Diseases of the Ovary and Fallopian Tube

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Chapter 13 Diseases of the Ovary and Fallopian Tube

Clinical Features of Ovarian Tumours 252

Symptoms Due to Size 252

Pressure Symptoms 252

Ovarian Cyst Accidents 259

Complications of Ovarian Tumours 259

Clinical Features 259

Differential Diagnosis 259

Management 259

Rupture of Ovarian Cyst 260

Benign and Malignant Ovarian Tumours 262

Clinical Features 262

Investigation 262

Histological Classification 263

Risk Factors for Ovarian Cancer 264

Carcinoma of the Ovary 264

Ovarian Cancer Risk Factors 264

Epithelial Ovarian Tumours 265

Serous Cystadenoma 265

Serous Cystadenocarcinoma 265

Mucinous Cystadenoma 266

Mucinous Cystadenocarcinoma 266

Germ Cell Ovarian Tumours 267

Clinical Features 267

Treatment 267

Germ Cell Ovarian Tumours – Undifferentiated 268

Teratomata 269

Other Ovarian Tumours 270

Hormone-Producing Tumours 271

Oestrogen-Producing Tumours 272

Fibroma 272

Androgen-Producing Tumours 273

Other Hormone-Producing Tumours 275

Carcinoid (Serotonin-Producing Tumour) 275

Struma Ovarii (Thyroid Type Tumour) 275

Choriocarcinoma of the Ovary 275

Hormone Production by Non-Functioning Tumours 275

Surgical Treatment of Ovarian Tumours 276

Treatment of Ovarian Cancer 277

Spread of Ovarian Cancer 277

Incision 278

Inspection 278

Organs Removed 278

Cytology 278

Staging of Ovarian Cancer 279

Principles of Chemotherapy 281

Malignant Tumour Growth 281

Mode of Chemotherapeutic Action 281

Chemotherapeutic Agents in Ovarian Cancer 282

Chemotherapy Toxicity 282

Present Prognosis for Invasive Epithelial Ovarian Cancer 282

Broad Ligament Cysts 283

Broad Ligament Cysts (Parovarian Cysts) 283

Diagnosis 284

Operation 284

Cysts of Kobelt’s Tubules, Hydatids of Morgagni, Fimbrial Cysts 284

Carcinoma of Fallopian Tubes 285

Pathology 285

Clinical Features 285

Clinical Staging 285

Treatment 285

Clinical features of ovarian tumours

Symptoms due to size

Ovarian tumours are often large by the time the doctor is consulted because of the lack of any specific symptoms. Menstrual function is usually normal, and any irregularity is attributed to perimenopausal change. The patient may have noticed that her clothes are getting tight and have attributed this to weight gain or, if the abdominal swelling has coincided with amenorrhoea, she may believe herself to be pregnant.

Pressure symptoms

There are commonly increased frequency of micturition, gastrointestinal symptoms and a dull pain in the lower abdomen. Very large tumours may cause shortness of breath, peripheral oedema or varicosities in the legs.

Small tumours remain in the pelvis and will only be detected on bimanual examination or by ultrasound.

Larger tumours fill the pelvis and usually lie between the uterus and the sacrum. If the patient is not too obese, the uterus can be distinguished on palpation as separate from the tumour.

A tumour occupying the abdomen causes a midline swelling and is usually tense.

Little can be done at this stage to classify the tumour or exclude a malignancy. Further information can be gained by undertaking imaging and tumour marker assessment including CA125 and CEA (AFP, and B-HCG are included in younger patients).

If the patient is very thin, irregularities may be palpated and sometimes two tumours may be suspected.

Some tumours of moderate size may have a long pedicle composed of the attenuated broad ligament and the fallopian tube, which allows the tumour to be displaced from side to side or to occupy a high abdominal position. Such cysts are at increased risk of torsion.

The upper pole can usually be distinguished and the lower pole can be palpated per vaginam. Adhesions, inflammation and displacement of pelvic organs may all exist along with a tumour, making examination difficult.

Differential diagnosis

An experienced examiner will recognise an ovarian tumour mainly because ovarian tumour is, in the circumstances, the most likely diagnosis. All abdominal swellings should be subjected to further imaging with a combination that may include ultrasound, computerised tomography (CT) and magnetic resonance imaging (MRI) scan examination.

Two very obvious mistakes must be avoided.

1. The midline swelling due to a full bladder.

2. The 16-week pregnancy. The gravid uterus at this stage has a very soft isthmic region, which can resemble the pedicle of a cyst.

