Wound Closure After Port Implantation

A Randomized Controlled Trial Comparing Tissue Adhesive and Intracutaneous Suturing

Background: Wound healing after pectoral port implantation is a major factor determining the success or failure of the procedure. Infection and wound dehiscence can endanger the functionality of the port system and impede chemotherapy. The cosmetic result is important for patient satisfaction as well.

Methods: From August 2015 to July 2017, adult patients with an indication for port implantation were entered into a prospective, randomized and controlled single-center study. The skin incision was closed either with tissue adhesive or with an intracutaneous suture. The primary endpoints were the total score of the scar evaluated by the patient and the investigator on the POSAS scale (Patient and Observer Scar Assessment Scale: 6 [normal skin] to 60 points), blinded assessment of photographic documentation by ten evaluating physicians, and the patient’s reported quality of life. The calculation of case numbers was based only on the patients’ overall POSAS assessment, which was tested for non-inferiority. The secondary endpoints were other complications (infection, dehiscence) and the duration of wound closure (trial registration number NCT02551510).

Results: 156 patients (60  ± 13 years, 64% women) participated in the study. The patient-assessed total POSAS score of tissue adhesive revealed non-inferiority to suturing (adhesive 11.7  ± 5.8 vs. suture 10.1  ± 4.0, p for non-inferiority <0.001). Both the investigators in their POSAS assessments and the blinded physician evaluators in their assessment of photographically documented wounds rated wound closure by suturing better than closure with tissue adhesive. No significant differences were found between groups with respect to quality of life or the frequency of wound infection or dehiscence.

Conclusion: Closure of the upper cutaneous layer with tissue adhesive is a suitable and safe method of wound closure after port implantation.

In port implantation, skin suturing is a common standard procedure for wound closure (1). However, in the case of surgical incision wounds that are not under excessive tension, the use of tissue adhesive may be appropriate. Less foreign material, less trauma, and a bacteriostatic protective film would be beneficial especially for patients with sensitive skin and reduced immune defenses, in particular those on glucocorticoid therapy or chemotherapy. Wound dehiscence following port implantation may result in port pocket infection with associated functional limitations or, in the worst case, port sepsis (2). Following suture closure of the wound, waterproof film dressings are applied for the purposes of personal hygiene. This can be dispensed with in the case of wound closure using tissue adhesive.

Previous studies described the closure of skin wounds in the facial area with tissue adhesive as faster and less painful than with suturing—with comparable complication rates and cosmetic success (1, 3, 4). These promising results have also been confirmed in randomized studies in a variety of other surgical procedures and on different areas of the body (5, 6).

The aim of our study was to compare the success with which surgical wounds heal following port implantation depending on the type of wound closure, that is to say, whether the wound was closed with tissue adhesive or with intracutaneous suturing. Primarily, the assessment of wound healing by patients and evaluating physicians as well as the effect on quality of life were to be be compared.

Patients and methods

Study design

This randomized controlled monocentric study represents an investigator initiative study (IIS). Randomization at a ratio of 1:1 took place immediately prior to port implantation (computer-generated randomization list, Center for Clinical Studies, Jena University Hospital, Jena, Germany). Skin scars were to be assessed 2 months following wound closure—initially unblinded by the patients themselves and then by experienced investigators, independently of patients. In addition, an indirect, blinded assessment of photographic documentation was carried out by 10 independent physicians from a variety of surgical and interventional disciplines (Figure 1).

Figure 1

Flow diagram of the study

The study protocol was granted approval by the ethics committee of the Friedrich Schiller University Jena (No. 4165–07/14). All participants in the study gave their written informed consent to take part in the study, which was conducted in line with the guidelines on medical research according to the Declaration of Helsinki. The study was registered at ClinicalTrials.gov (NCT02551510).

Study population

Patient enrollment took place between August 2015 and July 2017. Patients aged from 18 years in whom a central venous primary port was indicated to create long-term access for chemotherapy and/or parenteral feeding or infusion treatment were deemed suitable. Patients at high risk of bleeding (thrombocytes ≤ 50/nL, aPTT ≤  20  s, one-stage prothrombin time ≤ 50%), systemic infection, local infection in the surgical area, or those with known allergy to materials used in the study were excluded.

Wound closure

Following skin disinfection, sterile draping, and local anesthesia, the radiologists implanted the port system under fluoroscopic guidance, according to standard medical specialist practice. The ultrasound-guided Seldinger technique with access via the internal jugular vein was used. This was followed by a subcuticular suture over the port system in both treatment groups with simple interrupted sutures of absorbable, antiseptic-coated suture material (Vicryl plus, USP 3–0, Ethicon). This enabled virtually tension-free adaptation of the wound edges to be achieved (7, 8).

