​Kembara Xtra - Medicine - Ovarian Cancer

​Kembara Xtra - Medicine - Ovarian Cancer 
Four percent of all cancers in women are ovarian cancer. Ovarian cancer is the most fatal of all gynecologic malignancies, accounting for 2.3% of all cancer fatalities nationally, and there are about 19,000 new cases and 14,000 deaths of it each year in the United States, per the CDC.


Cancer that develops in the ovary's epithelium (90–95%), sex cord stroma (5-8%), or germ cells (5%) as well as cancers that have spread to the ovary. The following are examples of histologic types:
Serous (most prevalent, 70–80%), mucinous, endometrioid, and clear cell are epithelial.
Sex cord stromal: Sertoli-Leydig granulosa
Egg yolk sac, teratoma, and dysgerminoma are examples of germ cells.
 Melanoma, lymphoma, and GI (Krukenberg, colon) cancers that metastasize

The majority of ovarian cancer cases are discovered at an advanced stage, with the average age of diagnosis being 63 years for epithelial cancer, 50 years for sex cord stromal cancer, and 10 to 30 years for germ cell cancer. In 2018, there were 19,679 new cases and 13,748 deaths per year in the United States, representing 1.1% of all new cancer cases.

Prevalence
Women have a 1-2% lifetime risk of acquiring ovarian cancer without a substantial family history or known genetic mutation, and in 2018, there were about 235,081 women living with the disease in the United States. Although inherited disorders may be responsible for 5–10% of ovarian cancer cases, most cases of ovarian cancer in the general population are random.

Pathophysiology and Etiology 
The biggest indicators include reproductive history and length of reproductive career (poor parity/infertility, early menarche, late menopause). By preventing repeated disturbance of the epithelial lining, suppression of ovulation may stop spontaneous mutations that reveal germline mutations.
● A higher percentage of ovarian cancers are now recognized to originate in the fallopian tube and other components of the secondary müllerian system, including primary peritoneal malignanciesthe geneticEarly-onset breast or ovarian cancer that is autosomal dominantly transmitted, has variable penetrance, and is typically accompanied by a BRCA-1 or BRCA-2 mutation10-14% of ovarian cancer patients have BRCA-1 or BRCA-2 mutations.Ovarian cancer lifetime risk with BRCA-1 is 39%, and with BRCA-2 is 11%.Increased risk for colorectal, endometrial, stomach, small intestinal, breast, pancreatic, and ovarian cancers as well as DNA mismatch repair gene defects are all features of Lynch syndrome, which is inherited autosomally and dominantly.Ovarian cancer lifetime risk for those with Lynch syndrome is 6–12.Risk factor: %90% of cases are sporadic, however family history is the biggest risk factor.Refer patients who have multiple relatives with breast or ovarian cancer to a genetic counselor.20–60% of those with familial cancer syndromes will develop ovarian cancer.Age, white race, nulligravidity, early menarche or late menopause, endometriosis, postmenopausal estrogen replacement medication, and living in an industrialized Western country are risk factors.It is debatable if fertility drugs raise the risk of ovarian cancer, although women with infertility who give birth to a healthy child do not have a higher risk of the disease.Obesity as a risk factor for ovarian cancer is still controversial, however some studies show indicate an increased risk with a BMI of 30 or higher and an increased fatality rate with a BMI of 35 or higher.General precautionsN Oral contraceptive use over a long period of time reduces risk by 50% after 15 years, and by 20% after 5 years.Salpingo-oophorectomy is a risk-reducing procedure that is projected to lower the incidence of BRCA-related gynecologic cancer by 96%. However, the protective impact of aspirin and NSAIDs in ovarian cancer is debatable.. High-risk (family history of a hereditary ovarian cancer condition) recommendations. population - Women should have transvaginal ultrasounds, CA-125 level measurements, and pelvic exams every six to twelve months starting at age 30 or ten years before the oldest age of diagnosis of ovarian cancer in the family. However, the usefulness of this strategy has not been proven.Women with premenopausal breast cancer or ovarian cancer in their families should be referred for genetic counseling.Prophylactic oophorectomy is indicated for mutation carriers by age 35 or after childbearing is finished.After preventative oophorectomy, the risk of primary peritoneal cancer is still 1-2%.No reliable ovarian cancer screening program is available for the general public.. - It is NOT advised to routinely test women of average risk with CA-125 and transvaginal US.Annual pelvic exams are possible, especially for postmenopausal women.Premenstrual females with an adnexal mass or postmenopausal females with a palpable adnexa should have further testing..