Ascites

A fluid thrill may be elicited from an ovarian cyst, and ascites and tumour may coexist; but as a rule, the distinction should be easily made. The presence of ascites raises the suspicion of cancer.

(See ‘Shifting dullness’, page 77.)

With ascites

The bowel floats on the fluid. The percussion note is resonant over the top of the swellings and dull over the flanks.

With ovarian cyst

Percussion note is dull over the top of the swelling and resonant in the flanks.

Uterine fibroids

A large midline intramural fibroid may be indistinguishable from a solid ovarian tumour until the abdomen is opened and an entirely different surgical problem encountered.

An ovarian tumour will displace the uterus forwards or downwards where it may, sometimes, be identified on vaginal examination.

An intramural fibroid will obscure the uterus. The cavity is often elongated.

Ultrasound examination should be able to distinguish between a fibroid and an ovarian cyst; but many ovarian tumours are solid, and some fibroids undergo cystic degeneration. Vaginal ultrasound gives a more detailed picture of the pelvic contents and a more precise diagnosis.

Pelvic inflammation

The swelling palpated per vaginam may be due to an adherent mass of the uterus, the tubes, ‘chocolate’ ovarian cysts, and the bowel.

A pyosalpinx may give the same sensation.

The obese abdominal wall

The obese patient may be convinced she has a tumour although she is only putting on weight (phantom tumour). Palpation is difficult; but the percussion note in the lower half of the abdomen will be resonant.

Rectus sheath haematoma

This rare condition presents as a fixed abdominal mass, accompanied by pain, and usually follows sudden exertion such as severe coughing.

Mesenteric cyst Hydatid cyst Pancreatic cyst Large hydronephrotic kidney

These are all rarities in the UK but must be considered if the physical signs are equivocal and especially if the swelling is not in the midline. Modern imaging techniques should differentiate.

Broad ligament cysts

The distinction is not likely to be made before laparotomy, even with imaging, if the intact ovary is observed on the back of the swelling.

Ectopic or transplanted kidney

These abnormalities are rare, but as they are usually detected for the first time on bimanual examination, they must be borne in mind. The ectopic kidney can lie anywhere in the pelvis and derives its blood supply from the iliac vessels. The ureter often runs a tortuous course.

Retroperitoneal tumours

Retroperitoneal, in the surgical sense, means behind the peritoneum of the posterior abdominal wall. Such tumours are rare but may arise from any connective tissue, a lipoma being the commonest. Examination reveals a fixed tumour. The tumour may displace the ureter and is in close relation to the large vessels.

Ovarian cyst accidents

Complications of ovarian tumours

Torsion of the Pedicle

(Axial rotation)

This is the commonest complication and may occur with any tumour except those with adhesions. The thin-walled veins of the pedicle are obstructed first while the arterial supply continues. As a result there is haemorrhage into the tumour and into the peritoneum, and if not treated, significant infection may occur.

Clinical features

Subacute

The patient complains of recurrent abdominal pain which passes off as the pedicle untwists. There is a rise in pulse and temperature during the bleeding, and over a period, anaemia develops.

Acute

The signs and symptoms are those of an acute abdominal condition. The problem becomes one of a differential diagnosis to exclude those conditions in which a laparotomy is not needed and those in which a laparoscopy may be useful.

Pain tends to be intense and continuous.

Differential diagnosis

‘Surgical conditions’ (i.e. those conditions commonly seen and dealt with by a general surgeon).

Acute appendicitis

Inflammatory bowel disease

Obstruction of bowel

Diverticulitis/diverticular abscess

Management

Patients presenting with an acute abdomen should first be stabilised. Once stabilised, investigations to establish wellbeing and potential causes may then be undertaken with blood tests and imaging. In cases where there is no resolution with conservative treatment, then, a diagnostic laparoscopy and/or a laparotomy may be needed. If the ovulation bleeding is greater than usual the woman may show quite, marked signs of peritonism. The corpus luteum may thereafter become exaggeratedly cystic and mislead the examiner.

Rupture of ovarian cyst

Rupture may be either traumatic or spontaneous and may occur in the following conditions:

1. Following torsion of a pedicle.

2. During bimanual examination.

3. During labour when the cyst is impacted within the pelvis.

4. Spontaneous rupture. This is not uncommon, especially with malignant cysts, where the epithelial tissue outgrows the connective tissue.

