the adnexal mass and early ovarian cancerobgyn.med.uky.edu/sites/default/files/the adnexal...

The Adnexal Mass

The Adnexal Mass

and Early Ovarian Cancer

and Early Ovarian Cancer

Fred Ueland, MD

University of Kentucky

Gynecologic Oncology

Fred Ueland, MD

Fred Ueland, MD





“

“

Never give in. Never give

Never give in. Never give

in. Never, never, never,

in. Never, never, never,

never

never

-

-

in nothing great or

in nothing great or

small, large or petty

small, large or petty

-

-

never give in, except to

never give in, except to

convictions of honor

convictions of honor

and good sense.

and good sense.

”

”

Sir Winston Churchill

Sir Winston Churchill

Ovarian Tumors

Ovarian Tumors

Who Cares?

Who Cares?

Surgical costs exceed

Surgical costs exceed

$5,000,000,000 annually

$5,000,000,000 annually

144 million women in USA

144 million women in USA

– 5-10% will undergo a surgical

procedure for a suspected ovarian

neoplasm during their lifetime

30 million women over age 50

30 million women over age 50

–

–

17% develop cystic ovarian

17% develop cystic ovarian

tumors

tumors

–

–

2 million have persistent tumors

2 million have persistent tumors

Risk of Malignancy

Risk of Malignancy

Management challenge is an accurate risk

Management challenge is an accurate risk

of malignancy assessment.

of malignancy assessment.

Risk of malignancy within an ovarian

Risk of malignancy within an ovarian

neoplasm varies with age:

neoplasm varies with age:

–

–

10% in children

10% in children

–

–

15% in reproductive age women

15% in reproductive age women

–

–

50% in postmenopausal women

50% in postmenopausal women

Ovarian Tumors

Ovarian Tumors

Premenopausal Women

Premenopausal Women

Non

Non

-

-

inflammatory ovarian tumors

inflammatory ovarian tumors

–

–

70% functional cysts

70% functional cysts

–

–

20% neoplastic

20% neoplastic

–

–

10% endometriomas

10% endometriomas

15% of ovarian neoplasms in reproductive

15% of ovarian neoplasms in reproductive

age women are malignant

age women are malignant

Other

Other

–

–

Inflammatory process, bowel

Inflammatory process, bowel

Ovarian Tumors

Ovarian Tumors

Premenopausal Women

Premenopausal Women

Functional cysts

Functional cysts

–

–

<

<

8 cm

8 cm

–

–

Unilateral

Unilateral

–

–

Simple, unilocular on TVS

Simple, unilocular on TVS

–

–

No ascites

No ascites

Initial repeat TVS 6

Initial repeat TVS 6

-

-

8 weeks

8 weeks

OCPs do not increase likelihood of

OCPs do not increase likelihood of

resolution, but may decrease risk of

resolution, but may decrease risk of

recurrence

recurrence

Ovarian Tumors

Ovarian Tumors

Spanos W. Am J Obstet Gynecol 1973

Spanos W. Am J Obstet Gynecol 1973

0

0

0

0

Functional cysts

Functional cysts

1

1

3

3

Hydrosalpinx

Hydrosalpinx

1.4

1.4

4

4

Para

Para

-

-

ovarian cyst

ovarian cyst

10

10

28

28

Endometriosis

Endometriosis

0.3

0.3

1

1

Dysgerminoma

Dysgerminoma

1.4

1.4

4

4

Malignant epithelial

Malignant epithelial

3

3

9

9

Benign teratoma

Benign teratoma

11

11

32

32

Benign epithelial

Benign epithelial

16

16

46

46

Ovarian neoplasms

Ovarian neoplasms

28

28

81

81

Required exploratory laparotomy

Required exploratory laparotomy

72

72

205

205

Regressed under observation

Regressed under observation

%

%

# of Patients

# of Patients

Type of Cyst

Type of Cyst

Ovarian Tumors

Ovarian Tumors

Modesitt et al, Gyn Oncol 2003

Modesitt et al, Gyn Oncol 2003

Spontaneous Resolution

Spontaneous Resolution

2261

2261

(69%)

(69%)

Cyst + Septum

Cyst + Septum

537 (17%)

537 (17%)

Persistent Cyst

Persistent Cyst

220 (7%)

220 (7%)

