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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Uterine adenosarcomas are typically treated with a total abdominal hysterectomy and bilateral salpingoophorectomy (TAH-BSO). Ovary sparing surgery may be done in women wishing to preserve fertility.
Uterine sarcoma are rare, out of all malignancies of the uterine body only about 4% will be uterine sarcomas. Generally, the cause of the lesion is not known, however patients with a history of pelvic radiation are at higher risk. Most tumors occur after menopause.
Women who take long-term tamoxifen are at higher risk.
The prognosis is determined primarily by the cancer stage. Most tumours are discovered at an early stage and have a good prognosis, especially when compared to uterine carcinosarcoma. Five year survival for stage I and stage III tumours is approximately 80% and 50% respectively.
Therapy is based on staging and patient condition and utilizes one or more of the following approaches.
Surgery is the mainstay of therapy if feasible involving total abdominal hysterectomy with bilateral salpingo-oophorectomy. Other approaches include radiation therapy, chemotherapy, and hormonal therapy.
Prognosis is relatively poor.
Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rate, even for metastatic gestational choriocarcinoma, is around 90–95%.
At present, treatment with single-agent methotrexate is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.
Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding.
Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers.
A malignant mixed Müllerian tumor, also known as malignant mixed mesodermal tumor, MMMT and carcinosarcoma, is a malignant neoplasm found in the uterus, the ovaries, the fallopian tubes and other parts of the body that contains both carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components. It is divided into two types, homologous (in which the sarcomatous component is made of tissues found in the uterus such as endometrial, fibrous and/or smooth muscle tissues) and a heterologous type (made up of tissues not found in the uterus, such as cartilage, skeletal muscle and/or bone). MMMT account for between two and five percent of all tumors derived from the body of the uterus, and are found predominantly in postmenopausal women with an average age of 66 years. Risk factors are similar to those of adenocarcinomas and include obesity, exogenous estrogen therapies, and nulliparity. Less well-understood but potential risk factors include tamoxifen therapy and pelvic irradiation.
Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy. In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.
Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).
The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.
A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.
Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, even though the unit treated more men with the worst prognosis.
Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers
The common treatment for phyllodes is wide local excision. Other than surgery, there is no cure for phyllodes, as chemotherapy and radiation therapy are not effective. The risk of developing local recurrence or metastases is related to the histologic grade, according to the above-named features. Despite wide excision, a very high percentage of surgeries yielded incomplete excision margins that required revision surgery. Radiation treatment after breast-conserving surgery with negative margins may significantly reduce the
local recurrence rate for borderline and malignant tumors. The authors of a 2012 study have derived a risk calculator for relapse risk of phyllodes tumors after surgery.
There is debate over the naming of MMMT; the term carcinosarcoma was formerly used to describe lesions with homologous tumors, and "malignant mixed Müllerian tumor" or "mixed mesodermal tumor" was used to describe heterologous tumors. While "carcinosarcoma" now considered standard, "malignant mixed Müllerian tumor" has a lengthy history within gynecological literature and is expected to continue to be used. The naming issue to a certain extent reflects histological characteristics and development of the tumors, in which the different types of tissues are believed to either develop separately and join into a single mass (the "collision" theory), that an adenocarcinoma stimulates the stroma to create a tumor (the "composition" theory), or that the tumor is the result of a stem cell that differentiates into different cell types (the "combination" theory). "Collision" tumors are normally easily recognized and not considered true MMMTs; the "combination" theory is most widely held, and is due to evidence that the tumors develop from a single line of cells, developing in a fashion similar to the fundus of the uterus from the Müllerian duct - first from a stem cell into a population of cells, that then differentiates into epithelial and stromal components.
There is evidence that some tumors are better explained by the composition theory, due to the aggressive nature of the epithelial cells involved which tend to metastasize much more readily than the sarcomal component. The behavior of MMMT overall is more related to the type and grade of the epithelium than the sarcoma, which suggests the sarcomal portion is an atypical "bystander" than primary driver of the tumor. Despite this, when purely endometrial tumors are compared to MMMTs, the MMMT tumor tends to have a worse prognosis.
Serous tumours are part of the surface epithelial-stromal tumour group of ovarian neoplasms, which derive from Mullerian epithelium.
They are common neoplasms with a strong tendency to bilaterality, and they account for 50% of all ovarian tumours.
Sixty percent are benign (cystadenoma), 10% are borderline and 30% are malignant (cystadenocarcinoma).
