Expert answer:Prophylactic Hysterectomy
Expert answer:For this assignment, read the article, which I sent to you, you will review and reflect on the Prophylactic Hysterectomy article. This article can be applied to healthcare providers in the primary care and specialty settings. Discussion of the article is based on the course objectives and weekly content, which emphasize the core learning objectives for an evidence-based primary care curriculum. Throughout your nurse practitioner program, discussions are used to promote the development of clinical reasoning through the use of ongoing assessments and diagnostic skills, and to develop patient care plans that are grounded in the latest clinical guidelines and evidence-based practice. APA format with at least 5 references, plus the article no older than 5 years old. Discuss any “take-away” thoughts from the article.What are the ethical dilemmas to consider with prophylactic surgeries?Discuss the screeningsInterventionsOptionsEducation that you would provide to a patient that has a strong family history of ovarian cancer. What if the patient has no health insurance? What resources could you offer to assist the patient?Discuss and describe what causing patient to undergo a Prophylactic Hysterectomy.
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Gynecologic Oncology 102 (2006) 475 – 479
www.elsevier.com/locate/ygyno
Role of prophylactic hysterectomy in patients
at high risk for hereditary cancers
Jeannine A. Villella a , Madhu Parmar a , Kathleen Donohue b ,
Cathy Fahey c , M. Steven Piver c , Kerry Rodabaugh a,⁎
a
Department of Gynecologic Oncology, Buffalo, NY 14263, USA
Department of Health Behavior, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
Gilda Radner Familial Ovarian Cancer Registry, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
b
c
Received 23 September 2005
Available online 13 February 2006
Abstract
Background. Current surgical recommendations for ovarian cancer prophylaxis in women at high risk of developing ovarian cancer include
bilateral salpingo-oophorectomy (risk-reducing salpingo-oophorectomy (RRSO)). The role of hysterectomy is unclear. We sought to determine
outcomes following prophylactic surgery in high-risk women.
Methods. We surveyed unaffected members of the Gilda Radner Familial Ovarian Cancer Registry who had undergone oophorectomy from
1981 to 2002. Data were collected and analyzed for statistical significance by the Fisher’s Exact Test.
Results. Two hundred eighty women were surveyed, and 154 (55%) responded; 97% were Caucasian and 14% reported being Jewish. The
median age of the respondents was 51 years (range 29–79); median age at oophorectomy was 41 years (range 15–68). Fifty-eight patients (38%)
reported a laparoscopic procedure. One hundred five patients (68%) had a simultaneous hysterectomy, and 4 (3%) had a prior hysterectomy. Fortyfour patients (29%) underwent BSO only. Of these 44 patients, 40 (91%) did not require a subsequent hysterectomy. Of the 4 who did, 2 were for
leiomyomas, one for menorrhagia and the other was unknown. While not statistically significant, of the 3 patients who developed a subsequent
gynecologic malignancy, all had undergone a hysterectomy. There was a statistically significant difference in whether or not the uterus was
removed as part of the procedure by time period, whereby women treated prior to 1990 had a higher likelihood of having a hysterectomy
(P = 0.03).
Conclusion. The women in our study did not require hysterectomy for prevention of malignancy. We conclude that one should screen for
benign gynecological indications for hysterectomy when planning a prophylactic BSO for prevention of ovarian cancer. Other potential risk
factors for endometrial cancer, including the role of UPSC in HBOC, remain to be elucidated.
© 2006 Elsevier Inc. All rights reserved.
Keywords: Familial ovarian cancer; Prophylactic oophorectomy; Hysterectomy
Introduction
The lifetime risk of developing ovarian cancer in the general
population is 1–2%. For women with a family history of
ovarian cancer, their lifetime risk of developing this disease
increases to 4 to 5% with one first degree relative and to 7%
when 2 first-degree relatives are affected [1,2]. The lifetime risk
of ovarian cancer in women belonging to HBOC (Hereditary
⁎ Corresponding author.
E-mail address: Kerry.rodabaugh@roswellpark.org (K. Rodabaugh).