Cyst +Solid area

Cyst +Solid area

168 (5%)

168 (5%)

Solid Mass

Solid Mass

21 (0.6%)

21 (0.6%)

Removed by unrelated surgery

Removed by unrelated surgery

40 (1.2%)

40 (1.2%)

3,259

3,259

Endometrioma

Endometrioma

Mucinous Cystadenoma

Mucinous Cystadenoma

Mature Cystic Teratoma

Mature Cystic Teratoma

Ovarian Dysgerminoma

Ovarian Dysgerminoma

Ovarian Tumors

Ovarian Tumors

Postmenopausal Women


Benign epithelial tumor

Benign epithelial tumor

Stromal tumor

Stromal tumor

–

–

Granulosa cell

Granulosa cell

–

–

Fibroma

Fibroma

–

–

Thecoma

Thecoma

Epithelial cancer

Epithelial cancer

Metastatic cancer

Metastatic cancer

Ovarian Tumors

Ovarian Tumors



50% malignant

50% malignant

Asymptomatic simple cyst < 10 cm with

Asymptomatic simple cyst < 10 cm with

normal CA

normal CA

-

-

125

125

–

–

serial TVS

serial TVS

“Any ovarian tumor in a postmenopausal

“Any ovarian tumor in a postmenopausal

woman that does not meet the above criteria

woman that does not meet the above criteria

should be assumed to be malignant”

should be assumed to be malignant”

–

–

Antiquated?

Antiquated?

Serous Ovarian Cancer

Serous Ovarian Cancer

Who Gets Referred to a Cancer

Who Gets Referred to a Cancer

Specialist?

Specialist?

Benefits of Surgical Staging?

Benefits of Surgical Staging?

Patients in whom comprehensive surgical

Patients in whom comprehensive surgical

staging confirms early

staging confirms early

-

-

stage disease have a

stage disease have a

better prognosis

better prognosis

than those who were

than those who were

thought to have early stage disease but were

thought to have early stage disease but were

unstaged

unstaged

Accurate identification of women who

Accurate identification of women who

require adjuvant chemotherapy

require adjuvant chemotherapy

Appropriate Staging

Appropriate Staging

Women with

Women with

early stage

early stage

ovarian cancer

ovarian cancer

–

–

N=291

N=291

Complete surgical staging:

Complete surgical staging:

–

–

97% gynecologic oncologists

97% gynecologic oncologists

–

–

52% general obstetrician/gynecologists

52% general obstetrician/gynecologists

–

–

35% general surgeons

35% general surgeons

McGowan L, et al. Obstet Gynecol 1985;65:568-72.

Referral Patterns

Referral Patterns

Utah Cancer Registry: 848 new ovarian cancers

Utah Cancer Registry: 848 new ovarian cancers

diagnosed 1992

diagnosed 1992

-

-

1998

1998

Only 39% were

Only 39% were

ever

ever

seen by a Gyn Onc

seen by a Gyn Onc

Patients with advanced disease had significant

Patients with advanced disease had significant

survival advantage when managed by Gyn Onc

survival advantage when managed by Gyn Onc

(median survival 26 mo vs. 15 mo, p < 0.01)

(median survival 26 mo vs. 15 mo, p < 0.01)

Age < 40, age > 70, and residence in a rural area

Age < 40, age > 70, and residence in a rural area

were not seen by a gynecologic oncologist

were not seen by a gynecologic oncologist

Carney ME, et al. Gynecol Oncol 2002;84:36

Carney ME, et al. Gynecol Oncol 2002;84:36

-

-

42.

42.

Value of Specialists

Value of Specialists

Meta

Meta

-

-

analysis (18 studies) concluded marked benefit with

analysis (18 studies) concluded marked benefit with

Gynecologic Oncologist (

Gynecologic Oncologist (

Giede

Giede

2005)

2005)

–

–

Complete surgical staging with early stage disease

Complete surgical staging with early stage disease

–

–

Optimal cytoreductive surgery with advanced disease

Optimal cytoreductive surgery with advanced disease

–

–

Improved median and overall survival

Improved median and overall survival

Others supporting GO involvement:

Others supporting GO involvement:

–

–

NCCN guidelines

NCCN guidelines

–

–

SGO, ACOG

SGO, ACOG

–

–

SOGC clinical practice guidelines

SOGC clinical practice guidelines

–

–

NIH consensus statement

NIH consensus statement

–

–

London Medical Advisory statement

London Medical Advisory statement

Suggestive of Malignancy

Suggestive of Malignancy

ACOG, SGO

ACOG, SGO

Examination

Examination

–

–

Fixed or nodular

Fixed or nodular

Imaging study

Imaging study

–

–

Mostly solid tumor or distant mets

Mostly solid tumor or distant mets

–

–

Ascites

Ascites

CA

CA

-

-

125

125

–

–

premenopausal

premenopausal

> 200

> 200

–

–

postmenopausal

postmenopausal

> 35

> 35

Im et. al. Obstet Gynecol , 2005

Im et. al. Obstet Gynecol , 2005

So How Do I Know Who Gets


Referred and Who Doesn’t?


Examination

Examination

Imaging

Imaging

Serum

Serum

Pelvic Examination

Pelvic Examination

Pelvic Examination

Pelvic Examination

Inaccuracy

Inaccuracy

Patient age

Patient age

≥

≥

55

55

–

–

30%

30%

Patient weight

Patient weight

≥

≥

200 lb

200 lb

–

–

9%

9%

Uterine weight

Uterine weight

≥

≥

200 g

200 g

–

–

16%

16%

Ueland et al, Gyn Oncol 2005






Examination

Examination

Imaging

Imaging

Serum

Serum

Pelvic Exam vs. Ultrasound

Pelvic Exam vs. Ultrasound

< 0.001

< 0.001

0.80

0.80

0.16

0.16

Uterine wt

Uterine wt

≥

≥

200 g

200 g

< 0.001

< 0.001

0.73

0.73

0.09

0.09

Patient wt

Patient wt

≥

≥

200 lb

200 lb

< 0.001

< 0.001

0.74

0.74

0.30

0.30

Patient age

Patient age

≥

≥

55

55

P value

P value

Ultrasound

Ultrasound

Pelvic Exam

Pelvic Exam



Ultrasound

Ultrasound

Differentiating Ovarian Tumors

Differentiating Ovarian Tumors

*Definition of (+) US varied with each author

56

56

41

41

81

81

98

98

12

12

442

442

Ueland, 2003

Ueland, 2003

59

59

37

37

83

83

100

100

10

10

143

143

Sassone, 1991

Sassone, 1991

73

73

74

74

92

92

82

82

22

22

180

180

Granberg, 1990

Granberg, 1990

62

62

72

72

87

87

80

80

30

30

100

100

Benacerraf, 1990

Benacerraf, 1990

75

75

88

88

95

95

62

62

36

36

102

102

Finkler, 1988

Finkler, 1988

73

73

75

75

93

93

82

82

21

21

241

241

Hermann, 1987

Hermann, 1987

39

39

31

31

73

73

70

70

15

15

406

406

Kobayashi, 1976

Kobayashi, 1976

PPV (at 20%)

PPV (at 20%)

PPV(%)

PPV(%)

Spec (%)

Spec (%)

Sens(%)

Sens(%)

Prevalence

Prevalence

Number

Number

Author

Author

Sonographic Characteristics

Sonographic Characteristics

Ovarian Tumors

Ovarian Tumors

Unilateral

Unilateral

Simple (MI < 5)

Simple (MI < 5)

Doppler

Doppler

–

–

PI > 1.0, RI > 0.4

PI > 1.0, RI > 0.4

–

–

Peripheral flow

Peripheral flow

No ascites

No ascites

Resolution

Resolution

Bilateral

Bilateral

Complex (MI

Complex (MI

≥

≥

5)

5)

–

–

Partly solid

Partly solid

–

–

Internal papillations

Internal papillations

Doppler

Doppler

–

–

PI < 1.0, RI < 0.4

PI < 1.0, RI < 0.4

–

–

Central flow

Central flow

Ascites

Ascites

Persistence or growth

Persistence or growth

Benign

Benign

Malignant

Malignant

Kentucky Morphology Index


Ueland et al Gyn Oncol 2003

Ueland et al Gyn Oncol 2003

UK gynecologic

UK gynecologic

ultrasound database

ultrasound database

442 women with

442 women with

confirmed ovarian

confirmed ovarian

tumor

tumor

–

–

Morphology Indexing

Morphology Indexing

–

–

Color Flow Doppler

Color Flow Doppler

–

–

Surgery

Surgery

Tumor Structure

Tumor Structure

Score = 0

Score = 0

Tumor Structure

Tumor Structure

Score = 3

Score = 3

Tumor Structure

Tumor Structure

Score = 5

Score = 5

Morphology Index

Morphology Index

Total Score (0

Total Score (0

-

-

4)

