Surgical Science, 2013, 4, 464-468
http://dx.doi.org/10.4236/ss.2013.410091 Published Online October 2013 (http://www.scirp.org/journal/ss)
Evaluation of an in Situ Polymerizing Hydrogel Applied in
Tumor Excision Cavities during Breast
M. Korell1, F. Brassel2, G. Bilir3, J. Pagels3
1Department of OBGYN, Johanna Etienne-Krankenhaus, Neuss, Germany
2Department of Radiology, Klinikum Duisburg, Duisburg, Germany
3Department of OBGYN, St. Josef Krankenhaus, Moers, Germany
Received September 14, 2013; revised October 12, 2013; accepted October 20, 2013
Copyright © 2013 M. Korell et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Study Objective: To evaluate the imaging characteristics and healing following application of an absorbable biocom-
patible hydrogel into the excision cavity following breast conservation surgery. Design: Non-randomized study evalu-
ating hydrogel application feasibility, post-operative hydrogel imaging characteristics, cavity healing following hy-
drogel absorption and the resulting breast cosmesis. Setting: Teaching hospital University of Essen, Germany. Patients:
Seven (7) patients underwent unilateral or bilateral breast conservation surgery to remove cancerous or benign tumors.
Interventions: All patients received hydrogel application following primary tumor excision. Imaging performed in the
first postoperative week included ultrasound, MRI and CT. Breast cosmesis scores were obtained at one and three
months following surgery. Measurements and Main Results: While preliminary, a relationship between percent cavity
filling and drainage was observed, with 30% or more cavity filling resulting in decreased drainage. Additionally, the
hydrogel was readily visible under ultrasound, MRI and CT imaging modalities. Finally, patients were satisfied and
surgeons felt that patient cosmesis was improved relative to their prior experience. Co nclusion: Initial data suggest that
hydrogel filling may reduce excision cavity drainage, which may reduce seroma or hematoma formation. Additionally,
these gels may improve cavity visibility and stability, furthering the use of partial breast irradiation. Finally, while more
studies are required, these materials may have a role in improving long term patient cosmesis.
Keywords: Lumpectomies; Breast Radiation; Seroma Prevention; Breast Cosmesis
The current standard of care for the surgical treatment of
patients diagnosed with breast cancer is breast conserva-
tion surgery (BCS, frequently called lumpectomy)
whenever it is possible. The BCS procedure involves
removal of the breast cancer along with a margin of
normal breast tissue, followed routinely by whole breast
radiation therapy (WBRT) to eliminate potential tumor
cells beyond the resected margins. In addition to pre-
serving much of the patient’s breast tissue, this technique
has been shown to be as efficacious as mastectomy, with
similar survival rates over 15 years of follow up [1-4].
For further reduction of local breast cancer recurrence,
a radiation boost is applied to the tumor bed, which is
guided by using metal clips as marker. This approach is
justified since cancer recurrence is highest near the exci-
sion site, with 86% of recurrences in the same quadrant
as the excision, as shown in one multicenter study .
However, unlike many other radiation oncology targets
(i.e. prostate), the margins of the excised cavity are often
difficult to visualize following surgery, as demonstrated
by large inter-observer differences while attempting to
delineate and contour the cavities [6-8]. Surgical clips are
often used to mark discreet points within the cavity, but
the vast majority of the cavity margins remain unmarked,
and often difficult to delineate. Frequently seromas
and/or hematomas form within the excision cavities fol-
lowing surgery, assisting in cavity visualization, but se-
roma formation is an unpredictable complication of BCS
and therefore is not a reliable aid for visualization.
Further complicating cavity targeting is the change in
cavity volume due to seroma absorption in the months
following surgery. Several researchers reported changes
in mean excision cavity volumes during radiation therapy
opyright © 2013 SciRes. SS
M. KORELL ET AL. 465
ranging from 22.5% to 54% [9-13]. Cavity volume
change during radiation can result in movement of nor-
mal tissue into the radiation treatment volume, or worse,
movement of the cavity margins, potentially containing
residual tumor cells, out of the radiation treatment vol-
A marker that allows for improved post-operative
identification and localization of the excision cavity
margins while preserving the cavity volume through the
course of radiation therapy would overcome a number of
the challenges related to partial breast irradiation. Further,
stable and visible cavity margins would facilitate accel-
erated partial breast irradiation (APBI), which has been
reported to be about half the cost of WBRT .
