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PENYAKIT GINEKOLOGI DEWI PUSPITA

Ovarian cancer
Cancer of the uterine corpus
Cancer of the cervix
Vaginal and vulval cancer
Trophoblastic tumours
OVARIAN CANCER
Fifth commonest cancer in women, with over 6000 cases diagnosed and over 4000
women dying of the disease each year in the UK. Incidence slowly rising.
The majority of cases occur over the age of 55y, with the peak in the 65–75y age
group.
ETIOLOGY

• The risk of ovarian cancer relates to the number of ovulatory cycles in a woman’s
lifetime and multiple pregnancies.
• Use of the oral contraceptive pill now shown to offer protection;infertility or its
treatment may increase the risk.
• A bout 5% are clearly hereditary—associated with BRCA1 or BRCA2 or Lynch
families.
PATHOLOGY
80% of ovarian malignancies are epithelial. Serous and endometrioid cancers are
the commonest forms, but about 5% are mucinous or clear cell. Clear cell cancers
account for up to 20% in the Far East.
• The rest comprises germ cell, sex cord/stromal tumours, sarcomas, and
neuroendocrine cancers.
CA125 (MARKER)
Eighty per cent of women with advanced ovarian cancer have elevated serum
CA125, and this marker is valuable in monitoring the response to therapy and in the
detection of early relapse. However, it is not specific for ovarian cancer and is
elevated in association with other peritoneal pathologies.
A ratio of CA125 and CEA that is higher than 25 may help to support the diagnosis
of epithelial ovarian cancer (EOC).
PRESENTATION AND STAGING

The majority of women present with disease that has spread beyond the ovary to involve the
peritoneum and other abdomino-pelvic organs.
The commonest symptoms are abdominal discomfort and swelling, bloating, and change in
bowel habit. GI and urinary symptoms also occur.
20.1) and the amount of residual disease after surgery. The 5y survival rates,
According to the stage, are as follows:
• stage I, 80%; but over 90% for stage IA
• stage II, 45%
• stage III, 20%
• stage IV, <10%.
STAGING OF OVARIAN CANCER
TREATMENT OF EPITHELIAL OVARIAN
CANCER
• This should also include thorough staging, with removal of the omentum, peritoneal
washings, inspection of the subdiaphragmatic areas, and, more controversially,
lymphadenectomy.
• The amount of residual disease correlates with worse prognosis.
• The majority of patients present with advanced disease (stages II–IV), with a
correspondingly poor prognosis.
• P atients who have >2cm of disease after their initial surgery have a poor prognosis,
with only 20% of patients surviving 3y.
• The median survival times for patients with suboptimally debulked disease (>1cm)
range from 16 to 29mo, and from 26 to 96mo for patients with optimally debulked
disease.
FIRST-LINE CHEMOTHERAPY
Chemotherapy is usually offered to all patients, except possibly stage Ia G1. Platinum and a taxane are
usually standard, but there is a body of opinion which recommends carboplatin alone, based on the ICON 3
(International Collaborative Ovarian Neoplasm) trial, reserving taxanes for relapse.
• P latinum-based therapy is usual—carboplatin is equivalent to cisplatin, but with less toxicity.
• Taxanes are usually given in combination in most centres.
• In older or unfit patients, single-agent carboplatin is used.
• To date, the addition of a third drug or alternating doublets has failed to improve survival.
• Maintenance treatments have also failed to show survival benefit as yet.
• Intraperitoneal chemotherapy in optimally debulked patients has been shown to improve survival in four
randomized trials but has been slow to be adopted universally because of toxicity and inconvenience.
• Currently, there are many trials investigating the addition of targeted anti-cancer treatments, but their exact
role remains to be defined, until these trials are complete; at the time of writing, the VEGF receptor
CANCER OF THE CERVIX
Unprotected sexual intercourse.
• HPV.
• HP V types 16 and 18—the US and Europe.
• Vaccination programme started in Europe in 2008.
• H ighly variable incidence rates in different countries.
• Globally, second commonest cancer in ♀.
EPIDEMIOLOGY
The epidemiology of this disease has been extensively studied, and strong associations
demonstrated with:
• social deprivation
• multiparity
• cigarette smoking
• early onset of sexual intercourse (before 17y)
• non-barrier forms of contraception
• reduced incidence and mortality in those countries with population screening.
More recent studies have focused attention specifically on papillomavirus transmission and
the increased susceptibility of the cervical epithelium of the sexually active teenage ♀.
PATHOLOGY
When the disease is confined to the cervix, patient management depends on the
cytology and/or histology specimens. These can reveal a spectrum of changes in the
epithelium of the cervix:
• slight dysplastic changes to the cell architecture
• viral cytoplasmic changes
• CIN 1, 2, or 3
• micro-invasive carcinoma
• frank invasive carcinoma
These early changes may first be identified by examination of a smear of cells, collected by
a special wooden (Ayers) spatula or a brush, from the vaginal surface of the cervix. The
specimen is a sample of the cells that are being shed from the ectocervix, sometimes along
with cells that are being shed from the endocervix and endometrium. They are examined on
a slide after staining with Papanicolaou stain, and an impression of the health of the
epithelium can be formed.
To accurately map the changes in the cervical epithelium, patients require colposcopy where
the cervix is examined by binocular microscopy at ten times the normal magnification.
Viral changes, dysplasia, and CIN 1 and 2 are common in the sexually active adult ♀,
particularly among those in their 20s when multiple partners and non-barrier
contraception are involved. They can all revert to normal without treatment and are
monitored by regular smears. CIN 3 changes are more commonly part of a process
that can progress over months or years to invasive carcinoma.
STAGING & PRESENTATION