4)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4

% Benign

% Cancer

Morphology Index

Morphology Index

Total Score (5

Total Score (5

-

-

10)

10)

0

10

20

30

40

50

60

70

80

90

100

5 6 7 8 9 10

% Benign

% Cancer

20

32

38

92

77

83



MI

MI

< 5

< 5

benign

benign

MI

MI

≥

≥

5

5

malignant

malignant



Sensitivity

Sensitivity

0.981

0.981

Specificity

Specificity

0.807

0.807

Positive predictive value

Positive predictive value

0.409

0.409

Negative predictive value

Negative predictive value

0.997

0.997

Accuracy

Accuracy

0.828

0.828

Disease Prevalence = 12%

Disease Prevalence = 12%

What about Doppler?

What about Doppler?

Doppler

Doppler

0.997

0.997

0.409

0.409

0.807

0.807

0.981

0.981

MI

MI

0.854

0.854

0.056

0.056

0.640

0.640

0.163

0.163

No flow

No flow

0.867

0.867

0.222

0.222

0.867

0.867

0.222

0.222

RI < 0.4

RI < 0.4

0.905

0.905

0.288

0.288

0.776

0.776

0.528

0.528

PI < 1.00

PI < 1.00

NPV

NPV

PPV

PPV

Spec

Spec

Sens

Sens

θ

θ

f

f

0

0

= transmitted US frequency

= transmitted US frequency

v cos

v cos

θ

θ

= target velocity

= target velocity

TVS probe

TVS probe

c

c

= velocity of surrounding medium

= velocity of surrounding medium

vessel

vessel

∆

∆

f = 2f

f = 2f

0

0

v (cos

v (cos

θ

θ

) / c

) / c

Doppler Reproducibility

Doppler Reproducibility

∆

∆

f = 2f

f = 2f

0

0

v (cos

v (cos

θ

θ

) / c

) / c

Is the angle of insonation constant (

Is the angle of insonation constant (

θ

θ

)?

)?

–

–

2 to 3 fold change for

2 to 3 fold change for

∆

∆

θ

θ

(from 30

(from 30

°

°

-

-

80

80

°

°

)*

)*

–

–

Optimal angle and frequency depends on depth

Optimal angle and frequency depends on depth

of vessel

of vessel

Is each Doppler measurement of the same

Is each Doppler measurement of the same

vessel? Are these vessels straight?

vessel? Are these vessels straight?

*J Vasc Surg 1990; 11:688

*J Vasc Surg 1990; 11:688

-

-

94

94

Ultrasound Conclusions

Ultrasound Conclusions

1.

1.

MI

MI

≥

≥

5

5

40% malignant

40% malignant

2.

2.

MI < 5

MI < 5

0.3% malignant

0.3% malignant

3.

3.

Doppler adds little

Doppler adds little

Other Imaging

Other Imaging

CT scan abdomen and pelvis

CT scan abdomen and pelvis

–

–

IV and PO contrast

IV and PO contrast

–

–

CT

CT

-

-

guided biopsy

guided biopsy

Accuracy exceeds 90% for solid tumors

Accuracy exceeds 90% for solid tumors

What about high risk cystic tumors?

What about high risk cystic tumors?

MRI

MRI

PET

PET

CT Scan

CT Scan

Omental cake

Ovarian tumor





Examination

Examination

Imaging

Imaging

Serum

Serum

CA

CA

-

-

125

125

Antigen derived from:

Antigen derived from:

–

–

coelomic

coelomic

epithelium (pericardium, pleura, peritoneum)

epithelium (pericardium, pleura, peritoneum)

–

–

mullerian

mullerian

epithelium (tubal, endometrial,

epithelium (tubal, endometrial,

endocervical

endocervical

)

)

