similar incidences of SSI between the two groups of patients but described SSI in pNPWT patients to be less severe. One study reported significantly lower incidence of wound dehiscence in pNPWT patients than in controls. Conclusion The largest non-randomized studies investigating the effect of pNPWT on the prevention of wound-related complications after APR showed encouraging results in terms of reduction of SSI and wound dehiscence that deserve further investigation and confirmation. Electronic supplementary material The online version of this article (10.1007/s00384-020-03732-6) contains supplementary material, which is available to authorized users.


Introduction
Abdomino-perineal resection (APR) of the rectum consists of the ablation of the terminal colon, the rectum, the internal and external sphincters, and the confection of a terminal colostomy, as initially described by Miles [1]. APR is usually indicated for advanced adenocarcinomas of the lower third of the rectum (within 5 cm from the anal verge) and for recurrent squamous cell carcinoma of the rectum or anal margin after chemo-radiotherapy. Improvements to the techniques include neoadjuvant radio-chemotherapy for stages T 3-4 and/or radiologically node-positive adenocarcinomas, synchronous abdominal and perineal approaches, total mesorectum excision (TME, as introduced by Heald [2]), and minimally invasive techniques avoiding laparotomy for the abdominal approach.
Recently, emergence of sphincter-sparing procedures, such as partial and total intersphincteric resections for adenocarcinomas < 1 cm from the internal sphincter but sparing the external sphincter allowed reducing the indication for APR in favor of anterior resection. However, APR is still performed for rectal adenocarcinomas extending to the external sphincter, for incontinent patients, and for recurrent squamous cell carcinoma. Further, wider resections, such as extralevator abdomino-perineal excision (ELAPE [3]) removing the totality of levator ani muscles from their origin associated or not to multivisceral resection, are sometimes required in case of infiltration of levator ani muscles or surrounding organs, although indication for ELAPE is still debatable.
APR results in wide perineal defects. Usually, levator ani muscles are reapproximated using absorbable stiches. If a gap remains, the subcutaneous fat in the ischiorectal space or a synthetic or biological mesh can be used to fill the empty space [4]. In some cases, reconstruction using flaps, such as pedicled vertical rectus abdominis myocutaneous flap, local V-to-Y advancement flap (inferior gluteal artery perforator flap), and pedicled gracilis muscle flaps, is required [5,6].
However, perineal wounds often fail to heal, notably due to preoperative radiotherapy side effects [7,8], resulting in significant morbidity for patients, prolonged hospitalization, and increased costs for the healthcare system [9]. After failure to heal, a conventional negative-pressure wound therapy (NPWT) device (usually V.A.C .) is usually put in place to help healing by secondary intention.
Recently, NPWT preventively applied on closed wounds, also named prophylactic NPWT (pNPWT) or incisional NPWT (iNPWT), was reported to lower the risk of SSI after surgery in various surgical specialties, notably in gastrointestinal surgery [10][11][12]. Of interest, early publications reported encouraging results after APR, for which surgical wounds are more at risk of complications, but pooled evidence is lacking in that context.
The primary objective of the present systematic review was to gather and discuss the early existing literature regarding the use of pNPWT to prevent wound-related complications, notably SSI, on perineal wounds after APR.

Methods
This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [13] (Table S1). MEDLINE, Embase, and Web of Science were searched from inception to 8 November 2019 for original studies written in English, Swedish, or French including patients who benefited from perineal application of pNPWT after APR. Search strategy is summarized in Table 1. Case series and conference abstracts were considered. Additional records were identified by manual search of the reference lists of the included publications. Secondary analyses of previously published papers and studies including patients < 18 years old were excluded. Studies were screened for inclusion by two authors (ER, JM). Discrepancies were solved by a third author (NCB). The systematic review and meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO).

Perineal wound complications
Wiegering et al. reported one wound dehiscence (16.7% of patients) occurring after 8 days and requiring V.A.C. therapy for secondary healing [17].
Chadi et al. compared 27 patients with pNPWT with 32 patients with conventional wound dressing and found pNPWT          patients to have significantly less SSI than control patients (14.8% versus 40.6%, p = 0.04). The incidence of intraabdominal abscess (7.4% versus 3.1%, p = 0.59) or of emergency department visit (0% versus 6.2%, p = 0.18) did not differ between the two groups [14]. Chung et al. also reported significantly lower incidence of SSI among patients with pNPWT than in controls (9.1% versus 41.7%, p = 0.012) [20]. Rather et al., however, found similar incidence of SSI between patients with and without pNPWT (50% versus 64.3%) but described these infectious complications to be "less severe" in pNPWT patients. Noteworthy, 18.8% of pNPWT patients and 50% of control patients required V.A.C. therapy of the perineal wound for secondary healing. One patient who did not benefited from pNPWT required reoperation [19]. Van der Walk et al. reported similar incidences of SSI between pNPWT and control patients (70% versus 60%, p value not communicated). One patient from the conventional wound dressing group required reintervention [16]. Sumrien et al. reported significantly lower incidence of wound dehiscence in pNPWT patients than in controls (40% versus 9.4%, p = 0.01). Takahashi et al. observed a similar trend (0% versus 50%, p value not communicated) ( Table 5).

Discussion
In the present systematic review, we have included seven studies investigating the effect of pNPWT on the prevention of perineal wound complications after APR.
Two publications reported significantly lower incidence of SSI in pNPWT patients than in controls with a risk reduction of about 25-30% [14,20], therefore showing encouraging results in favor of perineal pNPWT. Two other publications described similar incidence of SSI between the two groups of patients but described SSI in pNPWT patients to be less severe [19], or the authors believed that pNPWT could accelerate wound healing [16]. Further, one study reported significantly lower incidence of wound dehiscence in pNPWT patients than in controls (40% versus 9.4%, p = 0.01) [15].
We note that these studies were pilot studies, which presented several limitations. These were heterogeneous in designs, patients' populations (with potential differences in terms of risk factors for wound-related complications), definition of controls (mainly historical), surgical procedures, pNPWT procedures (in terms of device, negative pressure applied, and duration of therapy-of note, several studies reported dysfunction of the device(s) requiring replacement and/ or discontinuation of therapy [15,16]), and reported outcomes (SSI, wound dehiscence, intra-abdominal abscess, emergency department visit, negative-pressure therapy for secondary healing, reoperation) and had small sample sizes, which constitute important limitations to their interpretation and prevent any meta-analysis of the actual literature in the field. However, we note that studies reporting a significant effect of pNPWT on the prevention of SSI and/or wound dehiscence were the studies with the largest sample sizes. Therefore, it might be likely that the absence of a significant effect observed in smaller studies might result from a type II error (lack of statistical power).
We believe that prevention of wound-related complications after APR is of crucial importance. For instance, these complications might increase length of stay with the subsequent risks of thrombo-embolic complications and nosocomial infections in these vulnerable patients and might also postpone administration of adjuvant therapy. We think that perineal application of pNPWT for the prevention of wound-related complications after ARP deserves further investigation, for example, with a large-enough randomized controlled trial, as the existing high incidence of perineal wound complications might allow to obtain important benefits even with a small effect of that therapy.

Conclusion
The largest non-randomized studies investigating the effect of pNPWT on the prevention of wound-related complications after APR show encouraging results in terms of reduction of SSI and wound dehiscence that deserve further investigation and confirmation.
Funding Open access funding provided by University of Geneva.

Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
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