Benign and malignant ovarian tumours

Ovarian cysts can grow to a significant size before causing any symptoms. Ovarian cancer has been described as the ‘silent killer’ as approximately 60% of women present with advanced disease. While many patients, in retrospect, do have symptoms, they are non-specific and do not at first seem to be due to ovarian disease.

Clinical features

The patient usually has non-specific symptoms and appears well. Symptoms may include abdominal pain, bloating, changes in bowel habits, urinary symptoms and pelvic symptoms. Not unsurprisingly, many women are initially misdiagnosed with irritable bowel syndrome and/or are initially referred for general surgical review. However, referral from primary care was not found to be significantly delayed and did not have an impact on survival.

Investigation

Once a pelvic mass is suspected it should be investigated with tumour markers, as previously discussed. Imaging with ultrasound will delineate complex features (ascites, bilateral masses, thick septa, metastatic deposits, solid areas) and allow the calculation of a risk of malignancy index (RMI). This is calculated as below:

Score	Menopausal status	Ultrasound
1	Premenopausal	1 abnormality
3	Postmenopausal	2 or > abnormality

Using a cut-off value of 200, the RMI has an 80% positive predictive value for ovarian malignancy. CT scanning will provide further information on the extent of disease. Using both the RMI and CT findings, patients can then be referred directly to specialist gynaecological oncology surgeons.

Histological classification

Ovarian tumours can arise from the ovarian epithelium, stroma or the germ cells. The embryonic coelom, from which the epithelium develops, also gives rise to the Müllerian duct from which develop the structures of the genital tract; and it is this common origin which accounts for the great variety of epithelial patterns encountered.

Epithelial Tumours

Serous cystadenoma or cystadenocarcinoma.

Mucinous cystadenoma or cystadenocarcinoma.

Endometrioma or endometrioid carcinoma.

Clear cell carcinoma.

Brenner tumour.

Germ Cell Tumours

Carcinoid hormone-producing

Thyroid tumour choriocarcinoma

There is one well-known secondary tumour of the ovary, the Krükenberg tumour, which is secondary to a Gastric carcinoma. This term is now being widely used to describe metastases to the ovary from other cancers such as breast and colon cancers.

Risk factors for ovarian cancer

Carcinoma of the ovary

In developed countries, women have a lifetime risk of about 1.4% for developing ovarian cancer, which is slightly greater than the risk of cervical or endometrial cancers, but well below the 13% lifetime risk of breast cancer.

5–10% of ovarian cancers are related to genetic factors such as BRCA gene mutations or the Lynch syndrome of familial breast, colorectal and ovarian cancers. The induction of ovulation with Clomiphene for more than a year carries a 10-fold increased risk of ovarian cancer. Long-term oral contraceptive use reduces the incidence of ovarian cancers.

BRCA 1

The mutation is located on chromosome 17. Those affected carry a 30–60% risk of developing ovarian cancer. Survivors of breast cancer have a 13% risk of developing ovarian cancer within 10 years.

BRCA 2

The mutation is located on chromosome 13. Those affected carry a 20% risk of developing ovarian cancer. Survivors of breast cancer have a 7% risk of developing ovarian cancer within 10 years.

If family members are identified as having a mutation, then, they may be offered risk reducing surgery such as prophylactic bilateral salpingo-oophorectomy.

Ovarian cancer risk factors

Increased	Decreased
Low parity	High parity
Infertility	Combined contraceptive pill
Endometriosis	Breastfeeding

Ovarian metastases from extra-genital tumours are not uncommon. The commonest sites of primary growth are the breast, stomach and the large intestine. They usually occur in functioning ovaries and their importance lies in the fact that these metastases grow to a large size while the primary growth is small and give rise to no clinical manifestations. The metastases usually reproduce the histological characteristics of the primary cancer.

Epithelial ovarian tumours

Serous cystadenoma

It can be a unilocular or a multilocular cyst. They are the most common benign epithelial tumours and form 40% of all epithelial tumours. They are bilateral in 10% of cases. They show one of three structures:

(1) A simple cystic form with a smooth surface and a smooth lining.

(2) A cystic structure with intracystic papillary formations. The latter may be sessile buttons or pedunculated, frond-like projections.

(3) An adenomatous form where many of the loculi are small and the papillary structures are solid and complex.

Microscopically, the tumour has a fibrous capsule. Septa support the cysts which are lined by cuboidal epithelium and contain thin serous fluid.

