UHM 2018, Vol. 45, No.

1 – HBO2 THERAPY FOR WOUND COMPLICATIONS AFTER VULVAR MALIGNANCY

Research Report
Hyperbaric oxygen therapy as adjuvant for treating wound complications
after extensive resection for vulvar malignancy
André Lopes, MD 1; Ronaldo Lúcio Rangel Costa, MD 1; Gabriel Lowndes de Souza Pinto, MD 1;
Mariana Camargo Guimarães Forghieri, MD 1; Ailma Larrè, MD 1; Thais Gomes de Almeida, MD 1;
Carla Baltazar de Souza, MD 1; Vivian Sartorelli, MD 1; Francisco Ricardo Gualda Coelho, MD 1;
José Ribamar Branco, MD 2
1 Gynecology Department, Instituto Brasileiro de Controle do Câncer, Sao Paulo, Brazil
2 Hyperbaric Medicine Department, Instituto Brasileiro de Controle do Câncer, Sao Paulo, Brazil
CORRESPONDING AUTHOR: André Lopes – andrelopes1002@hotmail.com
_____________________________________________________________________________________________________________________________________________________________________

ABSTRACT
Introduction: Necrosis, wound breakdown, and infection
represent major complications associated with radical vulvec-
tomy. We aimed to analyze the feasibility of hyperbaric oxygen
(HBO2) therapy as an adjunctive treatment for such complica-
tions.
Methods: We performed a retrospective analysis of the
medical records, clinical charts, and operative records of
vulvar cancer patients who underwent hyperbaric oxygen
therapy after extensive surgical resection in our institute between
2012 and 2016, with a comparison of the clinical out-
comes of patients with similar surgical procedures and
severe wound complications who did not undergo HBO2.
Results: A total of 16 patients were included in the study.
In the subgroup treated with HBO2, seven patients were
identified. Two patients had primary surgery, while five had
recurrent surgery (of these, two had previously undergone
radiation therapy). Six patients received reconstructive flaps
(five myocutaneous and one fasciocutaneous), while one patient
had primary suture. Dehiscence, ischemia and necrosis were
estimated to cover 30%-80% of the surgical surface area.
Surgical debridement was performed in six patients. Daily
90-minute sessions in the hyperbaric chamber were per-
formed at a pressure of 2.2 atmospheres absolute, with partial
oxygen pressure of 1672 mbar. Infection control and sat-
isfactory healing were achieved using 10-61 sessions. All
patients in the subgroup who did not receive HBO2 re-
quired surgical debridement due to partial or near-total flap
necrosis, with two reconstructive interventions required.
Conclusions: Hyperbaric oxygen therapy was an efficient
adjuvant for wound healing and infection control in manag-
ing wound complications after extensive vulvar resections.
INTRODUCTION
Wound breakdown, necrosis, and infection are among
the major complications associated with radical
vulvectomy for malignant neoplasms. Large resections
may be required to obtain clear margins, and the use
of surgical flaps is sometimes necessary, whether
for perineal reconstruction or restoration of sexual
function, resulting in an extensive wound [1–3].
The aggressive surgical strategy adopted in vulvar
cancer is associated with a significant rate of wound
complications, which is even higher in patients with
large tumors, previous radiotherapy, or preoperative
infection of the surgical site. Such complications
may lead to poor wound healing and may com-
promise the surgical outcome [4].
Hyperbaric oxygen (HBO2) therapy, which consists
of administering 100% oxygen at pressures higher than
normal atmospheric pressure, enhances the amount
of dissolved oxygen in the plasma, increasing O2
delivery to the tissue. HBO2 therapy has been used
in the treatment of various conditions, including ischemia
in surgical flaps, wound dehiscence and wound in-
fection, as well as to promote the recovery of
radiation-injured tissue [5].
In the present study, we aimed to describe the key
clinical and technical aspects related to the use of
HBO2 as an adjunct treatment for wound complications
after extensive vulvar resections.
METHODS
The study consisted of a retrospective analysis of the
records of patients with vulvar carcinoma treated via

_____________________________________________________________________________________________________________________________________________________________