The aim of this study is to gather initial clinical data
on the use of in situ polymerizing polyethylene (PEG)
hydrogel instilled into lumpectomy cavities to facilitate
postoperative cavity visibility via ultrasound, MR and
CT imaging. Additional study endpoints include patient
comfort and tolerance of implant, breast drainage, physi-
cian scored cosmesis at 1 and 3 months following im-
plantation, and collection of adverse events experienced
2. Materials and Methods
Following institutional Ethics Committee protocol ap-
proval and receipt of Informed Consent, a total of 7 pa-
tients were enrolled in this evaluation. Patient ages
ranged from 19 to 75 years (mean = 47 years), and 4 of
the patients had benign disease, while 3 patients had been
previously diagnosed with breast cancer. 6 of the patients
had unilateral procedures, while one patient had bilateral
lumpectomies, resulting in 8 hydrogel instillations. Tu-
mor volumes ranged from 1 to 165 cc, with a mean vol-
ume of 63 cc.
Following completion of tumor excision and confir-
mation of cavity hemostasis, one drainage catheter was
tunneled into the cavity, and one silicone instillation
catheter was introduced into the excision cavity via the
surgical incision. With the drainage catheter clamped to
prevent plugging, between 4 to 20 ml of hydrogel (mean
= 14 ml) was instilled via the silicone catheter, which
was withdrawn from the cavity prior to hydrogel polym-
erization (Figure 1). All but one of the cavities were par-
tially closed with sutures prior to injection, and depend-
ing on incision location, half of the skin incisions (4 of 8)
were mostly closed prior to hydrogel injection to prevent
loss of liquid hydrogel precursor while the hydrogel po-
The hydrogel used in this evaluation was a polyethyl-
ene glycol (PEG) based hydrogel initially approved in
Europe for use as a dura mater sealant, but subsequently
approved for use on the lung, in vascular surgery and for
the prevention of peridural adhesions following spinal
Figure 1. Injection of hydrogel precursors into the lumpec-
tomy cavity, where they polymerized forming a soft, ab-
surgery (Confluent Surgical, Bedford, MA, USA). Fol-
lowing mixing of the two precursor solutions, a reaction
between end-functionalized PEG and trilysine results in
polymerization, or creation of a soft, solid hydrogel,
within seconds without producing measureable heat. The
resulting hydrogel contains hydrolysable linkages at each
PEG-trilysine junction, causing the hydrogel to break
down over time and be absorbed. For this application
both precursors were diluted 1:1 with sterile saline prior
to applicator assembly using a commercially available
mixing Y-connector (Micromedics, Inc. St. Paul, MN,
USA). This dilution slightly slowed down the polymeri-
zation rate reducing the likelihood of applicator plugging
during instillation, and reduced the absorption time to
within 1 month (as demonstrated by prior testing in 37˚C
PBS). While the relatively short persistence of this mate-
rial will not make it an ideal candidate for partial breast
radiation targeting, it will still provide valuable informa-
tion regarding hydrogel visualization, injection feasibility,
patient tolerance, cosmesis, and could potentially benefit
the patient by reducing drainage and the likelihood of
Following surgery ultrasound (US) images of cavities
were obtained within 2 days, and drains were removed
between 1 and 5 days (mean = 3 days), with the total
drainage recorded. In addition to US images, magnetic
resonance (MRI) or computed tomography (CT) images
were obtained within one week of surgery. At the 1
month postoperative visit the surgeon queried patients
regarding postoperative pain, and scored both postopera-
tive pain and treated breast cosmesis as either worse than
expected (score of −1), as expected (0) or better than
expected (1, relative to hospital experience). At 3 months
following surgery the treated breast cosmesis was scored
as before, along with a patient´s estimation of breast
cosmesis score using the visual analogue scale (VAS),
with a range from 0 (completely unsatisfied) to 10 (very
All three of the breast cancer patients received postop-
Copyright © 2013 SciRes. SS
M. KORELL ET AL.
erative chemotherapy and whole breast radiation.
The course of healing for all patients was normal, al-
though one patient experienced a superficial wound in-
fection that resolved within three weeks without further
treatment. Overall the postoperative pain was scored as
either less than normal, or normal to the surgeon’s clini-
Breast drainage ranged from 5 to 180 ml (mean = 59
ml, median = 8 ml). Of note, 94% of the total study
drainage came from the three patients with the largest
lumpectomies. In the other breasts drainage averaged 6
ml. A sharp drop in drainage was noted when the gel
volume was greater than 30% of the cavity volume (Fig-
In every patient the hydrogel was readily apparent un-
der US imaging. Initially the hydrogel had a hypointense
appearance, like water. Over time gel absorption was
observed (Figure 3).