0090-8258/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.ygyno.2006.01.006
Breast and Ovarian Cancer Syndrome) families is 40–60% [3].
Increased awareness of a genetic component to this disease has
led to formation of ovarian cancer registries [4]. Registries and
clinics specific to hereditary ovarian cancer syndromes have
been the source of high-risk patient cohorts used to test riskreducing strategies. These strategies include increased surveillance (bimanual pelvic exams, pelvic ultrasound with color flow
Doppler and serial serum CA-125 levels), oral contraceptive
pills and risk-reducing salpingo-oophorectomy (RRSO). The
National Institute of Health consensus statement states that the
risk of ovarian cancer in women from families with HBOC
476
J.A. Villella et al. / Gynecologic Oncology 102 (2006) 475–479
syndromes is sufficiently high to recommend RRSO in women
at age 35 or after childbearing is completed [5,6]. These
recommendations additionally advise that women undergoing
RRSO should be informed that removal of the tubes and ovaries
does not provide 100% protection and that they remain at risk of
primary peritoneal carcinoma [7].
Current recommendations for risk reduction include prophylactic bilateral salpingo-oophorectomy in women at high
risk for developing ovarian cancer [8]. Controversy regarding
the recommendations for the type of prophylactic surgery
offered women arises with the question “is hysterectomy a
necessary component of the prophylactic surgery?” Proponents
argue that it reduces incidence of future gynecologic surgery,
risk of fallopian tube cancer and risk of papillary serous
carcinoma of the uterus and simplifies hormone replacement
therapy. Those in opposition counter that it increases morbidity,
operative time, hospital stay, recovery time and overall costs.
Our objective in this study was to evaluate actual practice
patterns in women at risk who had undergone RRSO. We also
sought to determine the outcome of those women who did not
have hysterectomy as part of their initial procedure.
Materials and methods
This study invited participation, via questionnaire, of 280 women in the
Gilda Radner Familial Ovarian Cancer Registry (GRFOCR) who had undergone
previous oophorectomy from 1981 to 2002. Inclusion in the Registry requires a
family history of ovarian cancer and the majority of women had at least 2 close
(1st or 2nd degree) relatives with ovarian cancer. In addition to demographic
information, indications for hysterectomy, incidence of hysterectomy and the
incidence of subsequent gynecological cancers following prophylactic surgery
were collected. The Registry routinely pursues the pathology report and medical
records of all reported malignancies to confirm diagnoses. If there was no cancer
history, this was not performed.
Categorical data were analyzed using Fisher’s Exact Test. Patients were
stratified based on whether or not a hysterectomy was performed coincident with
the oophorectomy. Comparisons were made between these two patient subsets
for proportions of subsequent gynecologic malignancy (yes or no), surgery type
for complications (bowel obstruction, bowel resection, colon resection or
exploratory) and era of diagnosis (in 5-year intervals). The null hypothesis in
each of these comparisons was that there were equal proportions between the
two patient subsets for each level of the variable of interest. The two-sided
alternative hypothesis was that the proportion in one patient subset was much
larger or smaller than in the other subset. Statistical significance was defined to
be a P value b0.05. Data analysis was performed using the StatXact5 software
package. Ninety-five percent confidence intervals are stated where appropriate.