In the control group, a continuous intracutaneous suture of absorbable synthetic suture material (Monocryl, USP 3–0, Ethicon) was placed. The wound edges were then fixed with wound closure strips and a dressing was applied. Patients had to wear a waterproof film dressing to shower.

In the intervention group, the wound was closed with a tissue adhesive (Histoacryl Flexible, B. Braun Melsungen) following the subcuticular suture. This tissue adhesive is made of n-butyl-2-cyanoacrylate with an added plasticizer. Following thorough hemostasis, a thin layer of the tissue adhesive was applied to the edges of the wound. It was important here to avoid penetration of the adhesive into the wound opening. The edges of the wound were then held together for 30 s. Cyanoacrylate immediately polymerizes upon contact with tissue and forms a strongly binding film. During the healing phase, brief contact with water during washing or showering was allowed in this group.

Endpoints

Primary endpoints included the total score of the scar as assessed by the patient and the investigator on the patient and observer scar assessment scale (POSAS, 9) at 2 months following wound closure. Another primary endpoint was a blinded assessment of photographic documentation by 10 evaluating physicians on a scale of 1 (normal skin) to 10. The specialists—comprising three plastic surgeons, three vascular surgeons, two radiologists, and two dermatologists—made independent assessments. The third primary endpoint was the effect of the type of wound closure on quality of life (EQ-5D-5L and EQ VAS). The POSAS assessment involved rating each of the six individual parameters pain, itching, color, stiffness, thickness, and surface area (as assessed by the patients), as well as vascularity, pigmentation, thickness, relief, suppleness, and expansion (as assessed by the investigators), on a scale of 1 (normal skin) to 10. Thus, the overall score could range between 6 and 60 points, with a higher score representing poorer scar quality.

Secondary endpoints included the duration of wound closure, periprocedural complications, and overall mortality.

Statistical analysis

We determined the number of participants in the study on the basis of a preliminary study with five patients in each treatment group. The difference in total POSAS score as assessed by the patients was 5.4 points (95% confidence interval for the difference: [4.0; 14.8]; tissue adhesive 19.2  ± 7.7, suture 13.8  ± 2.4; p = 0.03). Assuming α = 0.025 and β = 0.1, as well as a non-inferiority threshold for wound closure with tissue adhesive of 4 points in the patient-assessed group, yielded a required number of participants of 78 patients per group. The non-inferiority threshold resulted from the assumption in a previous study that a difference of ≥ 4 points in a single category should be considered as significant (10).

Continuous data were compared with the Mann-Whitney U test and categorical data with the chi-square test or Fisher’s exact test. The correlation between POSAS and the Q-5D-5L index was determined with Spearman’s correlation analysis. In a departure from the protocol, 10 rather than three blinded evaluating physicians took part in order to increase representativeness. The intraclass correlation coefficient (ICC, a model for two-way random effects, mean values, and absolute agreement) describes the agreement between their ratings (11). A post hoc subgroup analysis served to determine possible effects of belonging to a subgroup on patients’ total POSAS scores. The Bonferroni multiple α level is 0.006 for the primary endpoint on non-inferiority. The remaining p-values for the secondary endpoints, the subgroup analysis, and superiority merely represent descriptive parameters. The analyses were performed using SPSS Statistics 22.0 and XLSTAT (version 2015.6.01.24026).

Results

Study participants

A total of 156 consecutive patients with planned port implantation surgery were included in the study (mean age 60 ± 13 years, 64.3% women). As a result of aborted port implantation in one patient in the adhesive wound closure group due to subcutaneous hematoma, the skin wounds were closed using tissue adhesive in 77 patients and an intracutaneous suture in 78 patients. Scar follow-up took place at 60  ± 8 days. The primary endpoint could be assessed in 61 patients in each group (78.7%) (Figure 1).

Port implantation was due to breast cancer in 33.3% of patients, gastrointestinal cancer in 20.5%, and lung cancer in 15.4%. The indication for port implantation was chemotherapy in the majority of cases (93.5%). The comparison groups were balanced in terms of demographics, comorbidities, underlying diseases, medication, and indication for port implantation (Table 1, eTable).

Table 1

Procedural characteristics of port implantation according to type of wound closure

eTable

Wound closure following port placement: a randomized controlled trial comparing tissue adhesive and intracutaneous suturing

Primary endpoints: scar assessment and quality of life

Wound closure with adhesive was found to be non-inferior to closure with intracutaneous suturing in terms of patients’ overall assessment of the scar on the basis of the POSAS scale (score of 6, comparable to normal skin, to 60) at 2 months following port implantation (skin suture: 10.1  ± 4.0 versus tissue adhesive 11.7  ± 5.8, p = 0.08, mean difference 1.6, one-sided 97.5% confidence interval [– ∞; 3,4], p for non-inferiority < 0.001). Scar thickness was the only single criterion rated as worse by the patients after wound closure with adhesive than after suture closure (on a scale from 1 for normal skin to 10: skin suture 1.6 ± 0.7 versus tissue adhesive 2.0 ± 1.4, p = 0.04). Patients in both groups rated color changes to the scar more negatively than did the evaluating physicians (Figure 2a).