Two different assays

Two different assays

–

–

Assay I

Assay I

<

<

35 U/ml

35 U/ml

–

–

Assay II < 20 U/ml

Assay II < 20 U/ml

Expressed by 80% non

Expressed by 80% non

-

-

mucinous EOC

mucinous EOC

FDA

FDA

-

-

approved to follow the progress of cancer treatment

approved to follow the progress of cancer treatment

–

–

Neither a screening nor a diagnostic test

Neither a screening nor a diagnostic test

Normal CA

Normal CA

-

-

125 values (low sensitivity)

125 values (low sensitivity)

–

–

50% of early stage ovarian cancers

50% of early stage ovarian cancers

–

–

20

20

-

-

25% of advanced stage ovarian cancers

25% of advanced stage ovarian cancers

–

–

Mixed mullerian tumors, clear cell cancers

Mixed mullerian tumors, clear cell cancers

CA

CA

-

-

125

125

Non

Non

-

-

specific

specific

Benign ovarian cysts

Benign ovarian cysts

Uterine leiomyomata

Uterine leiomyomata

Pelvic inflammatory

Pelvic inflammatory

disease

disease

Endometriosis

Endometriosis

Adenomyosis

Adenomyosis

Pregnancy

Pregnancy

Menstruation

Menstruation

Ascites

Ascites

Heart failure

Heart failure

Liver failure

Liver failure

Renal failure

Renal failure

Peritoneal tuberculosis

Peritoneal tuberculosis

Diverticulitis

Diverticulitis

Pancreatitis

Pancreatitis

Recent abdominal or

Recent abdominal or

thoracic surgery

thoracic surgery

Other malignancies

Other malignancies

So Again, What Should I Do?

So Again, What Should I Do?

Surgical removal of ovarian

Surgical removal of ovarian

tumor if symptomatic or

tumor if symptomatic or

high risk

high risk

imaging

imaging

Sonographic

Sonographic

observation if

observation if

asymptomatic, low risk MI

asymptomatic, low risk MI

–

–

6 wks, 3 mo, 6 mo

6 wks, 3 mo, 6 mo

CT scan abdomen/pelvis if

CT scan abdomen/pelvis if

suspect malignancy

suspect malignancy

High Risk Indicators

High Risk Indicators

Ultrasound

Ultrasound

(Ueland et al, 2003; Sassone et al, 1991)

(Ueland et al, 2003; Sassone et al, 1991)

–

–

Internal papillary projection

Internal papillary projection

–

–

Cystic and solid, solid


–

–

Ascites

Ascites

CT Scan/MRI

CT Scan/MRI

(Kurtz et al 1999)

(Kurtz et al 1999)

–

–



–

–

Ascites

Ascites

CA

CA

-

-

125

125

(Roman et al, 1997)

(Roman et al, 1997)

–

–

Premenopausal >100 U/mL

Premenopausal >100 U/mL

–

–

Postmenopausal >35 U/mL

Postmenopausal >35 U/mL

Laparoscopy

Laparoscopy

Ovarian Tumor

Ovarian Tumor

Laparoscopy

Laparoscopy

Guidelines

Guidelines

Prepared for laparotomy

Prepared for laparotomy

–

–

Informed consent

Informed consent

Surgical technique

Surgical technique

–

–

Abdominopelvic inspection, biopsy

Abdominopelvic inspection, biopsy

–

–

Washings

Washings

–

–

Tumor removal and containment with endoscopic bag

Tumor removal and containment with endoscopic bag

–

–

No morcellation, please

No morcellation, please

–

–

Intraoperative frozen section

Intraoperative frozen section

Principles

Principles

Ovarian Tumor

Ovarian Tumor

Laparoscopy

Laparoscopy

Be principled

Be principled

–

–

Do not delay treatment to “confirm diagnosis” at

Do not delay treatment to “confirm diagnosis” at

laparoscopy

laparoscopy

–

–

For high risk tumor, consider referral to specialist

For high risk tumor, consider referral to specialist

–

–

Informed consent for surgery includes explanation of

Informed consent for surgery includes explanation of

alternatives

alternatives

–

–

“What would I do for my mother?”

“What would I do for my mother?”

