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Lymphedema after Gynecological Cancer
Tanja Planinsek Rucigaj*
Head of the Clinic, Department of Dermatovenereology, University Medical Centre Ljubljana,
Slovenia
*Corresponding author: Tanja Planinsek Rucigaj, Department of Dermatovenereology,
University Medical Centre Ljubljana, Slovenia, Email: [email protected]
Published Date: February 16, 2017
ABSTRACT
Lymphoedema because of a disruption of the lymphatic system after gynecologic cancers
treatment is increasing. It increase because of increasing the cervical, uterine, ovarian and vulvar
carcinomas. The lymphoedema has big negative influence on quality of life of cancers survivors.
With appropriate therapy and education about lymphoedema their quality of life will be better.
Keywords: Gynecologic cancer; Vulvar cancer; Ovarian cancer; Endometrial cancer; Cervical
cancer; Lower extremity lymphoedema; Quality of life
INTRODUCTION
Lymphoedema is acute or chronic swelling the part of the body. It present a disruption of
the lymphatic system [1,2]. Lymphoedema occur when the lymphatic system can not maintain
tissue fluid homeostasis, resulting in the accumulation of protein-rich fluid in the subcutaneous
layer [3,4]. Cancer and its treatment (surgery and radiotherapy) and recurrences can cause
lymphoedema at any time to lower extremities [5]. Lymphoedema is most commonly seen on
lower limbs. This process may take several years [6].
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Lymphoedema in the leg after gynecological cancer treatment is caused by lymphatic stasis
which causing the accumulation of protein, metabolites of protein and hyaluronic acid in the
extracellular place. This is increasing the tissue colloid osmotic pressure and leads to water
accumulation and increasing the interstitial hydraulic pressure. In edematous tissue we can found
increased numbers of fibroblasts and inflammatory cells, adiposities, and keratinocytes, collagen
deposits and connective tissue overgrowth. Basement membrane of lymphatic vessels is ticker,
we found fragmentation and degeneration of elastic fibers and increased of ground substance too.
Thus causing progressive subcutaneous fibrosis [7-10].
Acute lymphoedema is usually transitional. It resolves in 18 to 25 months post surgery.
But chronic lymphoedema is persistent and cause fibrosis and scarring. In the acute stage the
oedema is “pitting”. The chronic inflammatory processes at lymphoedema affect the skin and
subcutaneous tissues and depositis of fibrosis and adipose tissue causes the firmer and less easy
“pit” swelling [4,11,12].
The International Society of Lymphology was classified lymphoedemas in 4 stages. Stage 0 is a
subclinical condition in which swelling is not evident. But impaired lymph transport is present. In
stage I an early fluid accumulation is subsiding with limb elevation. In stage II is manifesting the
pitting oedema and limb elevation rarely reduces tissue swelling. Stage III includes lymphostatic
elephantiasis in which we not found the pitting but skin changes, such as acanthosis, fat deposition
and fibrosis [3,13,14]. The severity of lymphoedema was classified based on interlimb discrepancy
in mild (<20%), moderate (20%–40%) and severe (>40%) [3].
Most gynecologic cancers surgery involves removal of the uterus, and cervix, ovaries and
fallopian tubes, with node dissection. Lymphadenectomy is an integral part of gynecological cancer
surgery: complete pelvic lymphadenectomy with removal of all fatty lymphatic tissue from the
predicted areas of high incidence of lymph nodes with possible metastatic involvement and paraaortic lymphadenectomy with removal of all lymphatic tissue from the aortic region or sentinel
node procedures which benefit is under investigation [15]. At ovarian cancer, the omentum is
removed too. In patients with advanced ovarian cancer systematic lymphadenectomy prolongs
the survival rate. In patients with vulvar cancer removal of pelvic, iliac and obturator lymph nodes
is not been proven to result in an increased of survival rate. Lymphadenectomy in endometrial
cancer in stages I G1 and G2 has not been shown an increase in the survival time [15]. Radiation
and chemotherapy are commonly part of the treatment plan for women with gynecological
cancer [16]. Lymphoedema can show on recurrences [5] and metastases increase the risk for
lymphoedema too. Lymphoedema can occur days, months or years following gynecological cancer
surgery with lymph node removal and/or radiation [17].