Figure 2

POSAS scale to assess wound healing at 2 months following wound closure by tissue adhesive or intracutaneous suturing

In the unblinded assessment by the investigators, wound closure with a suture scored higher compared to closure with tissue adhesive (total POSAS score as rated by investigators for suture closure: 10.2 ± 4.0 versus wound closure with tissue adhesive 12.8 ± 4.2, p < 0.001). In detail, the investigators deemed scars to be better in terms of thickness, relief, suppleness, and expansion following suture closure (Figure 2b).

Blinded assessment of photographic documentation of scars by 10 specialists confirmed the advantage of wound closure by suture (general impression on a scale from 1 for normal skin to 10: suture closure 2.9 ± 1.0 versus wound closure with tissue adhesive 3.3 ± 1.0, p < 0.005). Concordance between medical specialists in the assessment was good (ICC: 0.79; 95% confidence interval [0.65; 0.87]).

The type of wound closure did not affect the change in health-related quality of life reported by patients (EQ-5D-5L and EQ VAS) at 2 months following port placement (eFigure a and b). A weak correlation between own assessment of the scar and quality of life in the suture closure group was not significant (r_s  = −0.20 [−0.43; 0.05]). In the adhesive wound closure group, scar assessment and health-related quality of life were not correlated (rs = −0.03, [−0.28; 0.23]) (eFigure c).

eFigure

The effect of wound closure on health-related quality of life

Secondary endpoints and post-hoc analyses

Although the subcuticular suture took longer in the group undergoing wound closure with tissue adhesive (0.7 ± 1.5 min longer, p < 0.001), it was possible to close the upper cutaneous layer faster with adhesive (tissue adhesive 1.7 ± 0.8 min versus skin suture 6.6 ± 2.1 min, p < 0.001). At the same time, more simple interrupted sutures were placed in the subcuticular suture in patients in the adhesive wound closure group than in the suture closure group. Overall, the wounds in the tissue adhesive group were closed more quickly (4.2  ± 2.4  min less, p < 0.001). The scars of the wounds closed with tissue adhesive were on average longer than those treated with sutures (Table 1).

There was no difference between treatment groups in terms of the incidence of complications. Approximately one fifth of all patients developed a hematoma not requiring treatment in the port pocket (skin suture 21.5% versus tissue adhesive 19.7%, p = 0.26), and 6.2% of patients in the suture closure group developed a local allergic reaction (0% in the tissue adhesive wound closure group) (Table 2).

Table 2

Complications and mortality within the first 2 months (60 ± 8 days) following port implantation

Bloodstream infection occurred in 4.6% (three patients) in the suture closure group and in 1.5% (one patient) of patients in the adhesive wound closure group (p = 0.61). The port pocket became infected in two patients per group. Overall mortality at 2 months following port implantation was 12.9% (12.8% suture versus 13.0% tissue adhesive, p = 0.98). There was no association with port implantation.

The general impression made by the scar on patients and evaluating physicians on a scale of 1 (normal skin) to 10 was worse following wound closure with tissue adhesive compared to closure with suturing (Figure 2). There was no difference in the overall assessment as made by patients depending on the subgroups to which they belonged (Figure 3).

Figure 3

Subgroup analysis of the POSAS scar assessment by patients at 2 months following wound closure with tissue adhesive or suture

Discussion

This randomized controlled trial comparing wound healing after port placement on the basis of wound closure using tissue adhesive or intracutaneous suturing showed adhesive to be non-inferior from the patient’s perspective. The subjective overall impression made on patients by the scar was non-significantly worse following wound closure with tissue adhesive compared to suture wound closure. The evaluating physicians deemed the result to be worse following closure with tissue adhesive. The two methods did not differ in terms of quality of life and incidence of wound infection or dehiscence.

In the overall assessment made by patients, the difference between adhesive closure and suture closure was smaller compared to that from the investigators’ point of view. A contributing factor may have been the fact that pain and itching, which were the same following both types of closure, were assessed exclusively by the patients themselves. Finally, Chae et al. showed that not only cosmetic success but also symptoms, in particular itching, significantly impact the assessment (12). Likewise, the criterion “scar stiffness” could only be assessed by the patients themselves. This aspect was perceived to be more negative following suture closure than the determination of suppleness by the investigators. This may also have contributed to a smaller discrepancy between the methods. As described for burn injuries (10), the overall impression made on patients by the scar was worse compared to their total POSAS score. This could be explained by the fact that the assessment made by patients is more subjective than the sum of assessments of six specific parameters.