The gel was found to be readily visible using MR im-
aging, as seen in Figure 4. The gel is most conspicuous
using T2 with fat suppression, although it is visible under
all modalities. In cases with low drainage the cavity had
a much more uniform density, suggesting a better cavity
fill and less fluid collection (as seen in Figure 4(a)). In a
patient that exhibited 180 ml of drainage (with 12% cav-
ity filling), different densities are visible within the cav-
ity suggesting both fluid and gel collections, as seen in
Figures 4(c) and (d).
The hydrogel was also visible under CT imaging at
one week following implantation, with a good agreement
between US and CT cavity shapes (Figure 5).
Patients satisfaction with the outcome at 3 months
postoperatively was high: mean = 8.8 (min 8 – max 9.5).
Surgeon scored breast cosmesis at one and three
months following surgery was scored as “Better than
expected” (50%, 62.5%), “As expected” (50%, 25%) and
“Worse than expected” (0%, 12.5%), respectively. Using
the scoring method outlined earlier, this represents a 50%
Figure 2. Postoperative drainage was observed to drop
when the gel volume was at least 30% of the lumpectomy
Figure 3. Hydrogel appearance under ultrasound imaging
in a single patient at 1 day (a), 1 week (b), and at 14 weeks
(c) following implantation.
Figure 4. Six days following implantation the gel is clearly
visible under MRI using fat suppression with both T2 (a),
and T1 with contrast (b). Differing densities within the cav-
ity of one patient suggested both fluid and gel collections at
7 days with T2 and fat suppression (c), and with T1 and no
fat suppression (d). Scale = 1 cm.
improvement in cosmetic outcome at both time points,
relative to prior surgeon experience (Figure 6).
Some of the patient care challenges following breast
conservation surgery include 1) avoiding the formation
of symptomatic seroma or hematoma, 2) accurate identi-
fication of the tumor cavity margins for targeted radio-
therapy during either PBI or boost procedures, 3) the
change in cavity volume over time, also limiting the po-
tential use of PBI, 4) the long term cosmetic result due to
Copyright © 2013 SciRes. SS
M. KORELL ET AL. 467
Figure 5. Close agreement between ultrasound image (a)
and CT image (b) in patient one week following surgery.
Scale = 1 cm.
Figure 6. Surgeon scored breast cosmesis one and three
months following surgery show ed a 50% improvement rela-
tive to prior surgeon experience.
volume loss and scar tissue retraction, and 5) impact on
tissue visualization during subsequent diagnostic imaging
procedures (mammography) due to scar formation.
The hydrogel used in this evaluation has been ap-
proved and used as a sealant and adhesion barrier in dif-
ferent areas of the body. As such, these features may
have a role in improving outcomes following BCS. These
materials have the potential to reduce the incidence of
postoperative seroma and hematoma formation by both
acting as a cavity filler, and by sealing the cavity walls to
prevent fluid migration into the cavity. While limited in
sample size, the data from this preliminary study suggest
that when at least 30% of the cavity volume is replaced
with hydrogel that seals the cavity margins, postoperative
drainage, and presumably postoperative seroma forma-
tion, may be reduced.
Additionally, while the hydrogel utilized for this
evaluation will likely not last long enough for PBI, it
may provide adequate cavity delineation and stability for
accelerated PBI. Imaging with both MRI and CT demon-
strated hydrogel visibility, leaving open the possibility of
contouring the hydrogel during radiation treatment plan-
ning. Indeed, recent studies in cadavers with similar cav-
ity filling hydrogels demonstrates that these materials can
be contoured with CT, and if a 15 mm treatment margin
is utilized due to improved cavity visibility, then the total
radiation dose to the normal breast tissue, heart and lungs
can be reduced .
Another potential benefit of hydrogel excision cavity
fillers is an improvement in patient cosmesis. Permanent
fillers could result in long term volume replacement,
preventing contour deficits. Absorbable fillers, while not
providing long term volume replacement, may also im-
prove cosmesis by allowing tissue filling of the cavity
during absorption, or by reducing the scar formation and
subsequent scar retraction which can lead to scar invagi-
While this evaluation is very preliminary, it does
demonstrate some of the potential advantages on excision
cavity filling with hydrogels at the time of surgery. These
materials have the potential to reduce seroma formation,
improve cavity visualization and delineation, and to im-
prove long term patient cosmesis. These results warrant
further clinical research of this technique.
The authors would like to thank Alex Norbash, MD for
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