Pelvic discomfort, ascites, pleural effusion, carcinomatosis, intestinal obstruction, breast cancer, and endometrial cancer are all associated conditions.


Unspecific, generalized abdominal symptoms are the diagnosis.
Shortness of breath (pleural effusion) - Vomiting, nausea, and decreased oral intake (bowel blockage) - Acute presentation
- Shortness of breath and calf pain (venous thromboembolism)
- Excruciating pelvic or abdominal pain (ovarian torsion or rupture)
Presentation with subacute:
- Pelvic or abdominal pain or cramping
- Bloating, a feeling of fullness in the abdomen, and an increase in abdominal size (ascites)
- Anorexia, early satiety, and dyspepsia
- Dysparaneurism
- Urge or frequency of urination without infection
Fatigue, weight loss, and early puberty (germ cell or stromal tumors)

clinical assessment 
General appearance: cachexia, hirsutism (androgensecreting tumors) Pelvic: solid, irregular, fixed mass in the pelvis Rectovaginal: cul-de-sac nodularity Pulmonary: decreased breath sounds (pleural effusion) Lymphatics: lymphadenopathy Firm immobile enlarged lymph nodes (supraclavicular, inguinal)

Differential Diagnosis Benign reproductive tract conditions:
- Endometriomas - Physiologic cysts - Uterine fibroids
- Hydrosalpinx or a tubo-ovarian abscess - Pelvic inflammatory disease (PID)
 GI and endometrial cancers
IBS, diverticulitis, colitis, benign or borderline neoplasms, liver failure with ascites, and pelvic kidney

Laboratory Results 

Ovarian tissue pathology must be examined histologically in order to make the diagnosis of ovarian cancer.
Initial examinations (lab, imaging)
● CBC
To rule out hepatic disease, liver function tests (LFTs)
Tumor indicators, serum albumin, and urine analysis
- Cancers of the epithelium: CA-125, CA 19-9, and CEA
90% of women with malignant nonmucinous tumors had high CA-125 (normal 35 unit/dL). 50% of stage I ovarian tumors have CA-125 results that are mistakenly negative.
Elevations can be brought on by common benign gynecologic disorders such PID, endometriosis, fibroids, pregnancy, and menstruation. Non-gynecologic diseases include ascites, pleural effusion, congestive heart failure, pancreatitis, systemic lupus erythematosus, and liver illness can all cause an increase in CA-125 levels.
When it comes to mucinous tumors, CA 19-9 and CEA are stronger disease indicators and are useful if GI primary is suspected.
- Nonepithelial tumors include granulosa cell tumor, dysgerminoma, choriocarcinoma, and embryonal carcinoma caused by HCG, endodermal sinus tumor, and dysgerminoma caused by LDH.
To assess pelvic masses, transvaginal ultrasound is preferable to transabdominal ultrasound or computed tomography (CT): complicated masses (irregular boundaries, echogenic, septae).
 Contrast-enhanced CT of the abdomen and pelvis (to assess metastases and guide preoperative planning).
 CXR or CT chest (to check for lung nodules or pleural effusions)

Tests in the Future & Special Considerations
Patients with ovarian cancer should maintain their screening schedules for colonoscopies, Pap smears, and mammograms.
If a colonic primary is suspected, a colonoscopy (or other test to assess the colon) is required.


Other/Diagnostic Procedures

Don't biopsy ovarian lumps because you're worried about tumor seeding.
If the patient is not a candidate for surgery, consider paracentesis or thoracentesis (or an IR biopsy of the pelvic tumor).
- IR biopsy: The peritoneal surfaces of the pelvis and abdomen are frequently affected by epithelial ovarian cancer.
Interpretation of Tests
For a certain diagnosis, a pathologic diagnosis must be made (via surgery, an IR biopsy, or cytology).

Depending on the disease's stage, management strategies are chosen

General Actions 
It is essential to stage and debulk after a surgical examination.
Optimal tumor cytoreduction improves the efficacy of adjuvant therapy and is linked to a longer survival time.
It is possible to try neoadjuvant chemotherapy (NACT), preoperative chemotherapy, in patients with bulky advanced epithelial ovarian cancer where adequate cytoreduction with primary surgery is doubtful. This decision should be made after consulting with a gynecologic oncologist.


