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ONLINE EXCLUSIVE

Retrospective Clinical Evaluation of Negative-Pressure Wound Therapy for Infection Prevention Following Malignant Pelvic Bone Tumor Resection Reconstruction

Cai, Tao MD; Zhang, Lei MD; Zhu, Kunpeng MD; Hu, Jianping MD; Zhan, Taichen MD; Liu, Liwei MD; Li, Cheng MD; Zhang, Chunlin MD

Author Information
Advances in Skin & Wound Care: January 2021 - Volume 34 - Issue 1 - p 1-6
doi: 10.1097/01.ASW.0000723280.71047.73
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Abstract

INTRODUCTION

Malignant pelvic bone tumors present a number of challenges to orthopedists in terms of local control because of their local extension, large size, and complex anatomy, which increase the difficulty of resection.1–3 In the Enneking classification of pelvic bone tumors, the pelvis is divided into four parts. Most of the iliac crest belongs to Enneking type I. Enneking type II tumors occur in the periacetabular area, and Enneking type III in the public area. The sacrum is Enneking type IV.3,4 For most patients, malignant pelvic bone tumors usually involve more than one part of the pelvis, necessitating different methods of reconstruction.

Perioperative complications, including intraoperative blood loss, venous thrombosis, abdominal incision hernia, hematoma, sciatic nerve irritation, infection, and skin problems cause substantial postoperative mortality and functional impairment.1,3,4 To date, all the surgical techniques used for reconstruction of the pelvic ring following tumor resection have high complication rates. Infection is the most common complication following any type of pelvic reconstruction.5

Negative-pressure wound therapy (NPWT) was first promoted by Chariker et al in 1989.5 Today, NPWT dressings are very adaptable and can be contoured to fit wounds of varying shapes, sizes, and locations, providing a more dynamic function that reduces infection and promotes early closure. As a result, NPWT has been widely adopted among surgical specialties for management of both acute and chronic wounds. This study investigated whether the application of NPWT after resection and reconstruction of pelvic bone tumors could prevent infection and complications and whether the local recurrence rate would change for patients after treatment with NPWT.

METHODS

The authors retrospectively reviewed their facility’s bone tumor database and identified 82 patients who underwent pelvic reconstruction for malignant pelvic bone tumors between January 2003 and January 2016. All patients provided written informed consent, and the study was approved by the Institutional Review Board of Tongji University (Shanghai, China) and was performed in accordance with the ethical standards prescribed by the Helsinki Declaration.

The inclusion criteria were as follows: (1) any patient who had a malignant pelvic tumor surgically removed with wide resection and clear margins and (2) any patient who underwent pelvic reconstruction. Those who were initially treated elsewhere or referred for the management of metastasis following treatment were excluded to maintain the homogeneity of the study population.

The participants’ surgical techniques were reviewed, and the estimated infection rate, duration of antibiotic administration, and length of inpatient stay were recorded. Every month for the first 6 months after the operation, patients had to have a radiograph and computed tomography (CT) examination of their pelvis and lungs. Patients then had these tests completed every 3 months until 1 year after the operation. Finally, if the patient was asymptomatic, these tests were conducted every year until 5 years had passed. To evaluate lower-limb function, the Musculoskeletal Tumour Society Score was recorded for all patients including six aspects: pain, function, emotional acceptance, gait, limitation of walking, and condition of external support. The score is between 0 and 5 for each item, and the scores are converted into a percentage.

Negative-Pressure Wound Therapy

These authors used vacuum-sealing drainage (VSD) as NPWT. Vacuum-sealing drainage is composed of foam, drainage tubes, and transparent vapor-transmitting polyurethane film and is the most common way to achieve constant negative pressure for NPWT. The indications for its use included: (1) the VSD materials could be used in the residual cavities after the resection of pelvic bone tumors, and (2) the VSD materials could be used on the surface of the wound during pelvic tumor resection. The contraindications included: (1) the VSD material should not be in direct contact with the prosthesis; (2) the VSD material should not be in direct contact with blood vessels, nerves, the peritoneum, organs, or anastomotic sites; (3) bleeding should be well controlled prior to application of the VSD materials; and (4) patients allergic to polyvinyl foam or polyurethane film should not undergo the VSD technique.

