Tuesday, October 30, 2018

ovarian cancer




Ovarian Cancer






Ovarian cancer is a form of cancer affecting an ovary. It usually develops from the surface coating of the ovaries. The most common form is epithelial carcinoma of the ovary. Rare forms, such as germ-like ovarian tumors or borderline tumors, warrant specific management.

Ovarian cancer is usually a bad prognosis because often found late. The ovary is located in the small pelvis and a tumor lesion can develop slowly without clinical signs. The treatment is based on the most complete surgery possible associated with chemotherapy that reduces the risk of recurrence. When cancer is very evolved, chemotherapy improves the quality of life of the patients and increases the survival time.

Epidemiology
The incidence is higher in Europe and the United States, compared to Japan and the less countries1 countries.

In 2005, and in France, the incidence of ovarian cancer was 8.1/100000 women, with a mortality rate of 4.6/100000 women. Peaks in incidence and mortality by age range from 55 to 94 years. With an incidence of 4.375 new cases diagnosed in France in 2005 it represents 3.2% of all new female cancers. With 3.180 deaths per year, ovarian cancer is ranked 13th in all cancer deaths, and ranked 5th among cancer deaths in Femme2, 3.

Estrogen-progestin contraception would significantly reduce the risk of this cancer4, which could explain the overall decrease in Incidence1.

Causes or risk factors
There is no specific cause of clearly recognized ovarian cancer, with the exception of "genetic" cancers (five to ten percent of the cases are familial associating breast and ovarian cancer either in the context of a type II Lynch syndrome or a mutation of U BRCA1 gene (17q21 chromosome) or BRCA2, an anomaly of the latter two genes being found in just over 10% of the cases of ovaire5 cancer).

Several external causes are nevertheless suspected or proven:
The use of alternative therapy for menopause would slightly increase the risk of ovarien6 cancer;
Exposure to food or drinking water that is too rich in nitrates (with cancer appearing in the elderly woman) 7 (as well as for vessie7 cancer);
Some medicines used in the treatment of sterility were suspected a time as possibly cancérigènes8. This was not confirmed in a study of large ampleur9;
Nulliparity (never having a child), early menstruation age, and late menopause would also be associated with an increase in risk1. Several explanatory assumptions have been given to this phenomenon: repeated trauma of the ovary by the number of OVULATIONS10, role of the secretion of gonadotropes11 hormones, of chronique1 inflammation;
The endométriose12.
Symptoms
They are non-specific, which partly explains the delay in diagnosis, but often present (in about 3/4 patients). The most frequent, according to a study of the JAMA13 are in order:

Back pain (45%)
Fatigability (or Asthenia) (34%)
Meteorism (swelling sensation of the abdomen) (27%)
Abdominal pain (22%)
Urinary symptoms (16%)
These symptoms can readily coexist, since most patients present at least two simultaneously.

Diagnosis
In front of the signs described above, the gynecologist or the GP asks for an abdominal and pelvic ultrasound that most often finds:

A mass in the small basin;
Fluid effusion in the abdomen (ascites);
Retro-peritoneal adénomégalies;
Diffuse lesions on the peritoneum, or even in the liver.
This ultrasound can also be done by trans-vaginal way, allowing to better visualize the PELVIENNES14 structures. The place of the scanner or magnetic resonance imaging remains to be evaluated.

Depending on the results of this ultrasound, it is suggested either a simple surveillance if the mass is not suspicious (it may be a benign ovarian cyst) or a biopsy under laparoscopy or laparotomy. In case the images observed at the ultrasound are highly suspicious, the laparotomy is often decided.

The diagnosis of ovarian cancer is done on a collection of abdominal abnormalities.

Tumor Markers
The dosage of CA 125 serum prior to surgery and before the onset of chemotherapy is a standard. However, this marker is not specific enough to be used, alone, for screening. It is useful in the patient's follow-up.