First Line of Medicine
Most patients will need chemotherapy or adjuvant therapy after surgery.
When staged optimally, patients in stages IA or IB and grades 1 or 2 don't need adjuvant therapy.
Adjuvant therapy is required for cancers with clear cell histology, grade 3 tumors, or tumors with stage IC or worse.
 Adjuvant chemotherapy for early-stage epithelial ovarian cancer consists of 6 cycles of carboplatin and paclitaxel (Taxol).
The DNA repair pathway of tumor cells is targeted by PARP inhibitors, which only affect tumor cells and spare normal ones.
typically used as maintenance therapy for platinum sensitivity or homologous recombination deficiency (HRD)-positive status; especially successful in BRCA-1 and BRCA-2 individuals
Cancers of the germ cells or the sex cord: bleomycin, etoposide, and cisplatin; chemotherapeutic contraindications: low functional condition, severe toxicity, hypersensitivity
 Unfavorable effects: Every regimen suppresses bone marrow. Ototoxicity, renal toxicity, and peripheral neuropathy have all been linked to cisplatin. Alopecia and neuropathy can be side effects of paclitaxel (Taxol).
Whenever possible, patients should be urged to take part in clinical trials.
Antiemetics include prochlorperazine (Compazine), ondansetron (Zofran), aprepitant (Emend), metoclopramide (Reglan), and promethazine (Phenergan).
Next Line
Topotecan, etoposide, bevacizumab, cyclophosphamide, tamoxifen, and doxorubicin liposomal (Doxil)

Additional Therapies Given the high risk of recurrence, patients with a known BRCA-1 or BRCA-2 mutation are put on the FDA-approved PARP inhibitor olaparib after completing primary treatment as maintenance therapy. If there is a good response to treatment, interval debulking surgery is then performed, followed by additional cycles of chemotherapy.


Surgical Procedures The best cytoreduction (less than 1 cm of maximum tumor diameter) is the goal of surgery.
 Epithelial cancer staging:
- Cytologic analysis of peritoneal fluid, including free fluid and peritoneal washings
- Complete hysterectomy, bilateral salpingo-oophorectomy, and tumor-reducing surgery
- Omentectomy - Peritoneal surface examination, palpation, and biopsy
- Adhesions and any suspicious locations should be biopsied.
- Appendectomy for mucinous tumors or if the appendix appears abnormal - Bilateral pelvic and para-aortic lymph node biopsies of the lymph nodes - Salpingooophorectomy (unilateral if only one ovary is involved) in young patients with germ cell or sex cord-stromal cancers for fertility-preserving care

Alternative Therapies 

Chemotherapy side effects like nausea, diarrhea, exhaustion, and hair loss may be lessened using CAM (complementary and alternative medicine) treatments include cognitive diversion, exercise, hypnosis, and relaxation. These, however, don't have sufficient data to support their actual efficacy.

Follow-Up Surgical patients should make an appointment for a follow-up visit within 4 weeks for postoperative evaluation and to continue treatment planning.
Patients receiving chemotherapy should visit the doctor frequently to monitor side effects and the course of their illness.
patient observation
 Physical examinations every two to four months during the first two years, every three to six months for the following three years, and then once a year.
Follow tumor marker levels after therapy to find recurrence if they were elevated at diagnosis. BMP and CBC as specified
 Physical examination and tumor indicators every three months during the first two years, then once a year, for germ cell/sex cord stromal.
- Due to the possibility of distant recurrences, tumor markers for sex cord-stromal malignancies should be evaluated every six months for ten years.
 When clinically necessary (i.e., recurrence is suspected), a CT scan of the chest, abdomen, and pelvis and/or a PET scan should be performed. Routine imaging monitoring is not advised.
EDUCATION OF PATIENTS
Patients need to be informed about the symptoms and indicators of recurrence, including as pelvic or abdominal pain or discomfort, bloating, and early fullness.

Recurrence rates for epithelial carcinoma in its early stages are 20%.
- >80% have advanced illness
 Based on SEER data from 2010 to 2016, 5-year survival rates for ovarian cancer (invasive epithelial)
- Ovary-specific localization: 92.6%
- Regional: 74.8% (spread to local lymph nodes).
- Distant (liver/lungs metastasized): 30.3%
 According to data from the International Federation of Gynecology and Obstetrics (FIGO), 5-year survival rates for ovarian cancer vary with stage.
A 90% B 86% C 83% of Stage I
A 78% B 73% of Stage II --
A 47% B 42% C 33% of Stage III
4% in Stage IV

Bowel blockage, mechanical obstruction, or carcinomatous ileus (frequently with recurrence) are complications. Other issues include malnutrition, electrolyte imbalances, fistula formation, pleural effusion, ascites, pseudomyxoma peritonei, and chemotherapy toxicity.

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