KEYWORDS: vulvar cancer; wound complications; hyperbaric oxygen therapy

Copyright © 2018 Undersea & Hyperbaric Medical Society, Inc. 27

UHM 2018, Vol. 45, No. 1 – HBO2 THERAPY FOR WOUND COMPLICATIONS AFTER VULVAR MALIGNANCY

____________________________________________________________________________________________________________________________________________________

Table 1. Demographic, clinical, and operative characteristics of seven patients

with vulvar carcinoma treated with surgical resection and hyperbaric oxygen therapy
characteristic _______________________________ patient ________________________________
i ii iii iv v vi vii
____________________________________________________________________________________________________________________________________________________

baseline characteristics
age, years 42 57 70 85 93 76 79
previous radiotherapy no no no no yes no yes
____________________________________________________________________________________________________________________________________________________

comorbidities
diabetes mellitus no yes yes yes no no yes
overweight status no obese overweight no overweight no overweight
hypertension no no no no no yes no
____________________________________________________________________________________________________________________________________________________

operative details
treatment recurrent primary recurrent primary recurrent recurrent recurrent
histology squamous melanoma squamous squamous squamous squamous squamous
stage ii iiic iiic ib iiic iiic iiia
tumor size, mm 35 45 60 22 75 75 56
surgical flap bilateral bilateral unilateral primary unilateral unilateral bilateral
suture
flap type fascico- myocu- myocu- - myocu- myocu- myocu-
cutaneous taneous taneous taneous taneous taneous
flap source local gracilis tensor - gluteus gracilis gracilis
fascia lata maximus
____________________________________________________________________________________________________________________________________________________

postoperative course
days to dehiscence 12 6 16 12 10 5 20
area of dehiscence, 80 60 40 80 30 60 50
ischemia, and necrosis, %
HBO2 sessions 10 30 10 11 22 61 40
hospitalization, days 6 63 10 24 31 31 133
____________________________________________________________________________________________________________________________________________________

Vulvar melanoma was staged according to the 7th edition of the staging manual published by the American Joint Committee on Cancer.
Other vulvar cancers were staged according to the system put forth in 2009 by the International Federation of Gynecology and Obstetrics.

surgical resection in our institution between October
2012 and March 2016, followed by HBO2 for the treat-
ment of wound dehiscence, ischemia and infection.
Data regarding the characteristics of the patients, asso-
ciated clinical conditions, and features of the vulvar
neoplasia were collected. With the exception of vulvar
melanoma, which was staged as skin melanoma
according to the 7th edition of the staging manual pub-
lished by the American Joint Committee on Cancer,
other types of vulvar cancer were staged according
to the system put forth in 2009 by the International
Federation of Gynecology and Obstetrics [6,7]. Details
regarding prior treatment, type of surgical procedure
performed, and use of flaps for reconstruction were also
recorded, together with the results of the clinical evalu-
ation and further treatment of wound complications.
A comparison of the clinical outcomes of patients with
similar extensive vulvar resection and severe wound
complications who did not undergo HBO2 therapy was
performed. Regarding HBO2, the analysis included
technical aspects such as the number of sessions in the
hyperbaric chamber, as well as data regarding tolerance
to the treatment, clinical evolution and adverse effects.
RESULTS
A total of seven patients with vulvar carcinoma were
treated with extensive surgical resection in our insti-
tution between October 2012 and March 2016 and
received HBO2 for the treatment of wound dehiscence,
ischemia and infection (Table 1). Among these seven
patients included in our analysis, six were histologically
diagnosed with squamous cell carcinoma, while one

28 Lopes A, Costa RLR, Pinto GLS, et al.

UHM 2018, Vol. 45, No. 1 – HBO2 THERAPY FOR WOUND COMPLICATIONS AFTER VULVAR MALIGNANCY

_________________________________________________________________________________________

Table 2. Overview of clinical outcomes in patients

with vulvar carcinoma treated with surgical resection,
with or without hyperbaric oxygen therapy
patients hospital stay total surgical flap recurrent
median/days debridements loss disease
HBO2 7 27 6 0 3
No HBO2 9 31 10 2 3
_________________________________________________________________________________________