In young women, the dosage of AFP and HCG is recommended to exclude a germ tumor.
Pathology
Anatomopathologic Classification
Histopathological Classification of Ovarian epithelial carcinomas (WHO)
Cystadenocarcinoma Signet serous (42%)
Endometrioid carcinoma (15%)
Cystadenocarcinoma Signet mucinous (12%), poor prognosis
Clear cell carcinoma (6%), poor prognosis
Undifferentiated carcinoma
Mixed epithelial tumor
Non-epithelial lesions
Brenner tumor
Germ tumor
Sexual cord tumor (HCG)
Krukenberg tumor
Unclassified tumor
Krukenberg lesions are ovarian metastases of an adenocarcinoma of another origin (stomach, breast). Serous carcinoma of peritoneum is treated as an epithelial carcinoma of the ovary

Histopathological Grade
The rank has a prognosis and therapeutic interest, mainly for stage tumors FIGO I or II

Grade I: Differentiated
Grade II: Moderately differentiated
Grade III: Undifferentiated
Extension balance
In its natural evolution ovarian cancer gradually extends from the ovary to the pelvis, invades the peritoneum and finally disseminates metastases to the lung, liver and sometimes to the brain.

When the cancer is confirmed, the extension balance in addition to the exploration of the abdomen includes hepatic and thoracic imaging. The exploration of the abdomen is usually carried out during a laparotomy. It is this intervention that makes it possible to define precisely the stage of the disease. It is also at this point that the surgeon decides what type of intervention to do. The experience of the surgical team is paramount in the quality of the care.

The pleural effusions discovered on thoracic imaging must be punctured in search of cancer cells. Brain imaging (MRI or CT) is performed only if there are neurological signs for an attack.

The presence of lesions in the liver, pleura and lung are synonymous with a metastatic release.

Classification
It has been defined in 2002 by the International Federation of Gynecology and OBSTÉRIQUE15 and makes it easier to determine the prognosis.

Stage I: Tumor limited to ovaries
IA: Reaching a single ovary, capsule intact; No external vegetation, no ascites.
IB: Attainment of both ovaries, intact capsules; No external vegetation, no ascites.
IC: IA or IB tumor with capsular rupture or external vegetation or ascites or peritoneal washing liquid containing neoplastic cells.
Stage II: Ovarian tumor extended to other organs of the small basin
IIA: Extension to the uterus and, or to the fallopian tubes.
IIB: Extension to other organs of the small basin.
IIC: Tumor IIA or IIB with external vegetation or ascites or peritoneal washing liquid containing neoplastic cells.
Stage III: Ovarian tumor extended to extra-pelvic peritoneum and/or reaching the retro-peritoneal or inguinal ganglia (regional metastasis)
IIIA: Microscopic Extension to abdominal peritoneum.
IIIB: Macroscopic peritoneal localization (s) of less than 2 cm in diameter; Negative lymph nodes.
IIIC: peritoneal localization (s) greater than 2 cm in diameter, or with a peritoneal or inguinal retro ganglion.
Stage IV: remote metastasis. A cytological examination, in case of pleural effusion, is obligatory.
Prognosis
At diagnosis, the factors of good prognosis are (ESMO):

TNM Stadium
Small tumor (before and after surgery)
Young age
Good general condition
Tumor other than mucinous or clear cells
Well-differentiated tumor
Absence of Ascites
In the process of being supported:
The lack of standardization of CA 125 after 3 cycles is a bad prognosis factor
A recurrence less than six months after a platinum-based chemotherapy is a bad prognosis; Median survival of less than one year against more than three years if late recurrence.
The prognosis of ovarian cancer remains poor despite recent therapeutic advances. The late diagnosis of these lesions, at an advanced stage, is the main cause of this bad prognosis. At all stages, survival at five years is less than 40%. [Ref. Required]

Five-year survival is:

IA Grade 1: > 90%
IA ex Grade 1:80%
IB: 75%
IC: 70%
IIA: 60%
IIB/C: 55%
III without tumor residue: 40%
III with tumor residue: 20%
IV: < 10%
Treatment
Surgical
Surgery is a critical time in the management of ovarian epithelial tumors. In non-metastatic patients, the goal is a maximal cytoreduction. In metastatic situations, there seems to be an advantage to a maximale16 cytoreduction.