While a previous study identified the cosmetic outcome of wound closure as a predictor of patient satisfaction with port implantation overall (SF-12 questionnaire) (13), our study showed no association between patient scar assessment and type of wound closure or with health-related quality of life. This could be attributable to the negligibly small changes to quality of life in both treatment groups before and after port implantation, or to the broader definition of quality of life according to EQ-5D-5L. It is also possible that the earlier timing of the interview compared to 6 months in the earlier study plays a role.

In vitro experiments suggest an antimicrobial effect for cyanocacrylate-containing wound adhesive on Gram-positive bacteria (14, 15, 16). Furthermore, in the case of contaminated wounds, one must assume that suture channels and suture material are more likely to promote infection. Although (waterproof film) dressings increase the time required for wound care following suture closure, they are strongly recommended for protective purposes. Following wound closure with tissue adhesive, patients are able to attend to personal hygiene without dressings. This dispenses with the need for dressing changes, thereby reducing the time and cost required and increasing patient comfort.

In our study, as in previous studies (17), there was no difference either in the infection rate or in wound dehiscence when the specific follow-up recommendations were followed. The incidence of wound infection was overall comparable to previous studies on port implantation (2–4%) (17, 18).

The upper cutaneous layer could be closed faster with tissue adhesive than with intracutaneous suturing, as previously reported (1, 19). However, it is unlikely in the grand scheme of things that the time saving of a few minutes was relevant for the patient and the operator. This assessment is shared by a previous study on wound closure following breast lump excision (20). Added to this is the fact that, in order to reduce wound tension, more time was spent in our study on the subcuticular suture before applying the wound adhesive.

Limitations

The sample size calculation was based only on the total POSAS score as assessed by patients. This limits the statistical validity of the other endpoints. Since patient and observer blinding was not possible, an assessment bias cannot be ruled out. We used neither spectrophotometric examinations nor ultrasound examinations. When assessing scars on the basis of photographs, only a general impression could be gained.

Moreover, there is no minimum score defined for the POSAS scale that would describe a clinically relevant change for the patient. Thus, the non-inferiority threshold of 4 points is based merely on our own assessment, as well as on a categorization proposed by Spronk et al. (10).

A further limitation lies in the short follow-up period. One can assume that further changes to scar quality will occur even at 2 months. Whether and to what extent tissue adhesive closure and suture closure differ in this regard in the medium term remains unclear.

Summary

Tissue adhesive for wound closure is not inferior to skin suture closure according to patients’ assessment of the scar at 2 months following port implantation. No differences were found between the two methods with respect to the incidence of wound infection or wound dehiscence. Therefore, even though skin suturing was rated higher by the investigators, wound closure using tissue adhesive is a suitable and safe alternative to skin suturing. Other advantages include the fact that the procedure can be carried out quickly and no bandages or plasters are required.

Funding

This investigator-initiated study was made possible by the financial support of Aesculap AG, Tuttlingen, Germany. This clinical investigation is sponsored by the Friedrich Schiller University in Jena, Germany. Aesculap AG had no influence on the implementation, analysis, or publication of the study.

Authors’ declaration on the disclosure of primary data

Individual, anonymized patient data on which the results of the present article are based will be made available 3–36 months following publication to researchers submitting a methodologically sound analysis proposal. Proposals indicating the aim of the evaluation should be addressed to: [e-mail].

Conflict of interest statement
Prof. Teichgräber received consulting fees from Becton, Dickinson and Company. He received study support (third-party funding) from Aesculap AG.

The remaining authors declare that no conflict of interests exists.

Manuscript received on 13 February 2021, revised version accepted on 18 August 2021.

Translated from the original German by Christine Rye.

Corresponding author
Prof. Dr. med. Ulf Teichgräber
Institut für Diagnostische und Interventionelle Radiologie
Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena
Am Klinikum 1, 07747 Jena

Cite this as
Witting S, Ingwersen M, Lehmann T, Aschenbach R, Eckardt N, Zanow J, Fahrner R, Lotze S, Friedel R, Lenz M, Schmidt C, Miguel D, Ludriksone L, Teichgräber U: Wound closure after port implantation—a randomized controlled trial comparing tissue adhesive and intracutaneous suturing. Dtsch Arztebl Int 2021; 118: 749–55. DOI: 10.3238/arztebl.m2021.0324

►Supplementary material

eTable, eFigure: www.aerzteblatt-international.de/m2021.0324

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