Serous cystadenocarcinoma

This is by far the commonest primary carcinoma, and in over half the cases, it is bilateral. The cysts are always of the papillary type and the epithelium burrowing through the capsule produces papillary processes on the serous surface. Extension of the growth to the pelvis and adjacent organs fixes the tumour. It commonly spreads across the peritoneal surface tissues becoming densely adherent, but at times, it can invade tissues directly. Ascites are frequently present.

Mucinous cystadenoma

It is a unilocular or multilocular cyst of an ovary lined by a tall columnar epithelium, resembling that of the cervix or the large intestine. They can be large and may reach immense proportions, occupying the whole peritoneal cavity and compressing other organs. It may occur at any age.

The surface of the cyst is often completely smooth and round, but may be slightly nodular, due to the projecting loculi.

The cut surface of the cyst is multilocular and has a mosaic pattern.

Microscopically, the tumour has an outer fibrous capsule from which the septa extend to support the walls of the cysts. The latter are lined by tall columnar epithelium with basal nuclei and contain a gelatinous glycoprotein or mucin.

The signs and symptoms are similar to those generally associated with any non-functioning ovarian tumour. Rupture may occur and seeding of the epithelium on the peritoneal surface may cause a pseudomyxoma peritonei.

Pseudomyxoma Peritonei

This rare condition, occasionally, but not inevitably, follows the rupture of a mucinous cystadenoma (page 260). The epithelial cells get implanted on the peritoneum and continue to secrete mucin. The abdominal cavity is eventually filled with the jelly, while the secreting cells spread over the parietal and the visceral peritoneum. The disease develops slowly over several years and may require multiple operations to strip the mucin plaques. Current research is focusing on hot intraperitoneal chemotherapy. This disease is, commonly, chronically progressive.

Mucinous cystadenocarcinoma

This is only a third as common as the serous variety. Malignancy in a mucinous cyst is characterised by the formation of areas of solid carcinoma in the wall. The cells are columnar, show mitoses and tend to form glandular structures.

Germ cell ovarian tumours

Germ cell tumours may be:

Undifferentiated	Dysgerminoma Gonadoblastoma
Differentiated	Embryonal Teratomas Extra-embryonal Yolk sac tumour Choriocarcinoma

Clinical features

97% of these tumours are benign but they comprise 20% of all ovarian tumours. Patients are usually young, in the 20–30 year-old age group. They may present with an acute abdomen as the pelvic masses undergo torsion or rupture. In some, the pain can be of a more chronic nature. However, many women are often diagnosed incidentally, while undergoing investigations for other reasons.

Treatment

This will depend upon the age of the patient, the extent of the disease and fertility wishes. Where fertility is not an issue, then usually, bilateral salpingo-oöphorectomy and hysterectomy are indicated. Where fertility preservation is an important issue, evidence supports the strategy of unilateral salpingo-oöphorectomy with thorough assessment. All disease should be cyto-reduced at a laparotomy to the smallest possible level.

Disease is staged as for an ovarian carcinoma. If the disease is greater than Stage 1A, then postoperative chemotherapy is indicated to reduce the risk of recurrence and provide patients with a good long-term outcome or even a cure.

Germ cell ovarian tumours – undifferentiated

Dysgerminoma

This is the only solid ovarian tumour of characteristic appearance. Usually ovoid with a smooth capsule, it is of rubbery consistency and greyish colour. It is most common in the younger age groups and is bilateral in 20%. About 70% of the cases are Stage 1A at diagnosis. Lactate dehydrogenase (LDH) levels may be elevated. Survival rates are greater than 90% for stage 1 tumours.

Microscopically, it consists of masses of large, clear, epithelial cells with large nuclei, resembling primitive germ cells, in cords or alveoli. Fine connective tissue that has been infiltrated by lymphocytes separates the bundles of epithelial cells. The malignancy varies, but many appear to be relatively benign and do not recur. Those in children tend to be more malignant.

Gonadoblastoma

This is a tumour associated with dysgenetic gonads, usually streak gonads. The patient is an apparent female and may have a diminutive uterus, tubes and vagina, but usually there is a sex chromosome mosaicism such as 45X/46XY.

The tumour is composed of two types of cells: (a) a large primitive germ cell and (b) small cells of the granulosa type. Call-Exner bodies (small rosettes) may be seen in the latter. These two types of cells form epithelial islands in a stroma which may contain Leydig-like cells. Sometimes, the germ cells may undergo rapid proliferation and give rise to a dysgerminoma. Some of the dysgerminomata in children probably arise in this way. Choriocarcinoma may also originate in a gonadoblastoma.