The FIGO staging system (see Table 20.3) is based predominantly on the extent of
the tumour. Metastatic spread is normally by the lymphatic system.
• CIN and micro-invasive carcinoma usually have no symptoms.
• The earliest symptoms of invasive carcinoma are:
• vaginal discharge
• post-coital bleeding
• intermenstrual or post-menopausal bleeding
• backache from hydronephrosis and nodal spread.
INVESTIGATIONS

Asymptomatic patients with CIN 1, 2, or 3 or micro-invasive carcinoma do not require


any further investigation prior to treatment. Symptomatic patients should have an
examination under anaesthetic to complete FIGO staging, cystoscopy, or
sigmoidoscopy if these adjacent organs appear to be involved.
CT or MRI scanning of the pelvis and abdomen define more fully the size of the
tumour and any lymphadenopathy.
PET-CT is increasingly used, as it is more likely to show occult metastases and change
the treatment plan.
IVU is now considered obsolete.
MANAGEMENT (SURGERY)
CIN 3 disease localized to the ectocervix—colposcopy and loop diathermy,
cryoprobe, or laser:
• laser produces less distortion and more rapid healing. Diathermy is inexpensive and
easy to learn.
• CIN 3 disease extending into the endocervical canal or micro-invasion—cone
biopsy.
• Complete excision still requires follow-up or, if the patient wants no more children,
hysterectomy and surveillance for the vaginal vault.
• Invasive carcinoma (<4cm, confined to the cervix)—Wertheim’s hysterectomy
removes the parametrium and pelvic nodes. A recent study with 30mo of survival
data has shown stage Ibi cervical cancer me with laparoscopic radical hysterectomy
and pelvic lymphadenectomy.
FIGO STAGING
RADIOTHERAPY
• Radiotherapy if:
• incomplete excision of the tumour
• poor tumour differentiation
• vascular invasion
• node involvement
• all other stages/medically unfit.
• E xternal beam irradiation, followed by intracavitary brachytherapy (ICT).
• 45–52Gy—pelvis over 5wk.
• Sterilizes pre-menopausal patients.• ICT γ sources (137Cs or 192Ir) in the uterus/upper
vagina.
Inserted for minutes (HDR); multiple fractions:
• inserted for 724h for MDR.
• ICT—dose to central pelvic structures:
• target dose of 75–85Gy to tumour volume ‘A’ point
• dose to the bladder and rectum below 70Gy
• moving towards customized planning with CT/MRI.
• P elvic radiotherapy for advanced cancer:
• minor side effects are common, e.g. 10–20%
• up to 5% serious late morbidity (bowel and urinary tract)
• bleeding from proctitis or cystitis
• stricture or ulceration
• fistula
• vaginal shortening/dryness.
CHEMOTHERAPY
Patients with recurrent pelvic, or systemic metastatic, disease may benefit from palliative
chemotherapy. The principal active agents are:
• cisplatin
• MMC
• ifosfamide
• MTX
• fluorouracil
• bleomycin
• paclitaxel
• topotecan.
CONCOMITANT CHEMO-IRRADIATION

The NCI consensus statement of 1999 of clinical trials of chemo-irradiation for


cervical carcinoma concluded that there was significant improvement in the OS, local
control, and risk of metastatic disease, compared with radiotherapyalone, with the
greatest evidence of benefit in stages IB–II disease.
All trials demonstrate increased toxicity with combined-modality treatment, so that
patient selection is important. A recent update has confirmed this benefit and again
shown maximal benefit in earlier-stage disease.
RESULTS
Survival at 5y is typically as follows: stage Ia, 100%; stage Ib, 70–90%; stage II,
50–70%; stage III, 25–60%; stage IV, 10–20%. The wide ranges reflect the large
variation in disease volume seen within the present staging system, which is based on
tissue involvement, rather than the volume of disease.
Relapse after 5y is unusual.