VULVAR CARCINOMA
Vulval cancer was in 2014 in UK the 20th most common cancer among females, accounting for
less than 1% of all new cases of cancer in female cases. In 2014, there were 1,289 new cases of
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vulval cancer in the UK. The crude incidence was 3,9 new vulval cancer cases for every 100,000
females in the UK [18-21]. In Slovenia were in 2013 43 new cases of vulvar carcinomas [22].
Squamous cell carcinomas represent more than 90% of vulval cancers. The other were
melanomas, sarcomas, basal cell carcinomas and adenocarcinomas [23,24].
Lympatic Drainage of the Vulva
The lymphatic drainage of the vulva go through the inguinofemoral triangle [25].
UTERINE CARCINOMA
Uterine cancer was the fourth most common cancer in females in the UK in 2014, accounting
for 5% of all new cases of cancer in females [18-21]. Endometrial carcinoma mainly occurs at
post-menopausal women. There were 9,324 new cases of uterine cancer in 2014 in the UK [1821]. The crude incidence in the UK in 2014 were 28,4 new uterine cancer cases for every 100,000
females. The crude incidence in the Slovenia in 2013 was 29,9 new uterine cancer cases for every
100,000 females [22].
Histologically the cancers are adenocarcinomas.
Lympatic Drainage of the body of the Uterus
The body of the uterus drains through the external iliac nodes, some small parts through
internal iliac nodes and the superficial inguinal nodes along the round ligament [26].
CERVICAL CARCINOMA
Cervical cancer was in 2014 in UK the 13th most common cancer among females, accounting
for 2% of all new cases of cancer in females. In 2014, there were 3,224 new cases of cervical
cancer in the UK. The crude incidence rate were around 10 new cervical cancer cases for every
100,000 females in the UK in 2014 [18-21]. More than half (52%) at females aged under 45 years
[27]. The crude incidence in the Slovenia in 2013 was 11,9 new cervical carcinoma cases for every
100,000 females [22].
The two thirds of cervical cancers are squamous cell carcinoma and around 15% are
adenocarcinoma [28-31]. Aetiology of cervical carcinoma is mainly due to infection with human
papilloma virus types 16, 18, 31, 33, 45, 51, 52 and 56.
Lympatic Drainage of the Cervics uteri
Lymph nodes which drainage the lymph from cervics uteri are the internal iliac and external
iliac lymph nodes and nodes from the presacral, parametrical and pararectal areas [32] .
OVARIAN CARCINOMA
Ovarian cancer is continuously increasing. Ovarian cancer was in 2014 the sixth most common
cancer among females in the UK, accounting for 4% of all new cases of cancer in females [14,18-
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21,33]. There were 7,378 new cases of ovarian cancer in the UK in 2014 . The crude incidence was
22,5 new ovarian cancer cases for every 100,000 females in the UK in 2014 [18-21]. The crude
incidence in the Slovenia in 2013 was 17,0 new ovarian cancer cases for every 100,000 females
[22].
The 80-90% of ovarian malignancies are primary epithelial tumors (cystadenocarcinoma
in 50% of all cases., mucinous cystadenocarcinoma, and endometrioid and mesonephric
malignancies.). Other rarer subtypes include germ cell tumours in pre-menopausal women [3436].
Lymphatic System of the Ovary
The lymph drainage of the ovary follows blood supply at the infundibulopelvic ligament and
then go to the paraaortic and precaval lymph nodes. From the hilus of the ovary lymphatic pathway
crosses the broad ligament draining into the obturator, external, and common iliac nodes [37].