HBO2 = hyperbaric oxygen therapy

was diagnosed with malignant melanoma. The average
age in our study population was 70 years (age range,
42-85 years). Two patients had primary surgery, while
five had recurrent tumors, and two such patients had
previously undergone radiation therapy. Type II diabetes
mellitus was noted in four patients. Overweight status
or grade I obesity was also noted in four patients.
Preoperative infection of the surgical site was noted
in six patients, who were treated with antibiotics both
pre- and postoperatively.
Five radical vulvectomies were performed, two of
which involved bilateral inguinal lymphadenectomy and
en bloc resection with butterfly incision. Another patient
received wide perineal resection for recurrent disease
after vulvectomy, and the remaining patient underwent
resection for lymph node recurrence in the inguinal
region. Of the seven patients included in the analysis,
five underwent inguinal lymphadenectomy during the
same surgical procedure. Reconstructive flaps were
used in six patients, as follows: three patients received
a gracilis myocutaneous flap (bilateral in two patients
and unilateral in one); the remaining three patients
received a myocutaneous gluteus maximus flap, a myo-
cutaneous tensor fascia lata flap, and a bilateral fascio-
cutaneous local flap, respectively. The remaining patient
had primary suture. Three patients had distant meta-
stasis, one of whom also developed a local recurrence.
Wound breakdown occurred between the fifth and
20th postoperative days. The estimated area of dehis-
cence, ischemia and necrosis ranged from 30% to 80% of
the flap surface area. Surgical debridement of necrotic
tissue was performed in six patients. Postoperatively, all
patients received antibiotic therapy for a period of time.
The median length of hospital stay was 31 days (range,
six to 130 days). New surgical flaps were not required
in any patient. A representative example of the clinical
course for patients included in our analysis is provided
in Figure 1.
Sessions in the hyperbaric chamber took place daily,
lasted 90 minutes, and used a pressure of 2.2 at-
mospheres absolute, with a partial O2 pressure of
1672 mbar. The minimum number of HBO2 sessions
required to achieve infection control and satisfactory
healing was 10, while maximum number of sessions
was 61, with a median of 22 sessions. No adverse
effects related to HBO2 were reported.
We also performed a comparison of the clinical out-
comes of patients who were also treated with extensive
vulvar resection and had equally severe wound com-
plications but who did not undergo HBO2 therapy.
Nine such patients were treated between 2001 and
2014, four of whom had prior radiation treatment, and
three had recurrent disease. The patient characteristics
and clinical features were similar in patients treated
with HBO2 and those not treated with HBO2.
Among the nine patients who were not treated with
HBO2, all received radical vulvectomy, two involving
bilateral inguinal lymphadenectomy and en bloc resec-
tion with butterfly incision. The median length of hos-
pitalization was 27 days (range, eight to 55 days). All
patients received antibiotics. In seven of nine patients,
at least one myocutaneous flap was necessary, and all
such flaps required surgical debridement due to partial
flap necrosis (in one case, two surgical procedures
were required). A fasciocutaneous flap was performed
in the remaining two of nine patients, both with near-
total necrosis of the flaps requiring surgical interven-
tion. One of these patients required not only debride-
ment but also a myocutaneous gluteal flap, whereas the
other patient had surgical debridement with Z-plasty
and suture. No perioperative deaths were recorded
among the nine patients who did not receive HBO2, but
three patients had recurrent disease (one within less
than six months from the initial treatment) (Table 2).

Lopes A, Costa RLR, Pinto GLS, et al. 29

UHM 2018, Vol. 45, No. 1 – HBO2 THERAPY FOR WOUND COMPLICATIONS AFTER VULVAR MALIGNANCY

A B C

D E F

Figure 1. Peri- and postoperative photographs documenting the course of a recurrent squamous cell vulvar carcinoma
in a 79-year-old woman with a history of surgery and adjuvant radiotherapy (patient VII).
(A) Pre-operative state. (B) After radical resection. (C) After reconstruction with a bilateral myocutaneous gracilis flap. (D) Postoperative
wound breakdown, infection, and ischemia of the surgical flaps. (E) Wound healing and infection control after antibiotic treatment,
surgical debridement, and 40 sessions of hyperbaric oxygen therapy. (F) State at final follow-up (60 days after the end of the treatment).

DISCUSSION therapy encounter problems with wound healing.