After the patient received a wide en-bloc resection with clear margins, the lesion cavities were washed with distilled water at a temperature of 42.5° C at least three times for 10 minutes each. Then, for the intervention patients in the VSD group, wound cavities were filled with polyvinyl foam and drainage tubes. The wound, including the adjacent skin and the drainage tubes, was covered by a transparent vapor-transmitting polyurethane film. When the drainage tubes were connected to an adjustable negative-pressure aspirator, the pressure was maintained at 400 to 600 kPa. Secondary operations were performed 5 to 7 days later, and the VSD materials were removed. Intervention patients were implanted with one to two pieces of VSD material based on the size of the cavity during the operations. For the remaining control patients, two negative-pressure drainage tubes were placed into the cavities after the resection of bone tumors. If no infection appeared 2 weeks after the stitches were removed and the patients did not have any symptoms of infection or skin problems during the follow-up, the wound was determined to be healing.

Reconstruction Methods

Different methods of reconstruction were conducted based on the patient’s Enneking type. Free fibula, combined with pedicle screws and titanium rods, were used to maintain the integrity and stability of the pelvic rings following Enneking types I and IV resection (Figure 1). If Enneking type II was involved, a three-dimensional printed hemipelvic prosthesis and total hip replacement were used for functional reconstruction (Figure 2).

Figure 1.
Figure 1.:
SAMPLE CASE 1A, The radiograph of a male patient (age 35 years) demonstrating a pelvic mass of 6 months’ duration. B, The picture shows the specimen of the tumor after resection. C, The authors resected the pelvic tumor completely and reconstructed the pelvis with free fibula. D, Several pieces of vacuum-sealing drainage material were put into the cavity after the operation. E and F, The wound and the radiograph of the pelvis after the resection and reconstruction of the bone tumor
Figure 2.
Figure 2.:
SAMPLE CASE 2A, Radiograph of a man with a large pelvic chondrosarcoma. His first operation was conducted 9 years later with the same pathologic diagnosis. B, The vacuum-sealing drainage (VSD) materials were put into the wound cavity during the operation. C, Radiograph of the patient after the operation. D, No residual tumor cells were observed after hematoxylin-eosin staining of the washing fluid (removed 7 days after the first operation). E and F, Hematoxylin-eosin staining of the suspicious part of the VSD material shows no residual tumor cells

Cell Culture

For the patients in the VSD group, when the second operations were conducted to remove the VSD materials, all the washing fluid of the wound cavities was collected and centrifuged at 1,000 rpm for 3 minutes. After that, the precipitate was treated with 2 mL trypsin and put into the incubator at 37° C under 5.0% CO2 in air for 1 minute, and then 6 mL fetal bovine serum (FBS) was used to neutralize the digestion of trypsin. After that, the mixture was centrifuged at 1,000 rpm for 3 minutes, and the precipitate was grown in plastic culture flasks with high-sugar Dulbecco modified eagle medium. Each medium was supplemented with 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. The flasks were kept in a humidified incubator at 37° C under 5.0% CO2. The supernatant was removed after 24 hours, and the plastic culture flasks were washed three times with phosphate-buffered saline to remove impurities from the supernatant. After that, the flasks were kept in the incubator for another 48 hours, and finally, providers looked for residual tumor cells under an optical microscope at 40× magnification.

The VSD materials with some blood clots and soft tissues on the surface were pruned to a size of 1 × 1 × 0.3 cm and placed in a 10 × 10-cm Petri dish. The blood clots and soft tissues were singled out, cut into small pieces, and treated with 2 mL trypsin for 1 minute. Then, 6 mL FBS was used to neutralize the digestion of trypsin. Next, the mixture was centrifuged at 1,000 rpm for 3 minutes, and the precipitate was cultured under the same conditions as described above. The remaining pieces of VSD were washed three times with phosphate-buffered saline and centrifuged at 1,000 rpm for 3 minutes, and the precipitate was also cultured under the same conditions.

Staining of Cell Smears and Tissue Sections

After removing the VSD materials, the suspicious parts of the polyvinyl foam and drainage tube were fixed in 10% buffered formalin for 48 hours and then embedded in paraffin. The samples were sliced transversely at 4 μm on the embedded tissue blocks at 2.5-mm intervals and stained with HE. In addition, the clots in the tube were eluted for cell imaging and hematoxylin-eosin staining.

Statistical Analysis

The investigated clinical characteristics included inpatient stay, antibiotic consumption, drainage volume, time to wound closure, and infection rates. These clinical data were analyzed with SPSS (v 19.0; IBM Corp, Armonk, New York). The data were expressed as the mean ± SD. A Student t test was used to compare the parametric data, and a χ2 test was used to compare the intergroup differences of the count data. A two-tailed P value less than .05 was considered statistically significant. Study data are available from the corresponding author upon request.