About 60% of women show some signs of virilisation and 17-ketosteroid excretion may be raised.

Teratomata

These are broadly divided into mature and immature forms.

Other ovarian tumours

Krukenberg Tumour

This is a secondary carcinoma of the ovary. It is remarkable for its characteristic histological appearance and the fact that the primary growth, which is usually seen in the stomach and less commonly in the large intestine, is often clinically silent. The ovarian tumours are frequently bilateral, of equal size, smooth and lobulated. They remain freely mobile with no adhesions. Being firm and fibrous in appearance they are frequently mistaken for fibromata, but these are usually unilateral.

Histologically, they have a well-defined appearance. There is a very cellular stroma, resembling a sarcoma, in which there are large epithelial cells lying singly or in alveoli. These epithelial cells have a clear cytoplasm with a crescentic nucleus that has been pushed to one side, giving a signet-ring appearance that is typical. The cytoplasm is full of mucin.

The majority of patients with this tumour have a poor prognosis.

Hormone-producing tumours

Brenner Tumour

A benign tumour, mainly solid and most common in the 6th decade, it is composed of fibrous and epithelial elements in varying proportions. It forms 2% of all solid ovarian neoplasms.

It is usually solid and resembles a fibroma. Occasionally, there may be microcysts or even an associated large mucinous cyst. Microscopically, it is mainly composed of fibrous tissue with small islands of clear epithelial cells of squamous appearance. Sometimes the islands become cystic and the epithelial cells become mucinous.

The most common tumours of this kind are steroid-producing, particularly sex steroids. Both androgenic and oestrogenic effects have been described with every histological variety as some tumours have a mixed steroid cell composition, but certain tumours of well-defined histological structures are commonly associated with the production of only one type of steroid.

Oestrogen-producing tumours

These belong to the granulosa-theca cell group and are found in all ages. They account for 3% of all solid tumours of the ovary.

Oestrogen excess can cause hyperplasia of:

1. Myometrium → enlarged uterus.

2. Endometrium → Irregular and/or postmenopausal bleeding.

3. Breast tissue → enlargement, tenderness of breasts.

In childhood there is accelerated skeletal growth and appearance of sex hair.

5% of these occur in children → precocious puberty.

60% occur in child-bearing years → irregular menstruation.

30% occur in postmenopausal women → postmenopausal bleeding.

Diagnosis

Granulosa cell tumour in childhood may be found as the cause of female precocity with a pelvic mass being demonstrated on imaging. Following puberty, and even into postmenopausal years, diagnosis on clinical grounds is difficult owing to the multiplicity of factors that can cause irregular vaginal bleeding. Often, the diagnosis is made following the removal of an abnormal cyst or ovary.

Pathology

These tumours vary very much in function. Large tumours may be virtually functionless. In childhood and early adult life, the tumours are composed mainly of granulosa cells. In later life they are usually thecomata. The granulosa-cell type of growth should be considered as a carcinoma. Recurrence may occur many years after removal of the primary growth. It is not possible to accurately correlate malignancy with histological appearances. In 14% of the cases endometrial hyperplasia becomes atypical and an endometrial carcinoma develops.

Fibroma

This is composed of fibrous tissue and resembles the fibromata found elsewhere. It is most common in the elderly and accounts for 4–5% of all ovarian neoplasms.

The fibroma is believed by many to be a thecoma which has undergone fibrous transformation. It is sometimes associated with Meig’s syndrome where a pleural effusion is also noted.

Androgen-producing tumours

Three distinct types of masculinising ovarian tumour are recognised: (a) Sertoli-Leydig cell tumour (arrhenoblastoma), (b) Hilar cell tumour, (c) Lipoid cell tumour. All the three can cause amenorrhoea.

Sertoli-leydig Cell Tumour

This is a rare tumour and accounts for much less than 1% of all ovarian tumours. It occurs in young adult females. Clinically two stages are recognised:

Pathology

It usually appears as a small white or yellowish tumour within the ovarian substance. Cystic degeneration may occur. These tumours are usually only of a low-grade malignancy.

Histologically it consists of primitive tubules surrounded by Leydig cells which contain crystalloids of Reinke. These are rod-shaped structures in the cytoplasm of Leydig cells and are said to be diagnostic of these cells.

Biochemistry

The symptoms are due to the secretion of testosterone. The quantities of 17-ketosteroids are within the normal range, unlike in adrenal virilising tumours where their levels may be elevated. Direct estimations of blood testosterone can be made. Some of these tumours secrete oestrogens. Removal of the tumour results in regression of symptoms in the same order as their appearance. Menstruation returns within a month or two. Voice changes tend to be permanent.