Following radical surgery for malignant neoplasms of
the vulva, early complications are most frequently re-
lated to wound breakdown, infection and necrosis.
Such complications are associated with considerable
morbidity, and their incidence has been reported to be
up to 60%. However, limited information is available
regarding the management of such complications [2 8].
Locally advanced tumors, en bloc resection, radical
surgery, diabetes mellitus, history of malignancy, and
previous radiotherapy represent factors associated with
an even higher rate of complications. The management
of such patients poses a real challenge, as these local
complications may evolve into systemic manifestations
such as sepsis, which carry a high risk of death [8]. In
particular, patients who previously underwent radio-
Irradiated tissues result in reduced wound strength,
poor vascularization, diminished collagen deposition
and impaired formation of fibrotic tissue. These long-
term effects of radiotherapy may result in delayed
or even non-healing wounds with difficult clinical
management. HBO2 treatment has proven to be very
useful in enhancing the vitality and aiding the recovery
of previously irradiated affected tissues [9, 10].
Ischemia and necrosis of the surgical flap represent
serious complications after extensive vulvar resection.
HBO2 therapy has been found to promote flap salvage
and reduce the need for a new flap. Hyperbaric oxygen
improves the viability of compromised irradiated tissues
or that of tissues with hypoxia and decreased perfusion
[11]. Although surgical debridement of devitalized tis-