RESULTS

The study included 50 men and 32 women with a mean age of 57.69 years (range, 15 to 76 years) at the time of surgery. The patients were followed for an average of 82.12 months (range, 6 to 156 months). All of the patients underwent preoperative staging, including plain radiographs as well as MRI and CT scans. The pathologic diagnoses included 28 chondrosarcomas, 23 osteosarcomas, 17 spindle cell sarcomas, 7 chordomas, and 7 other malignant tumors (Table 1). Of the 82 patients, 40 patients had VSD implanted into the large cavity to prevent infection and wound problems such as fat liquefaction and aseptic necrosis (VSD/intervention group), and the remaining 42 patients did not receive VSD (control group) because VSD was rarely used or because the patients had no large intracavity wounds. All 82 patients underwent en-bloc resection and pelvic reconstruction.

Table 1. - PATIENT CHARACTERISTICS
Characteristics n
Male/female 50/32
Mean age, y 57.69
Diagnosis 82
 Chondrosarcoma 28
 Osteosarcoma 23
 Spindle cells sarcoma 17
 Ewing sarcoma 5
 Melanoma 2
 Chordoma 7
Tumor stage 82
 I+II 14
 II+III 19
 I+II+III 15
 I+ IV 7
 I+II+IV 17
 I+II+III+IV 10

At the final follow-up, 42 patients had no evidence of disease. Seventeen patients had died (16 of metastatic disease) at an average of 16.4 months after surgery. The mean Musculoskeletal Tumor Society Score at the final follow-up was 72% (range, 35% to 85%).

Deep infection and wound problems were the most common complications, affecting 19 patients (23.2%). In the VSD group, only one patient (2.5%) suffered a superficial wound problem. However, in the control group, 18 patients (42.9%) had deep infection or wound problems. The patients in the control group had a significantly increased infection rate compared with the patients in the VSD group (P < .05).

Sixteen additional operations were performed to clean wounds, and culture-guided antibiotics were used to treat the infections. The remaining two infected patients were treated with sensitive antibiotics for 2 weeks, and dressing changes were performed every day with recombinant bovine basophilic fibroblast growth factor; those wounds healed 2 weeks later.

In addition, the VSD group had a significantly shorter duration of antibiotic use (7.23 ± 3.017 vs 11.39 ± 2.71 days), faster wound healing (17.42 ± 2.56 vs 25.22 ± 3.19 days), and a shorter inpatient stay (24.5 vs 36.7 days) than the control group (P < .05; Table 2). Thirteen patients experienced local recurrence (15.9%). Seventeen patients (20.7%) developed postoperative distant metastases at an average of 12.8 months (range, 5 to 19 months). An analysis of local recurrence was attempted; of the VSD patients, six had local recurrence (15%), and of those in the control group, seven did (16.7%); this difference was not significant (P < .05).

Table 2. - RESULTS
Parameter VSD Group Non-VSD Group P
Inpatient stay, d 24.5 36.7 <.05
Antibiotic use, d 7.23 ± 3.017 11.39 ± 2.71 <.05
Drainage, mL 482.3 ± 97.61 243.64 ± 53.83 <.05
Time to wound closure, d 17.42 ± 2.56 25.22 ± 3.19 <.05
Infection, n 1 18

No tumor cells were observed in the stained sections of the VSD materials, which were removed after the secondary operations. Moreover, after elution of all the removed VSD materials, the precipitate was cultured for 72 hours. No tumor cells were observed, but some white blood cells and fibroblasts were observed (Figure 2).

DISCUSSION

A well-functioning reconstruction after pelvic bone tumor resection is a challenge in orthopedic oncology. Complications are frequent, and functioning after the fact can vary.4,6 Recent findings show rates of infection ranging between 11% and 53%.1,4,7–9 Infection is the most common complication of pelvic resection for bone tumors.1,4 In the authors’ research, the infection rate for patients without NPWT was up to 42.9%. Patients’ poor overall health, long surgical time, large cavity, poor soft tissue coverage, and immunosuppression caused by neoadjuvant chemotherapy are major risk factors for the development of infection around prostheses and wounds.