Hilar Cell Tumour

This is a very rare tumour found in postmenopausal women. Defeminisation occurs but signs of virilism are usually mild, consisting of hirsutes, alopecia and an enlargement of the clitoris.

Pathology

Hilar cell tumours are small, brown, simple tumours of the ovarian hilum consisting of polyhedral Leydig cells. Crystalloids of Reinke are occasionally present. 17-ketosteroids are usually within the normal postmenopausal range. Small quantities of androgen are produced.

Lipoid Cell Tumour (Ovoblastoma, Masculinovoblastoma, Adrenal-like Tumour)

This is also a rare tumour that causes masculinisation and produces symptoms and signs of Cushing’s syndrome such as skin striae, obesity, polycythaemia, impaired glucose tolerance and hypertension.

Pathology

The tumour consists of cells with high lipid content and are commonly large and yellowish.

Unlike other virilising tumours, the 17-ketosteroid output is greatly increased and the excretion of 17-hydroxycorticosteroids is also raised. ACTH or chorionic gonadotrophin will cause a further increase, but dexamethasone does not diminish the output, thus helping to differentiate the condition from virilising adrenal tumours.

Other Hormone-Producing Tumours

Carcinoid (Serotonin-Producing Tumour)

This tumour arises in association with a cystic teratoma of the ovary from cells related to the respiratory or intestinal epithelium that are sometimes found in these cysts.

It may give rise to a typical carcinoid syndrome with patchy cyanosis, flushing, diarrhoea, intestinal colic, oedema and cardiac failure due to a tricuspid valve lesion. Usually the syndrome does not appear until the tumour has metastasised to the liver.

Struma ovarii (Thyroid Type Tumour)

Small foci of thyroid tissue are common in ovarian teratomata, but large amounts are rare and functioning thyroid tissue is even rarer. When the thyroid tissue actually proliferates and forms a tumour, 5–10% of these become malignant.

Choriocarcinoma of the ovary

This is an extremely rare tumour of the ovary. It is also known as a non-gestational choriocarcinoma, in that it does not arise as a consequence of conception. Most commonly, it is associated with a dysgerminoma and both, in turn, may be derived from germinal cells in a dysgenetic gonad. A syncytiotrophoblast is always present, but sometimes a cytotrophoblast is also formed. The principal hormone produced is β-human chorionic gonadotrophin (βHCG). This can prove to be useful in the diagnosis and follow-up of these tumours. Metastases may occur, as in any choriocarcinoma.

Hormone production by non-functioning tumours

Occasionally, the presence of tumour growth in the ovary induces a thecal transformation of the ovarian stroma which in turn produces steroids, sometimes androgenic, but more commonly oestrogenic. This has been reported in association with benign and malignant cysts, Brenner tumours, fibroma and secondary carcinoma of ovary. The secretion of steroids can result in menstrual disorders, and in the case of androgens, virilisation.

Surgical treatment of ovarian tumours

Benign ovarian tumours that are greater than 10 cm in diameter must be removed, but clinically and ultrasonically diagnosed cysts below 10 cm in women under 35 years of age may be reviewed in a few months if there is no suspicion of a malignancy. A follicular or luteal cyst may resolve spontaneously.

Cystectomy: It involves enucleation of the tumour from its capsule of ovarian tissue, which is then rolled into a little bundle and held together with sutures, thus preserving ovarian function.

Indications:

A tumour that is apparently benign.

This operation would not be feasible in the case of a very large tumour, or where there had been previous inflammation.

Ovariotomy: Removal of an ovary containing a tumour. (Removal of an ovary not containing a tumour is called oöphorectomy.)

Indications:

(a) Malignancy. (The uterus and other ovary are also removed.)

(b) The patient declines a hysterectomy and the other ovary is normal.

Laparoscopy: This may be diagnostic and/or therapeutic – small benign cysts may be removed. Where a malignancy is not suspected on the basis of preoperative investigations, some larger simple cystic lesions can be placed in a laparoscopic bag for removal and then aspirated to reduce their size before removal.

Treatment of ovarian cancer

Epithelial ovarian cancer is now the most frequent cause of death from gynaecological malignancy. The principles of treatment are:

1. Surgical staging.

Ovarian carcinoma is staged surgically, so laparotomy is an essential part of its management in most patients.