Surgery is described as:

Complete when the post-operative tumor residue is nil;
Optimum when the tumor residue is less than 1 cm;
Sub-optimal when the residue is greater than 1 cm;
Palliative when no gesture of resection can be achieved.
Initial laparotomy
Essential time of treatment, Laparotomy has a first time of exploration of the peritoneal cavity, of sampling, and then of resection. FIGO has published recommendations for the surgery of ovarian epithelial tumours.

It has a median incision. Peritoneal cytology is done either by taking the ascites fluid or by irrigating the peritoneal cavity and cytological analysis of the collected liquid. It allows detailed exploration of the peritoneal cavity and the description of the lesions.

Depending on the case, it is continued by a bilateral and omentectomie hystero-pelvic-oophorectomy (removal of the uterus, two fallopian tubes, two ovaries and omentum), noting the macroscopic characteristics of the tumor: adhesions, vegetation Etc. The most complete cytoreduction possible by avoiding being mutilative (resecting too much of the hail, definitive ostomy...), the aim being to achieve the absence of tumoral17 residue. Indeed the prognosis is directly correlated with the level of cytoréduction18. In the absence of a macroscopic tumor in the peritoneum, it is supplemented by biopsies of the pariétocoliques gutters, an exploration and biopsy of the diaphragmatic domes. It is accompanied by a resection of the suspected pelvic and retro-peritoneal adenopathies in the early stages (for full staging) or when a macroscopically complete resection of the lesions is envisaged. In the absence of an anomaly, the resection can be replaced by simple biopsies.

In strictly local cases and where there is a desire for pregnancy, a unilateral oophorectomy may be proposed, with the risk of underestimating the actual extension of the disease, which occurs in about one third of the cas19.

Early cytoreduction Intervention (or interval surgery)
This type of intervention is necessary for patients with an advanced stage in which an initial ' optimal ' intervention (leaving a residual disease) was not possible. The objective is to eliminate any macroscopic residual disease, if necessary using digestive resection (s).

Evaluation Intervention (or "second look")
It is intended to establish the response to initial chemotherapy and possibly to prepare intra-peritoneal treatment of consolidation. This intervention, whose impact on survival is debatable, cannot be systematic.
Metastatic stage Surgery
There is no consensus today on the surgical management of ovarian metastatic adenocarcinomas. Nevertheless, this surgery should be discussed in some patients, especially when the initial assessment suggests that it will be possible to practice the resection of all lesions VISIBLES20,21.

Medical
In ovarian cancer we talk about first-line or second-line chemotherapy.

First line chemotherapy is:

To adjuvant chemotherapy after complete surgery of a localized ovarian epithelial tumor;
To a first line of chemotherapy for a localized tumour (stages I to III) that is not operable or not extirpable. Interval surgery can be proposed after three cures in some patients;
A first line of chemotherapy in metastatic patients, preceded or not by surgery.
There is a global survival gain if a platinum salt is used in the first LIGNE22 chemotherapy. Cisplatin and carboplatin have equivalent efficacy with different toxicity profiles. The density of the platinum dose must be greater than 25 mg · m-2 per week.

The impact of paclitaxel on the front line remains uncertain. The studies of GOG23 and the European Organisation for the research and treatment of cancer are in favor of paclitaxel, the ICON324 study does not find this advantage. The SCOTROC test shows an equivalent efficacy between docetaxel-carboplatin and paclitaxel-carboplatin.

Anthracycline: The results are always controversial. There is no advantage in adding a anthracycline to a protocol that includes a taxane and a platinum salt.

Intra-peritoneal chemotherapy
Ovarian cancer is a disease that essentially evolves in the peritoneum. The idea of injecting chemotherapy directly into the peritoneal cavity is therefore appealing and was issued as early as 197825. There is a certain interest in this méthode26. Nevertheless the toxicity is severe with a significant degradation of the quality of life, and the technique remains complex, with possibles27 complications. This is not a very common procedure.

Consolidation chemotherapy
In patients with complete ovarian tumours who received complete chemotherapy (usually six cures of Taxol-carboplatin), the continuation of a consolidation chemotherapy was investigated. This consolidation chemotherapy seems to improve the survival time without relapse but does not improve overall survival. It has the drawbacks of extending the duration of treatment and increasing the toxicity of chemotherapy. This consolidation chemotherapy is therefore not a standard today.