Results
A total of 154 (55%) women responded to the one time
mailing of the survey. The median age of the women completing
the survey was 51 years (range: 29–79 years). The majority of
Table 1
Mutation likelihood risk assessment
Shattuck-Eidens (BRCA1 only)
Couch (BRCA1 only)
BRCAPRO
Myriad
Average
Low
High
22%
25%
21%
16%
0.4%
0.3%
0.1%
3%
99%
96%
100%
90%
Table 2
Characteristics of oophorectomy procedure (n = 154)
Characteristic
Ovaries removed
One
Both
Unknown
Uterus removed
Yes
Yes (prior)
No
Unknown
Type of surgery
Laparotomy
Laparoscopy
Vaginal
Unknown
Age at oophorectomy (years)
Median
Range
No. (%)
10 (6%)
143 (93%)
1 (1%)
105 (68%)
4 (3%)
44 (29%)
1 (1%)
88 (57%)
58 (38%)
2 (1%)
6 (4%)
41
(15, 68)
the women were white (97%), three were Hispanic (2%) and
one Native American (1%). Christianity was the most common
religion as self reported by 127 women (82%) followed by 21
(14%) who were Jewish and 6 (4%) who were either other
religions or unreported religion. Patients were examined by a
gynecologist frequently, with 123 (80%) having at least annual
pelvic examinations. One hundred and six (69%) patients had a
history of oral contraceptive use, and 141 (92%) had a history of
a full term pregnancy.
Because BRCA mutation status was unavailable for these
patients, four risk models or databases (BRCAPRO, ShattuckEidens, Couch and Myriad laboratory data tables) were used for
calculating BRCA1 and BRCA2 mutation likelihood to help
assess the patients’ risk for developing ovarian cancer. Eightysix percent had a BRCA1 or BRCA2 mutation likelihood of
7.8% or greater as calculated by at least one of these models
(compared to a general population risk of b1%). Using the
BRCAPRO model, the average patient in this study had a 21%
risk of harboring a mutation in the BRCA1 or 2 genes. This
highlights the high risk status of patients enrolled in this study.
Table 1 compares the four models.
The characteristics of the oophorectomy procedure are
summarized in Table 2. The median patient age at the time of
oophorectomy was 41 years (range: 15–68 years). There were a
total of 109 women (71%) who had their uterus removed,
including four women whose uterus had been removed
previously. Forty-four women (29%) did not have their uterus
removed at the time of oophorectomy. Types of surgical
procedures included laparotomy (57%), laparoscopy (38%),
vaginal (1%) and unknown (4%).
Table 3 documents the incidence of hysterectomy following
RRSO. Among the 47 women who did not report prior
hysterectomy, 40 (91%, CI: 78%, 97%) had not undergone
subsequent hysterectomy at the time of the survey. Four women
(9%, CI: 2%, 22%) did have a subsequent hysterectomy, two
secondary to uterine myomas, one due to menorraghia and one
woman whose reason was unreported. There were 3 women
(6%) whose hysterectomy status was unknown.
J.A. Villella et al. / Gynecologic Oncology 102 (2006) 475–479
Table 3
Incidence of hysterectomy following risk-reducing salpingo-oophorectomy
(n = 44)
Incidence
No. (%)
No
Yes
Reason
Uterine myomas
Menorraghia
Unknown
40 (91%)
4 (9%)
2
1
1
Table 4 details the incidence of subsequent gynecologic
malignancy, stratified by whether or not the patients received a
hysterectomy at the time of oophorectomy. There were no
subsequent malignancies identified among those who did not
have their uterus removed. In the group of women who had a
hysterectomy as part of their prophylactic procedure, 3 (3%)
had a subsequent gynecologic malignancy: two peritoneal
cancers and one recurrent ovarian carcinoma in a woman who
was diagnosed with ovarian cancer at her original surgery.
These differences were not statistically significant (two-sided P
value = 0.56, Fisher’s Exact Test).
Forty-eight women underwent some type of subsequent
surgery, mostly for procedures unrelated to the oophorectomy.
A total of five women had surgery for bowel obstruction or
bowel resection, and four women reported undergoing subsequent exploratory surgery. These data were stratified by whether
or not the women had a hysterectomy at the time of the
oophorectomy procedure, and there were no statistically
significant differences between the two subsets of patients (P
value = 0.72, two-sided Fisher’s Exact Test).
In stratifying, by 5-year intervals of when the patients
received their RRSO, whether or not the women received a
hysterectomy at the time of the procedure, we found the
following: among the women who retained their uterus, the vast
majority (91%) had been treated in 1990 or later: 9 (20%)
1990–1994, 17 (39%) 1995–1999, 14 (32%) 2000–2003.