Lymphoedema after Gynecologica cancers
Improvements in survival among patients with gynecologic cancer have long-term sequelae
and more patients are at risk for developing lymphoedema, which has received minimal attention
[16]. Postoperative lymphoedema of the lower extremity incidence increased over time. Same
suggest that the best for risk reduction of that lymphoedema is postoperatively inclusion of the
patient in education program [38]. The education in combination with physiotherapy can reduce
the risk of breast cancer-related lymphoedema [39]. But assessment and management strategies
for lymphoedema on upper-extremity cannot be directly transferred to lymphoedema on lowerextremity. Limb size, volume and location create distinctive characteristic between lymphoedema
development following node dissection for breast cancer from lymphoedema following node
dissection in gynecologic cancer.
To confirm an early diagnosis of lymphoedema there is no standard methods. Nesvold and his
co-workers were noted that a lack of information that were given to the patient after surgery is
a cause of delay diagnosis of lymphoedema [40]. Lymphoedema of the leg is a major long-term
complication of radical surgery after cervical, endometrial, and ovarian cancer. Overall incidence
of lymphoedema was 21.8% at stage 1 in 60%; at stage 2 in 32% and at stage 3 in 8%. Cumulative
incidence increased during the time 12.9% at 1 year, 20.3% at 5 years and 25.4% at 10 years [4143].
The prevalence of lymphoedema of the leg in patients with gynecologic malignancies varies
according to the anatomical origin, way of treatment and infection following the surgical tretment
[44]. Same study show differences in appearing lymphoedema of the leg depending the stage of
disease nad same not [14,42,43,45-48].
Highest rate of lower leg lymphoedema is after dissection of lymph node because of
gynecological cancer (50–62.2%) and is related to number of resected lymp nodes [14,48].
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Lymph vessels and Lymph nodes
Radiation, because the soft tissue is replaced by scar tissue and apoptosis of lymphatic
endothelial cells, causes a dose-dependent long-term decrease in lymphatic function because
of both lymphatic vessel and soft tissue fibrosis. That leads to increasing of expression of
transforming growth factor-β1 (TGF-β1) and endothelial growth factor-C (VEGF-C). That
has an antilymphangiogenic effects by inhibiting LEC proliferation and tubule formation [4953]. Lymphoedema is rare after radiation therapy alone. When radiation therapy following
lymphadenectomy is for ten time increasing the risk for lymphoedema [54].
Lower extremity lymphoedema occurs in 9% to 70% of patients with vulvar cancer, 1.2% to
47% of those with cervical cancer, 1.2% to 17.7% of those with endometrial cancer, and 7% to
40.8% of those with ovarian cancer [14,42,43,45-48]. After gynecological surgery the diagnosis of
lymphoedema was made in 18%. 53% of of women develop lymphoedema of the leg in 3 months,
18% in 6 months, 13% in 12 months and other in 16% in 5 years after treatment.
Lymphoedema after treatment of Vulvar cancer
Women after surgery and radiotherapy of vulvar cancer develop lymphoedema in 47% [48].
Complications after radical vulvectomy and bilateral groin dissection are wounds, lymphocysts
and infection of the groin and lymphoedema of the legs and we can found them in more than two
thirds of women [55]. Because of those complications and predictable anatomic drainage pattern
in this region, lymphatic mapping and sentinel node dissection is best solution for the women
with vulvar cancer [25,37].
Lymphoedema after treatment of Ovarian cancer
Women with ovarian cancer have a lower incidence of lower limb lymphoedema than patients
with uterine cancer. 7- 40.8 % of women after therapy of ovarian cancer developed lymphoedema.
Post-operative radiotherapy is an independent risk factor for lymphoedema. Para-aortic lymph
node dissection was not a significant risk factor for lymphoedema [43,46,48,56]. In 86.2% the
lower limb lymhoedema is developed within 12 months after surgery and take a more than 6
months in 62.1% of the women [45].
The number of resected lymph nodes seems to be directly proportional to the potential risk of
later developing lymphoedema after therapy of ovarian cancer [37]. Ki and his co-workers found
a lymphoedema of the leg after surgery in 15.0 ± 20.1 months (range, 0.15–103 months). 67.4%
within 12 months, 10.9% within 13 to 24 months, 10.9% within 25 to 36 months, and 10.9% after
37 months [14,37].