Phyllodes tumors are considered to be on a spectrum of disease that consists of fibroadenoma, fibroadenoma variant and benign phyllodes. Some would extend the spectrum to include malignant phyllodes tumors and frank sarcoma.
The primary method for treatment is surgical, not medical. Radiation and chemotherapy are not needed for benign lesions and are not effective for malignant lesions.
Benign granular cell tumors have a recurrence rate of 2% to 8% when resection margins are deemed clear of tumor infiltration. When the resection margins of a benign granular cell tumor are positive for tumor infiltration the recurrence rate is increased to 20%. Malignant lesions are aggressive and difficult to eradicate with surgery and have a recurrence rate of 32%.
Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta. It is characterized by "early hematogenous spread" to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also classified as a germ cell tumor and may arise in the testis or ovary.
Cervical cancers can recur with symptoms of vaginal bleeding and/or discharge, pelvic pain, pain in the back and legs, leg swelling (edema), chronic cough and weight loss. It can recur in the vagina, pelvis, lymph nodes, lung, or liver. “If radiation was not given previously, recurrences that are confined to the pelvis may be treated with external beam radiation with chemotherapy and intracavitary or interstitial radiation therapy. If radiation therapy was already given, the only option is the removal of the vagina, uterus, and the bladder and/or rectum with the creation of an artificial bladder-a pelvic exenteration. The five-year survival rate after a pelvic exenteration is about 50 percent.” (womenscancercenter.com) Chemotherapy is useful in women with recurrent tumors which cannot be removed surgically or in women with metastatic diseases. Chances of survival of chemotherapy, if diagnosed in early stage, is grater than 50%.
Carcinosarcomas are malignant tumors that consist of a mixture of carcinoma (or epithelial cancer) and sarcoma (or mesenchymal/connective tissue cancer). Carcinosarcomas are rare tumors, and can arise in diverse organs, such as the skin, salivary glands, lungs, the esophagus, pancreas, colon, uterus and ovaries.
Four main hypotheses have been proposed for the cellular origins of carcinosarcoma, based largely on the pathology of the disease. First, the collision tumor hypothesis, which proposes the collision of two independent tumors resulting in a single neoplasm, based on the observation that skin cancers and superficial malignant fibrous histiocytomas are commonly seen in patients with sun-damaged skin; second, the composition hypothesis, which suggests that the mesenchymal component represents a pseudosarcomatous reaction to the epithelial malignancy; third, the combination hypothesis, which suggests that both the epithelial and mesenchymal components of the tumor arise from a common pluripotential stem cell that undergoes divergent differentiation; and fourth, the conversion/divergence hypothesis, which argues that the sarcomatous component of the tumor represents a metaplastic sarcomatous transformation of the epithelial component. Despite the remaining uncertainty on the mechanisms that generate these tumors, recent immunohistochemical, ultrastructural, and molecular genetic studies suggest and favor the notion of monoclonality in carcinosarcoma. In addition, identical p53 and KRAS mutations have been identified in both epithelial and mesenchymal components of carcinosarcoma, findings that suggest an early alteration in the histogenesis of the tumor with late transformation or degeneration of the epithelial component into the sarcomatous component.
10-year survival rates for mucinous tumors is excellent in the absence of invasion.
In the case of borderline tumors confined to the ovary and malignant tumors without invasion, the survival rates are 90% or greater. In invasive mucinous cystadenocarcinomas, the survival is approximately 30%
Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium (modified peritoneum) or from endometrial or Fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment.
There are several experimental therapies for endometrial cancer under research, including immunologic, hormonal, and chemotherapeutic treatments. Trastuzumab (Herceptin), an antibody against the Her2 protein, has been used in cancers known to be positive for the Her2/neu oncogene, but research is still underway. Immunologic therapies are also under investigation, particularly in uterine papillary serous carcinoma.
Cancers can be analyzed using genetic techniques (including DNA sequencing and immunohistochemistry) to determine if certain therapies specific to mutated genes can be used to treat it. PARP inhibitors are used to treat endometrial cancer with PTEN mutations, specifically, mutations that lower the expression of PTEN. The PARP inhibitor shown to be active against endometrial cancer is olaparib. Research is ongoing in this area as of the 2010s.
Research is ongoing on the use of metformin, a diabetes medication, in obese women with endometrial cancer before surgery. Early research has shown it to be effective in slowing the rate of cancer cell proliferation. Preliminary research has shown that preoperative metformin administration can reduce expression of tumor markers. Long-term use of metformin has not been shown to have a preventative effect against developing cancer, but may improve overall survival.