Ovarian Cancer

Ovarian Cancer

Incidence and Mortality

Incidence and Mortality

Data from the

Data from the

American Cancer

American Cancer

Society

Society

200 Kentucky deaths from ovarian cancer in 2006

200 Kentucky deaths from ovarian cancer in 2006

Stage and Outcome

Stage and Outcome

50%

50%

Overall

Overall

0

0

-

-

20%

20%

15

15

IV

IV

15

15

-

-

30%

30%

55

55

III

III

65%

65%

6

6

II

II

95%

95%

24

24

I

I

Survival

Survival

Percent

Percent

Stage

Stage

American

American Cancer Society

Ovarian Cancer

Ovarian Cancer

Symptoms

Symptoms

Survey distributed to 1500 women who

Survey distributed to 1500 women who

subscribe to

subscribe to

CONVERSATIONS!,

CONVERSATIONS!,

a

a

newsletter about ovarian carcinoma

newsletter about ovarian carcinoma

1725 surveys returned

1725 surveys returned

Median age 52 years

Median age 52 years

70% had stage III or IV disease

70% had stage III or IV disease

Goff, B, et al. Cancer 2000;89:2068

Goff, B, et al. Cancer 2000;89:2068

-

-

75.

75.

Ovarian Cancer

Ovarian Cancer

Symptoms

Symptoms

95% of patients reported having symptoms

95% of patients reported having symptoms

prior to diagnosis

prior to diagnosis

–

–

Abdominal 77%

Abdominal 77%

–

–

Gastrointestinal 70%

Gastrointestinal 70%

–

–

Pain 58%

Pain 58%

–

–

Constitutional 50%

Constitutional 50%

–

–

Urinary 34%

Urinary 34%

–

–

Pelvic 26%

Pelvic 26%

Ovarian Cancer

Ovarian Cancer

Symptoms

Symptoms

Asymptomatic prior to diagnosis

Asymptomatic prior to diagnosis

–

–

Stage I/II

Stage I/II

–

–

11%

11%

–

–

Stage III/IV

Stage III/IV

–

–

3%

3%

Women who ignored their symptoms were

Women who ignored their symptoms were

more likely to be diagnosed with advanced

more likely to be diagnosed with advanced

stage disease

stage disease

Ovarian Cancer

Ovarian Cancer

Symptoms

Symptoms

Factors associated with delay in diagnosis

Factors associated with delay in diagnosis

–

–

Omission of pelvic exam at first visit

Omission of pelvic exam at first visit

–

–

Multiple symptoms

Multiple symptoms

–

–

Missed diagnosis: no problem, depression, stress, IBS, or

Missed diagnosis: no problem, depression, stress, IBS, or

gastritis

gastritis

–

–

No imaging or CA

No imaging or CA

-

-

125

125

–

–

Younger age

Younger age

Type of health care provider seen initially, insurance,

Type of health care provider seen initially, insurance,

and specific symptoms did not correlate with a delay

and specific symptoms did not correlate with a delay

in diagnosis

in diagnosis

Cancer History

Cancer History

Ovarian cancer

Ovarian cancer

Breast cancer

Breast cancer

Endometrial cancer

Endometrial cancer

Other

Other

BRCA 1,2

BRCA 1,2

HNPCC

HNPCC

Conclusions

Conclusions

Identify patients at risk

Identify patients at risk

–

–

Cancer history, symptoms, other

Cancer history, symptoms, other

Ovarian examination is often inaccurate

Ovarian examination is often inaccurate

–

–

Age, obesity, large uterus

Age, obesity, large uterus

Stratify risk with ultrasound, other imaging

Stratify risk with ultrasound, other imaging

Informed surgical consent

Informed surgical consent

Consider laparoscopic approach if feasible

Consider laparoscopic approach if feasible

Conclusions

Conclusions

Referral for an adnexal tumor depends on

Referral for an adnexal tumor depends on

risk of malignancy assessment

risk of malignancy assessment

When a Gyn Onc performs surgery for

When a Gyn Onc performs surgery for

early stage ovarian cancer, patients are more

early stage ovarian cancer, patients are more

likely to be accurately staged and receive

likely to be accurately staged and receive

proper adjuvant treatment

proper adjuvant treatment

"Let us have faith that right makes might, and

"Let us have faith that right makes might, and

in that faith, let us, to the end, dare to do

in that faith, let us, to the end, dare to do

our duty as we understand it."

our duty as we understand it."

Lincoln's Cooper Institute Address

Lincoln's Cooper Institute Address

February 27, 1860.

February 27, 1860.

the adnexal mass and early ovarian cancerobgyn.med.uky.edu/sites/default/files/the adnexal...

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