2. Surgical debulking of tumour volume.

Surgical removal of as much malignant tissue as possible, even if this should call for resection of structures outside the normal field of the gynaecologist.

3. Adjuvant chemotherapy.

This is followed-up with intensive chemotherapy. Currently, the most commonly used regimen is taxanes (paclitaxel) combined with the platinum compound, carboplatin.

Surgery remains an important aspect of management and referral to a specialised gynaecological oncology surgeon at the initial laparotomy has been shown to provide the best outcomes. Co-operation with a colorectal surgeon may be necessary. Increasingly, some centres offer chemotherapy prior to surgery, with an operation after three of the six planned chemotherapy treatments so as to reduce the incidence of surgical morbidity.

The diagnosis of ovarian cancer is often delayed due to the non-specific nature of the symptoms. Accordingly, as many as 66% of patients will be at an advanced stage, at the time of presentation.

Spread of ovarian cancer

It is important to know the direction of spread of ovarian cancers, so that the true extent of the disease and the symptoms that it may induce can be recognised and managed.

1. Direct

Spread directly into neighbouring structures – uterus, bladder or bowel.

2. Transcoelomic

Cancer cells are carried across the peritoneum and achieve widespread seeding. This results in tumour deposits in the peritoneum, bowel mesentery, visceral surfaces and the omentum. The tumour marker CA125 is usually raised in advanced ovarian cancer and is used to assess the response to chemotherapy.

3. Lymphatics

Ovarian drainage is to the para-aortic glands, but sometimes also to the pelvic and even the inguinal groups. Cells seeded on to the peritoneum are drained via the lymphatic channels on the underside of the diaphragm into the subpleural glands and thence to the pleura.

4. Blood stream

Blood spread is usually late and is to the liver and the lungs.

All patients with an elevated risk of malignancy should be discussed at a preoperative multi-disciplinary meeting. The management of all patients remains as a combined surgical and chemotherapeutic regimen – primary surgery followed by adjuvant chemotherapy. Surgery may be delayed until three cycles of chemotherapy have been administered in selected cases – ‘delayed primary surgery’.

The objectives are:

1. To classify the growth according to its extent of spread (staging) as accurately as possible.

2. To remove as much cancerous tissue as possible (‘surgical debulking’; ‘cyto-reductive treatment’).

Chemotherapy is recommended for all stages of ovarian tumour greater than Stage 1B grade 2.

Incision

A vertical incision, which can be extended, is essential to allow a full inspection. Reduction of a cyst by tapping and extraction through a suprapubic incision is not an acceptable practice. Surgical rupture of a cyst will increase its staging to a 1C tumour from what may have been a Stage 1A tumour. This has important implications for patient management.

Inspection

The entire peritoneal cavity must be palpated, including the liver, subdiaphragm, bowel and mesenteries, omentum and nodal areas. Suspicious areas are to be biopsied or removed.

Organs removed

These must always include the uterus, tubes, ovaries, appendix and the omentum. Partial resection of bladder and bowel may also be required, but an epithelial cancer tends to spread over invaded tissue rather than penetrate it, and a plane of cleavage can often be found. The best patient outcomes are associated with either a complete or an optimal cytoreduction. The definition of optimal can vary but at least to a size of <2 cm largest tumour deposit or, preferably <1 cm largest tumour deposit.

Cytology

Before handling the tumour, specimens of ascitic fluid or peritoneal saline washings for cytological examination must be taken.

Principles of chemotherapy

Malignant tumour growth

Tumour growth is a result of the failure of normal cell cycle control and a failure of apoptosis (the natural mechanism for removal of abnormal cells). Tumour cells multiply at the same rate or more slowly than normal cells, but have more actively dividing cells that are not subjected to the same physiological control, so that a cancer gradually develops.

Mode of chemotherapeutic action

Chemotherapeutic agents in ovarian cancer

The current first line agents used in ovarian cancer treatment are carboplatin and paclitaxel. Carboplatin is an alkylating type agent that forms DNA cross links that prevent cell replication, ultimately leading to cell death. Paclitaxel similarly prevents cell replication by acting on another aspect of the cell, namely interfering with cell microtubule formation.

The antimetabolites inhibit DNA synthesis by disrupting essential metabolic events in nucleic acid synthesis. Another currently used treatment is liposomal doxorubicin which is an anti-mitotic agent with a complex mechanism of action that includes prevention of RNA synthesis, where the agent is delivered in liposomes to enhance its mechanism of action.