Among those who underwent a hysterectomy, 72% were treated
during the same time period: 34 (32%) 1990–1994, 21 (20%)
1995–1999, 21 (20%) 2000–2003. Twenty-five percent of the
women who had a hysterectomy at the time of oophorectomy
were treated prior to 1990, while among the women who did not
undergo a hysterectomy; only 9% were treated prior to 1990.
Comparing the women for whom the time period of the
oophorectomy procedure was known (n = 146), there was a
statistically significant difference in whether or not the uterus
was removed as part of the procedure, comparing prior to 1990
versus 1990 or later. A significantly greater percentage of
women had their uterus removed prior to 1990 (P value = 0.03,
two-sided Fisher’s Exact Test).
Discussion
One of the challenges facing those who care for women at
increased risk for breast or ovarian cancer is the identification of
strategies that may be used to reduce cancer risks or mortality.
Health care providers are faced with multiple options, including
477
increased surveillance, chemoprevention and risk-reducing
surgery. Much of the evidenced-based medicine regarding
these options is retrospective. Given the lack of prospective
standardized studies, clinicians search for the most effective
strategies to care for these at-risk patients. Carriers of inherited
mutations in the BRCA genes are thought to have a lifetime risk
of developing breast and ovarian cancer of 50–85% and 20–
40% respectively [9,10]. Women who carry germ line mutations
in the BRCA1 or BRCA2 genes may choose to undergo
prophylactic oophorectomy to decrease their risk of developing
ovarian and breast carcinomas [11,12].
The extent of surgery remains subject to debate. Some
authors believe that adding hysterectomy at the time of BSO
will prevent the need for future gynecologic surgery, either for
benign or malignant reasons. Hysterectomy at the time of RRSO
has been recommended by some investigators because it
decreases the risk of endometrial cancer in patients using
Tamoxifen for breast cancer [13]. Patients suffering from
menopausal symptoms following RRSO are also at risk for
osteoporosis and may choose to take estrogens. If the uterus is
present, combination hormone replacement therapy is warranted for the prevention of endometrial cancer. Recently, it has
been shown that this combination therapy may increase breast
cancer, pulmonary embolism and stroke incidence [14].
Hysterectomy at the time of RRSO can simplify hormone
replacement and may decrease these risks.
An additional argument in favor of hysterectomy at the time
of RRSO is the potential prevention of fallopian tube
carcinoma. Although the surface area of the fallopian tube is
much greater than that of the ovary, the ovary gives rise to
malignancy more than 20 times as frequently [15], and primary
fallopian tube carcinoma is a rare entity. While about 11% of
fallopian tube cancers present with the symptom triad of
leukorrhea, pelvic mass and pain [16], the majority are
asymptomatic. During the last several years, evidence of a
relationship between carcinoma of the fallopian tube and
mutations in BRCA1 or 2 genes has emerged. Initial reports
were from case studies, and now newer epidemiologic evidence
has focused on retrospective BRCA testing on fallopian tube
cancers [17]. The Ontario Cancer Registry had 44 patients
diagnosed with fallopian tube carcinoma from 1990 to 1998.
Five of the 44 cases were positive for a BRCA1 mutation (11%)
and two for a BRCA2 mutation (5%) [18]. Three of these
patients were of Ashkenazi Jewish descent, and only 2 carried a
founder mutation. Lu et al. reviewed 50 women at high risk for
ovarian cancer who underwent RRSO. Out of 33 whom had a
greater than 25% calculated risk of carrying a germ line
Table 4
Incidence of subsequent gynecologic malignancy by initial hysterectomy status
Initial
hysterectomy
Subsequent gynecologic malignancy (P = 0.56)
Yes
No
Total
Yes
No
Unknown
Total
3
0
–
3
103
43
–
146
106
43
5
154
478
J.A. Villella et al. / Gynecologic Oncology 102 (2006) 475–479
mutation in either the BRCA1 or BRCA2 gene, serial sections of
the ovaries and fallopian tubes revealed 3 occult carcinomas,
one of which was of the fallopian tube [11]. Another
histological review of 30 women who were BRCA mutation
carriers and underwent an RRSO found 4 occult fallopian tube
carcinomas [19].