In addition, it is difficult for the metal prosthesis to fuse with the surrounding soft tissues, which can lead to a large accumulation of fluid in the interstitial space that can increase the chance of bacterial infection over time. The insertion of a metal prosthesis increases the tension of soft tissue and skin fragility, leading to ischemia and soft tissue necrosis. A rectus abdominis myocutaneous flap and a gluteus maximus mucocutaneous flap are good choices for providing sufficient tissue coverage of dead space.10–12 A superomedial shift of the center of the hip, combined with iliac wing depletion and vancomycin-containing cement, can decrease deep infection by reducing dead space and improving soft tissue coverage, but this method lacks long-term follow-up study.13

In 1992, Fleischmann et al14 suggested VSD as NPWT to achieve rapid wound healing in traumatic soft wounds and chronic infections. After implanting VSD materials, the cavities are filled with foam and drainage tubes, and the wound is covered by a transparent vapor-transmitting polyurethane film. Medical-polymer polyvinyl hydration salt seaweed foam is used as a temporary skin substitute that is noncytotoxic with good biocompatibility and no skin irritation.15 The tubes are either drawn transcutaneously or placed epicutaneously, depending on the condition of the wound. When the drainage tubes are connected to a vacuum bottle, negative pressures are established. Critically, VSD has good histocompatibility and can maintain a stable negative pressure. Continuous negative-pressure suction can reduce wound exudate to prevent potential lacuna formation, improve local microcirculation, and stimulate the growth of granulation tissue.16 Such mechanisms result in a multilevel dynamic process that can prevent soft tissue infection and promote wound healing.17

Negative-pressure wound therapy has been widely used to treat large soft tissue defects and osteofascial compartment syndrome, and VSD dressings are used to fill breast cavities, facilitate polyacrylamide hydrogel implant migration, and prevent secondary infection.8 Although the application of NPWT for mastectomy using VSD has been reported, to the authors’ knowledge, this was the first time that VSD material was implanted into pelvic cavities.

The infection rate of patients receiving VSD was significantly reduced in the current study, and this is in accordance with results reported in an oral presentation at the 19th International Symposium of Limb Salvage in 2017.18 In the current study, only one patient (2.5%) in the intervention group had a superficial wound problem, which was lower than the 11% to 53% reported in previous studies of pelvic reconstruction using a prosthesis following tumor resection1,4,8,9 and was significantly lower than the 42.9% of control patients.

An issue of utmost concern is whether NPWT promotes the recurrence of pelvic malignant bone tumors. Finding residual tumor cells would be a key finding for investigating whether malignant bone tumors recur in the short term. Therefore, for the patients in the VSD group, after removing the VSD material, hematoxylin-eosin staining of the suspicious area was conducted, but investigators did not note residual tumor cells. In addition, negative cell culture results for the wound cavities’ washing fluid and VSD materials provide powerful evidence for the safety of NPWT with VSD material after the resection of pelvic bone tumors. To the authors’ knowledge, this was the first attempt to demonstrate the effect of NPWT on the recurrence rate in malignant pelvic bone tumors from a molecular perspective.

From the perspective of long-term follow-up, a previous report14 revealed local recurrence in 15% of patients receiving NPWT. In the current study, there was no significant difference in the local recurrence rates between groups. This result is comparable to those in the literature, wherein local recurrence rates range from 7% to 71% over short- and long-term follow-up periods.14,15

In the present study, when it was not certain that the tumor could be removed completely, VSD was not recommended. To minimize the possibility of VSD causing tumor cell growth, begin VSD 5 to 7 days after surgery. Continued monitoring for local recurrence in these patients is recommended, with CT or MRI of the pelvis performed according to the National Comprehensive Cancer Network guidelines.

In the VSD group, 20% of patients had distant metastases, which is comparable to other reported rates of 17% to 60%.2 There was no significant difference between rates of metastatic disease among VSD patients versus control patients.

Limitations

This study was retrospective and not randomized, so future multicenter randomized controlled trials with large sample sizes and more detailed research are needed. Although this was the first time that researchers attempted to demonstrate the safety of NPWT after the resection of malignant pelvic bone tumors, further molecular tests such as genetic immunofluorescence and flow cytometry would provide a stronger assessment of residual tumor cells.

CONCLUSIONS

Ultimately, investigators conclude that VSD for primary malignant pelvic tumor surgery with wide margins significantly reduced the risk of infection without an increased risk of recurrence or metastasis. Clinical use of NPWT with VSD warrants further study.

REFERENCES

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16. Shi B, Sun J, Cao Y, et al. Application of vacuum sealing drainage to the treatment of sea-water-immersed blast-injury wounds. Int Wound J 2016;13(6):1198.
17. Kaplan M, Daly D, Stemkowski S. Early intervention of negative pressure wound therapy using vacuum-assisted closure in trauma patients: impact on hospital length of stay and cost. Adv Skin Wound Care 2009;22(3):128–32.
Keywords:

clinical research; infection; malignancy; negative-pressure wound therapy; pelvic tumor; resection; tumor recurrence; vacuum-sealing drainage; wound care

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