30 Lopes A, Costa RLR, Pinto GLS, et al.

UHM 2018, Vol. 45, No. 1 – HBO2 THERAPY FOR WOUND COMPLICATIONS AFTER VULVAR MALIGNANCY
sue was necessary in six of the seven patients included
in our analysis, there was no need for a new surgical
flap. As our analysis involved a small number of patients,
our observations do not have sufficient statistical power
to indicate that HBO2 was the sole contributor to the
favorable outcome of the surgical flaps. Nevertheless,
based on literature reports, the contribution of HBO2
in the recovery of devitalized tissues cannot be denied.
It should be noted that, while HBO2 therapy represents
a well-established strategy for the management of in-
fections and soft tissue necrosis, and moreover, is well
accepted as an adjunct treatment in surgical debride-
ment, HBO2 is neither required nor recommended in
patients with uncompromised flaps [9]. Overall, our
results indicate that HBO2 can play a significant and
positive role as an adjunct in the treatment of wound
complications. Surgical debridement of devitalized
tissues, antibiotic therapy, and daily care of the
surgical wound were equally important factors in
the surgical outcome.
The physiological action of HBO2 is related to the
increased oxygen supply. Short-term effects of HBO2
therapy include vasoconstriction and reduction of ede-
ma, which translates into anti-inflammatory activity
and phagocytosis activation with bacteriostatic and bac-
tericidal effect. Long-term effects of HBO2 treatment
are related to the high concentration of oxygen present
in the plasma during administration of HBO2, which
promotes neoangiogenesis and stimulates collagen pro-
duction by fibroblasts. Clinically, these effects translate
into faster wound healing, better infection control and
enhanced recovery of previously irradiated tissues [9,11].
Regarding the possible recurrence of the disease in
oncological patients exposed to hyperbaric oxygen,
HBO2 is considered safe for use in patients with malig-
nant neoplasms, as indicated by several research articles
and systematic reviews. There is currently no evidence
indicating that HBO2 acts as a stimulator of tumor
growth or recurrence, although limited data are avail-
able regarding the use of HBO2 in patients with vulvar
cancer. Of our seven patients who received HBO2
therapy, three developed distant metastasis, one of
Lopes A, Costa RLR, Pinto GLS, et al.
whom also had local recurrence. All three patients
with recurrence had poor prognosis, with locally ad-
vanced disease and lymph nodes positive for macro-
metastasis. Only one patient had a disease-free interval
of less than six months after HBO2. Therefore, it is
unlikely that the observed recurrences were related
in any way to the use of HBO2 [10,12,13,14].
While HBO2 therapy is usually well tolerated, ad-
verse effects may occur during the treatment, including
feelings of anxiety and claustrophobia, as well as dis-
comfort related to the difficulty in equalizing pressure
in the middle ear. Oxygen-induced side effects may
also occur, including myopia (usually temporary)
and convulsions, the latter being less frequent but
more serious. In our study, good tolerance for HBO2
was observed in all patients, and none of the treat-
ments was discontinued because of adverse effects [5].
CONCLUSIONS
Our retrospective analysis of clinical records of vul-
var cancer patients treated with surgical resection re-
vealed that HBO2 used as adjunctive treatment may
have played a key role in the control of surgical site
infection, in the healing process, and in the recovery
of ischemic flaps. Based on the results of our present
study, we conclude that HBO2 can provide good results
in the treatment of wound complications after exten-
sive vulvar resections. As our study had a retrospec-
tive design and included a very small sample, further
research is warranted to confirm the generalization of
our findings for vulvar cancer patients and to determine
the effect of HBO2 on certain types of cancer, as well
as to clarify the mechanisms underlying these effects.
Acknowledgments
This research received no support from a specific grant in the
public or private sector.
The authors declare no conflicts of interest exist with this
submission.
31
UHM 2018, Vol. 45, No. 1 – HBO2 THERAPY FOR WOUND COMPLICATIONS AFTER VULVAR MALIGNANCY
_____________________________________________________________________________________________________________________________________________________________________
REFERENCES
1. Höckel M, Dornhöfer N. Vulvovaginal reconstruction for
neoplastic disease. Lancet Oncol. 2008; 9: 559-568.
2. Leminen A, Forss M, Paavonen J. Wound complications in
patients with carcinoma of the vulva. Comparison between radical
and modified vulvectomies. Eur J Obstet Gynecol Reprod Biol. 2000;
93: 193-197.
3. Baiocchi G, Mantoan H, de Brot, et al. How important is the
pathological margin distance in vulvar cancer? Eur J Surg Oncol.
2015; 41: 1653-1658.
4. Hampson NB, Holm JR, Wreford-Brown CE, Feldmeier J.
Prospective assessment of outcomes in 411 patients treated with
hyperbaric oxygen for chronic radiation tissue injury. Cancer. 2012;
118: 3860-3868.
5. Weaver LK. Hyperbaric oxygen therapy indications. 13th ed.
North Palm Beach, FL: Best Publishing Company, 2014.
6. Edge SB, Compton CC. The American Joint Committee on
Cancer: the 7th edition of the AJCC cancer staging manual and the
future of TNM. Ann Surg Oncol. 2010; 17: 1471-1474.
7. Pecorelli S. Revised FIGO staging for carcinoma of the vulva,
cervix, and endometrium. Int J Gynaecol Obstet. 2009; 105: 103-104.
8. Reedy MB, Capen CV, Baker DP, Petersen WG, Kuehl TJ.
Hyperbaric oxygen therapy following radical vulvectomy: an
adjunctive therapy to improve wound healing. Gynecol Oncol. 1994;
53: 13-16.
32
9. Kalns JE, Dick EJ Jr, Scruggs JP, Kieswetter K, Wright JK.
Hyperbaric oxygen treatment prevents up-regulation of angiogenesis
following partial-thickness skin grafts in the pig. Wound Repair
Regen. 2003; 11: 139-144.
10. Feldmeier J, Carl U, Hartmann K, Sminia P. Hyperbaric oxygen:
does it promote growth or recurrence of malignancy? Undersea
Hyperb Med. 2003; 30: 1-18.
11. Bennett MH, Feldmeier J, Hampson NB, Smee R, Milross C.
Hyperbaric oxygen therapy for late radiation tissue injury.
Cochrane Database Syst Rev. 2016; 4: CD005005.
12. Feldmeier JJ, Heimbach RD, Davolt DA, Brakora MJ,
Sheffield PJ, Porter AT. Does hyperbaric oxygen have a cancer
causing or -promoting effect? A review of the pertinent literature.
Undersea Hyperb Med. 1994; 21: 467-475.
13. Daruwalla J, Christophi C. Hyperbaric oxygen therapy for
malignancy: a review. World J Surg. 2006; 30: 2112-2131.
14. Moen I, Stuhr LEB. Hyperbaric oxygen therapy and cancer—
a review. Target Oncol. 2012; 7: 233-242.
✦
Lopes A, Costa RLR, Pinto GLS, et al.