Carcinoma of the fallopian tube is believed to be part of the
clinical spectrum of BRCA-associated gynecologic malignancies. While the additional morbidity of adding a hysterectomy to
the RRSO is minimal [18,20], we do not believe it is necessary
to prevent future malignancies of the fallopian tube. There have
been no documented cases of fallopian tube cancer arising in the
cornua of a patient who had a prophylactic oophorectomy
without hysterectomy. The most common sites of fallopian tube
carcinomas are in the ampulla followed by the infundibulum
[21–23]. The need for hysterectomy to prevent fallopian tube
carcinoma, therefore, remains debatable.
In considering the risks of uterine pathology in patients
harboring a BRCA mutation, a retrospective cohort of 199
Ashkenazi Jewish women with endometrial cancer revealed
only 3 (1.5%) tumors associated with BRCA1 mutation, an odds
ratio of 0.75 (CI 0.24, 2.34; P = 0.6). Thus, a mutation in BRCA
may not confer an increased lifetime risk of endometrial cancer
[24]. The biologic mechanisms of uterine papillary serous
carcinoma (UPSC) are largely unknown. Case reports have lead
to further investigations as to the role of BRCA mutations in
UPSC. One report documented an Ashkenazi Jewish woman
with UPSC and her sister with papillary serous carcinoma of the
ovary. Both had a germ line BRCA1 mutation (5382insC),
suggesting a possible genetic link between BRCA1 mutations
and UPSC [25]. An investigation of an Ashkenazi Jewish family
with UPSC reported no identified BRCA1 or BRCA2 mutations
[26]. Another study retrospectively screened 56 women with
UPSC, none of whom was Ashkenazi Jewish, using a protein
truncation assay believed to identify 70% of mutations occurring
in the coding region of the BRCA genes. These samples were
also tested for the three most common Ashkenazi Jewish founder
mutations known to occur in the BRCA genes. No mutations
were discovered, and the authors concluded that UPSC was not a
likely manifestation of the HBOC syndrome [27]. Other groups
studying UPSC patients found that 4 out of 20 Ashkenazi Jewish
women had BRCA1 mutations [28] and 3 out of 9 Ashkenazi
Jewish women had BRCA2 mutations. The current data suggest
that Ashkenazi Jewish women with BRCA mutations may be at
risk for UPSC, and therefore this subgroup of patients might
benefit from prophylactic hysterectomy [27,28].
Conclusions
Our study found that 9% of the women surveyed required
subsequent hysterectomy following their RRSO procedure.
Interestingly, among the women known to have a uterus at the
time of surgery (n = 149), 70% had their uterus removed at the
time of oophorectomy, and only 30% did not. Moreover, among
the women whose uterus was not removed, there were no
subsequent gynecologic malignancies identified, although not
statistically significant. Because only a small number of patients
developed a subsequent gynecologic malignancy (n = 3), these
results must be considered anecdotal. There was not a difference
in incidence of subsequent bowel, colon or exploratory surgery
between these two groups of women. There was, however, a
significant difference in hysterectomy being part of the
oophorectomy procedure based on the time period when the
surgery was performed, whereby women treated prior to 1990
were much more likely to have received a hysterectomy. This
may be related to the fact that the American College of
Obstetricians and Gynecologists issued guidelines on RRSO in
1994.
While our study is limited by size and the retrospective nature
of the survey, we are able to conclude that, while women do not
require hysterectomy for prophylaxis of ovarian or fallopian tube
cancer, they should be screened for benign gynecological
indications for hysterectomy. Furthermore, serial sectioning of
these specimens is imperative for complete evaluation and
identification of those patients who may harbor occult
malignancies and thus will need a full staging procedure and
possibly adjuvant treatment [29–32]. Another possible limitation to our study may be that, although all of the patients in the
study had extensive pedigree ana …
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