Second-line chemotherapy
It corresponds to a second line of chemotherapy in a patient in progress during the first line of chemotherapy, or to a resumption of chemotherapy in the context of a recurrence after an initial treatment with curative, including a First-line chemotherapy.

It can be based on Cis-platinum with paclitaxel28 or gemcitabine29.

Other
Radiotherapy is little used in the management of ovarian cancer. In some exceptional conditions, radiation therapy can be used to reduce the size of a lesion that is responsible for compression.

Bevacizumab, a monoclonal antibody targeting angiogenesis, has some prometteurs30 results. The results of two phase III trials, GOG 218 and ICON7, where bevacizumab was used in the first line, in combination with the reference treatment (six cycles of Taxol carboplatin), are expected for 2010. These results could change the management of ovarian cancer in the front line.

Other targeted therapies are being evaluated in ovarian cancer but at less advanced research stages. Include:

Aflibercept is an analogue of the soluble receptors of VEGF.
Cediranib and pazopanib are multi-target tyrosine kinase inhibitors for which phase III trials are underway in relapsed ovarian cancer.
3-Déazaneplanocine has
Therapeutic Strategy
Limited stages (I and II)
The surgery consists of an initial laparotomy, supplemented by a hysterectomy, salpingo and bilateral oophorectomy. Conservative surgery can be discussed in a young woman willing to maternity.

Adjuvant chemotherapy is not useful in most stages I, the long-term prognosis being excellent31. Adjuvant chemotherapy:

Stages IA grade I: no adjuvant chemotherapy.
Stages IB, IC, IIA, IIB, IIC: Six cycles of a polychemotherapy based on platine32 salt, associated with a taxane or a anthracycline: PE3 or carboplatin-Taxol.
Stages III and IV
The surgical objective is to obtain a zero tumor residue without decaying surgery.

First-line chemotherapy is offered in the case of optimal initial resection (zero residue), based on six cycles of a polychemotherapy.

In the case of incomplete resection (macroscopic residue or greater than 1 cm), it is proposed to perform three cycles of chemotherapy with an early cytoreduction reintervention, followed by three new cycles of the same chemotherapy, alone or in combination With intra-peritoneal chemotherapy. The effectiveness of this plan remains controversée33,34.

Two randomized trials that showed an increase in survival with the early administration of intra-peritoneal chemotherapy, an intra-peritoneal catheter can be set up during early cytoreduction intervention when no longer exists of macroscopic residue (complete clinical response or complete resection of the tumor residue). Patients survive in 80% of cases.

Treatment of Relapse
The dosage of CA 125 is relevant for monitoring the evolution of Ovarian Cancer (ESMO 2005). A scanner is indicated in case of elevation of the CA 125. The elevation of this marker often indicates a relapse, with a bad prognosis, regardless of the treatment1.

Despite the correct initial support, the risk of relapse is important. At the relapse stage, it is rare to be able to offer curative treatment. The delay between relapse and the end of the initial chemotherapy is an essential parameter to guide the therapeutic strategy. The objective of the treatment is to prolong the survival and delay the complications associated with the disease. Anti-cancer therapy is mainly based on chemotherapy. There is little room for surgery in this context.

Supportive care (nutrition, pain, psychological support, palliative care) is an essential aspect of management.

Clinical and radiological Progression 6 months or more after the administration of platinum derivative: chemotherapy with platinum salt.
Clinical and radiological Progression less than 6 months after the administration of platinum derivative: other chemotherapy.
Isolated increase in CA 125 (asymptomatic, normal imaging): no treatment or tamoxifen 20 to 60 mg per day.
Isolated and unique peripheral ganglion Progression: surgical resection, more or less radiotherapy, and then surveillance.
Screening
It is difficult because giving only very little specific signs at the beginning. Interest is low, apart from high-risk patients, with no demonstrated influence on mortalité35.

In patients considered at high risk (carrying a mutation on the BRCA1 or BRCA2 gene), a regular examination by trans-vaginal ultrasound with dosage of the CA 125 marker is recommended from 35 years, or even sooner if there is a concept of form Family Précoce36. A systematic bilateral oophorectomy may be proposed in these if they are over 40 years of age and the absence of a child's desire

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