Hormonal therapies are employed to either directly bind to nuclear steroid receptors or influence the production of steroids that can bind to the nuclear steroid receptors. By binding to such receptors they can influence steroid gene regulation to bring about an antitumour effect. Response rates have been noted in ovarian cancer treatment and they are well-tolerated therapies.

Targeted anticancer therapies are currently being investigated as new therapies to increase the efficacy and decrease the toxicity of traditional chemotherapy. They target different pathways that are important for cancer growth and metastasis such as angiogenesis, cell cycle and the apoptotic pathways.

Chemotherapy trials are leading to evolutions of standard therapies. It has been noted that patients involved in chemotherapy trials have better outcomes than those not involved in these trials.

Chemotherapy toxicity

Common adverse effects of chemotherapy include nausea, vomiting and fatigue. Such side effects can be controlled well with antiemetics. Other side effects are related to the individual drugs. Carboplatin is well tolerated in general but is often myelosuppressive, necessitating blood transfusions or delayed treatments. Paclitaxel will lead to alopecia and it can also cause neuropathy, arthropathy and myalgia. Liposomal doxorubicin has a particular side effect called palmar/plantar erythema and it can also be cardiotoxic.

Present prognosis for invasive epithelial ovarian cancer

Stage	5-year survival (%)
I	76
II	37
III	27
IV	15

Borderline epithelial tumours have excellent 5-year survival rates of 90–95% and a 15-year survival rate of 70–85%.

Broad ligament cysts

Broad ligament cysts (Parovarian Cysts)

The epoophoron lies in the mesosalpinx and is parallel to the uterus. At about the level of the internal os it penetrates the muscle of the uterus and descends into the cervix and vaginal wall, to the hymen.

Parovarian cysts derived from the epoophoron are unilocular and contain watery fluid without mucin. The wall is thin and lined with a layer of cuboidal cells that can sometimes be ciliated.

If one imagines any of these locations (marked X) expanding like a balloon, the resulting displacement of tissues is easily understood.

Diagnosis

On palpation, the cyst, which is not mobile, may displace the uterus and may be closely related to it. An ovarian cyst with adhesions may feel very similar and it is seldom possible to distinguish between the two before a laparotomy.

Operation

Great care must be taken while identifying tissues, as the location of the original site of the cyst determines its displacement and its characteristics.

In the outer third of the broad ligament, the cyst tends to develop a pedicle.

In the middle of the broad ligament, the tumour is sessile but relatively fixed.

The ovarian vessels are displaced and may be stretched leading to interference with the ovarian blood supply.

It is possible for the ureter and uterine artery to be displaced outwards, but usually they are below and medial to the cyst.

The tumour may increase in size and strip the peritoneum off the pelvic walls and spread laterally and posteriorly, obliterating the Pouch of Douglas.

The broad ligament is incised anteriorly where the blood vessels are few, and the cyst is enucleated digitally. The oozing area is now exposed and should be obliterated. Care is necessary to avoid damage to the blood vessels, ureter and bladder. Redundant broad ligament may have to be excised.

Cysts of kobelt’s tubules, hydatids of morgagni, fimbrial cysts

These are names given to small cysts found in the mesosalpinx and around the terminal portion of the fallopian tubes. They are of indeterminate embryonic origin and are of no clinical significance.

Carcinoma of fallopian tubes

The fallopian tubes are often involved in an ovarian carcinoma but an isolated fallopian tube carcinoma is very rare. There is, however, some evidence to suggest that ovarian carcinomas in BRCA gene mutation patients may actually arise from the distal fallopian tube.

Pathology

The growth is usually an adenocarcinoma of the tubal epithelium which grows inwards and secretes a copious amount of serosanguinous fluid which discharges per vaginam, if the proximal tube remains patent. This classical sign of a tubal carcinoma is rare.

Clinical features

The patient is usually in her fifties and often nulliparous or of low parity. She may complain of postmenopausal bleeding, pain, and sometimes, a watery vaginal discharge. In the absence of definite symptoms the diagnosis is often made rather late. Pelvic signs suggestive of infection in a postmenopausal woman should always be investigated. The differential diagnosis includes carcinoma of the uterus or the ovary.

Aetiology is unknown, but increasing evidence suggests that some are BRCA linked.

Clinical staging

Stage I	confined to one or both tubes
Stage II	pelvic extension
Stage III	spread to other structures (omentum, bowel, etc.), positive retroperitoneal or inguinal nodes or superficial liver metastases
Stage IV	distant metastases (including bladder), pleural effusion with positive cytology or parenchymal liver metastases