Lymphoedema after treatment of Endometrial cancer
At more than one-third of patients with primary endometrical cancer after dissected pelvic
lymph nodes and postoperative radiotherapy were found the lower leg lymphoedema. The
lymphooedemas were lasted for more than 12 months in most women [57].
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Patients with lymph nodes removed at initial surgery had in 2,4 % lymphoedema. Patients
who had 10 or more regional lymph nodes removed have lymphoedema in 3,4%. Lymphoedema
was noted after 5.3 months after surgery and was unilateral in 69% and bilateral in 31%. At 75%
it was in stage I and other in stage II [37,58,59].
Lymphoedema after treatment of Cervical cancer
Patients with cervical cancer who have radiotherapy after laparoscopic surgical therapy
developed the lymphoedema in 69.0%. Patients with primary radiotherapy developed the
lymphoedema in 11.6% [48,60]. 95% of women who have radical surgery with lymphadenectomy
for cervical cancer FIGO stage I to stage IIA developed the lymphoedema. 78.7% of the women
developed the lymphoedema within 3 years after treatment [37,47,61,62].
Quality of Life
At the cancer survivors have lymphedema a profound effect. It effect on their quality of life [48].
Women are described depression, anxiety and fear of dying, fatigue, pain, bladder dysfunction
and vaginal problems [63]. 29% of 199 survivors reported about anxiety and 24% of them
fear of the recurrence of the disease [64]. At patients with lymphoedema we found numbness
(40.8%), tightness (22.5%), feeling of swelling (22.5%), heaviness (22.5%), limited movement of
knee (21.1%), soreness (21.1%), leg or foot feel weakness (18.3%), stiffness (15.5%), increased
temperature in the leg (12.7%), limited movement of ankle (11.3%), and limited movement of
foot (11.3%) [45].
The lymphoedema has influence on quality of life due to a combination of the pain, impaired
social and psychophysical function. For this purpose we can use the Quality of life assessment
questionnaires (as SF-36 or validaded condition-specific questionnaires). Their use may helps us
in the planning of treatment and the monitoring of the effectiveness the treatment of lymphoedema
[65,66].
Our expiriences with lymphoedema after Gynecological cancer
We performed a retrospective study of 64 women with secondary lymphoedema
after a gynecological (cervical, uterine, ovarian, vulvar) cancers. Women were treated at
Dermatovenereological Clinic, University Medical Centre Ljubljana from 2004 to 2010.
Only 37,2 % of women after gynecological cancer, according to the published reports, were
referred to our only out/inpatients department in the country [67].
The average time from cancer treatment to they first received appropriate therapy of
lymphoedema was on average 7,4 years (Table 1) [68].
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Table 1: Data about patients with secondary lymphoedema after gynecological cancer.
Another retrospectiv study was study about quality of life of patients with secondary
lymphoedema. We were comparated patients with lymphoedema of the arm (post mastectomy)
and leg (after gynecological cancer) between September 2013 to end of January 2014. 163 women
were included.
Patients with lymphoedema of the arms and legs fil the same questionary with 10 questions
(10 question qustionary of quality of life of dermatology patients is only validated questionary in
Slovenia) about their life before therapy with short strech bandages and after one year of therapy
of lymphoedema with round knited stockings class III or sleeve class II.
Oedemas on the legs have biger worse influence on quality of life than arm oedemas (11,92 vs.
8,93 before therapy).
After therapy, quality of life at patients with leg oedemas was better for 54,53%, and with arm
oedemas for 44,79%.
Patients with left leg oedemas have more problem than those with right leg oedemas (12,83
vs. 11,11), and quality of life after therapy was beter for 50,76% on right leg and only for 39,51%
on left legs, were problems were biger (Figure 1) [69].
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Figure 1: Influence the lymphoedema on quality of life before and after therapy in %.
CONLUSION
Patient education concerning the possibility of lymphoedema and social supports not only the
treatment should be included in pre- and postoperative planning of gynecological cancer therapy,
with measurement too.
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Copyright  Rucigaj TP.This book chapter is open access distributed under the Creative Commons Attribution 4.0
International License, which allows users to download, copy and build upon published articles even for commercial
purposes, as long as the author and publisher are properly credited.