Temsirolimus, an mTOR inhibitor, is under investigation as a potential treatment. Research shows that mTOR inhibitors may be particularly effective for cancers with mutations in PTEN. Ridaforolimus (deforolimus) is also being researched as a treatment for people who have previously had chemotherapy. Preliminary research has been promising, and a stage II trial for ridaforolimus was completed by 2013. There has also been research on combined ridaforolimus/progestin treatments for recurrent endometrial cancer. Bevacizumab and tyrosine kinase inhibitors, which inhibit angiogenesis, are being researched as potential treatments for endometrial cancers with high levels of vascular endothelial growth factor. Ixabepilone is being researched as a possible chemotherapy for advanced or recurrent endometrial cancer. Treatments for rare high-grade undifferentiated endometrial sarcoma are being researched, as there is no established standard of care yet for this disease. Chemotherapies being researched include doxorubicin and ifosfamide.
There is also research in progress on more genes and biomarkers that may be linked to endometrial cancer. The protective effect of combined oral contraceptives and the IUD is being investigated. Preliminary research has shown that the levonorgestrel IUD placed for a year, combined with 6 monthly injections of gonadotropin-releasing hormone, can stop or reverse the progress of endometrial cancer in young women. An experimental drug that combines a hormone with doxorubicin is also under investigation for greater efficacy in cancers with hormone receptors. Hormone therapy that is effective in treating breast cancer, including use of aromatase inhibitors, is also being investigated for use in endometrial cancer. One such drug is anastrozole, which is currently being researched in hormone-positive recurrences after chemotherapy. Research into hormonal treatments for endometrial stromal sarcomas is ongoing as well. It includes trials of drugs like mifepristone, a progestin antagonist, and aminoglutethimide and letrozole, two aromatase inhibitors.
Research continues into the best imaging method for detecting and staging endometrial cancer. In surgery, research has shown that complete pelvic lymphadenectomy along with hysterectomy in stage 1 endometrial cancer does not improve survival and increases the risk of negative side effects, including lymphedema. Other research is exploring the potential of identifying the sentinel lymph nodes for biopsy by injecting the tumor with dye that shines under infrared light. Intensity modulated radiation therapy is currently under investigation, and already used in some centers, for application in endometrial cancer, to reduce side effects from traditional radiotherapy. Its risk of recurrence has not yet been quantified. Research on hyperbaric oxygen therapy to reduce side effects is also ongoing. The results of the PORTEC 3 trial assessing combining adjuvant radiotherapy with chemotherapy were awaited in late 2014.
SCTs are very rare in adults, and as a rule these tumors are benign and have extremely low potential for malignancy. This estimation of potential is based on the idea that because the tumor existed for decades prior to diagnosis, without becoming malignant, it has little or no potential to ever become malignant. For this reason, and because coccygectomy in adults has greater risks than in babies, some surgeons prefer not to remove the coccyx of adult survivors of SCT. There are case reports of good outcomes.
Fertility subsequent to treatment of surface epithelial-stromal tumors depends mainly on histology and initial
staging to separate it into early borderline (or more benign) versus advanced stages of borderline (or more malignant). Conservative management (without bilateral oophorectomy) of early stage borderline tumors have been estimated to result in chance of over 50% of spontaneous pregnancy with a low risk of lethal recurrence of the tumor (0.5%). On the other hand, in cases of conservative treatment in advanced stage borderline tumors, spontaneous pregnancy rates have been estimated to be 35% and the risk of lethal recurrence 2%.
For malignant teratomas, usually, surgery is followed by chemotherapy.
Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy.
Ovarian tumors, or ovarian neoplasms, are tumors arising from the ovary. They can be benign or malignant (ovarian cancer).
Fibrosarcoma occurs most frequently in the mouth in dogs . The tumor is locally invasive, and often recurs following surgery . Radiation therapy and chemotherapy are also used in treatment. Fibrosarcoma is also a rare bone tumor in dogs.
In cats, fibrosarcoma occurs on the skin. It is also the most common vaccine-associated sarcoma. In 2014, Merial launched Oncept IL-2 in Europe for the management of such feline fibrosarcomas.
A Mixed tumor is a tumor that derives from multiple tissue types.
For example, a "Chondroid syringoma" is a cutaneous condition characterized histologically by nests of cuboidal or polygonal epithelial cells in the dermis.
There are two types: one derived from a single germ cell layer that differentiates into more than one cell type, and one derived from more than one germ cell layer (totipotent cells).