Ignite Creation Date:
2024-05-06 @ 2:22 AM
Last Modification Date:
2024-10-26 @ 11:18 AM
Study NCT ID:
NCT02039388
Status:
COMPLETED
Last Update Posted:
2022-09-02
First Post:
2014-01-16
Brief Title:
Lavage of the Uterine Cavity for the Diagnosis of Serous Tubal Intraepithelial Carcinoma
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
Pilot Study of the Lavage of the Uterine Cavity for the Diagnosis of Serous Tubal Intraepithelial Carcinoma
Status:
COMPLETED
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LUSTIC
Brief Summary:
The current study aims at answering the scientific question whether exfoliated cells from STICs get transported into the uterine cavity via the fallopian tube and whether it is possible to detect those cells in the lavage fluid from the uterine cavity and proximal fallopian tubes
To address this question the investigators will study 20 lavage samples and their 20 corresponding STIC-positive tissue samples in women who opt for risk-reducing bilateral salpingo-oophorectomy rrBSO because of increased risk of high grade serous carcinoma of the pelvis HGSC mostly carrying a BRCA mutation without a history of tubal occlusion for sterilization Women who opt to have the fallopian tubes removed but the ovaries preserved are eligible for the study too as are women who opt for rrBSO plus hysterectomy
To address this question the investigators will study 20 lavage samples and their 20 corresponding STIC-positive tissue samples in women who opt for risk-reducing bilateral salpingo-oophorectomy rrBSO because of increased risk of high grade serous carcinoma of the pelvis HGSC mostly carrying a BRCA mutation without a history of tubal occlusion for sterilization Women who opt to have the fallopian tubes removed but the ovaries preserved are eligible for the study too as are women who opt for rrBSO plus hysterectomy
Detailed Description:
The term high grade serous carcinoma HGSC describes a group of ovarian tubal and peritoneal cancers with an aggressive biological behavior HGSC is the leading cause of death from gynecologic malignancy in western civilized countries Women affected usually have advanced stage disease with metastatic spread throughout the abdominal cavity at time of diagnosis Five-year survival rates are in the range of 10 to 30 percent The specificity of current diagnostic tools CA-125 and transvaginal ultrasonography is low and ineffective at detecting HGSC early enough to improve clinical outcomes Definitive diagnosis of HGSC mostly relies on surgical confirmation These findings underline the need for an effective test for early detection of HGSC In the general population the lifetime risk is 15 percent
Women with germ line mutations in the BRCA1 and BRCA2 gene or a strong family history of epithelial ovarian cancer carry a high risk for breast cancer andor HGSC development Familial or inherited syndromes account for approximately 13 percent of cases of invasive epithelial ovarian and fallopian tube cancer The lifetime risk of ovarian cancer is 35 to 46 percent in women with BRCA1 gene mutations and 13 to 23 percent in those with BRCA2 mutations Again even in this population with high-risk for HGSC the specificity of CA-125 and transvaginal ultrasonography is still too low and ineffective to improve clinical outcomes
Over the last years increasing scientific evidence conglomerated that a large proportion of not only familial HGSC develop primarily in the lining of the fallopian tube that resembles Müllerian epithelium These precursor lesions are called serous tubal intraepithelial carcinomas STICs and are characterized by p53 overexpression on immunohistochemistry and high Ki-67 labelling index indicating a high proliferation index In over 90 percent STICs carry mutations in the TP53 tumor suppressor gene
As for today risk reducing bilateral salpingo-oophorectomy rrBSO is the most effective approach to reducing the risk of HGSC in high risk women Among women with an increased risk of HGSC most with BRCA mutations who underwent rrBSO 4 to 17 percent are found to have a STIC or even invasive neoplasm and approximately 80 percent of these neoplasms are in the ampullar part of the fallopian tube
Recent findings highlighted the malignant potential of STICs On histopathological specimen intraluminal shedding of tumor cells from STICs can be frequently demonstrated in the fallopian tube This shedding of tumor cells from STICs appears to be a risk factor for early transperitoneal metastasis frequently found in HGSC There is a strong clinical need for screening for STICs since they are the precursor lesion of HGSC These facts underline the importance of an effective - non-invasive - test for early detection of STICs
The ovarian surface the fallopian tubes the uterine cavity and the peritoneal cavity all together form a communicating compartment The physiological function of the ciliated lining of the tubes is to transport the egg into the uterine cavity after ovulation thus making it likely that exfoliated cells from STICs can be found in the uterine cavity
A promising approach for the detection of STICs has been established by Paul Speiser and Robert Zeillinger Molecular Oncology Group Department of General Gynaecology and Gynaecologic Oncology Medical University of Vienna Austria This approach is called the ALPINE technique Austrian Lavage Procedure for the Detection of tubal Intraepithelial Neoplasms manuscript under preparation To facilitate an quick and easy lavage of the uterine cavity and proximal tubes a special catheter was developed MEDICOPLAST MF 13005 catheter for uterine and tubal lavage The ALPINE technique includes a lavage of the uterine cavity and proximal fallopian tubes and subsequent analysis of this lavage fluid for the presence of pre-malignant and malignant cells
For the proof of principle that tumor cells from ovarian cancer are shed and can be found in the lavages of the uterine cavity uterine lavages were collected before a surgical intervention for suspected ovarian malignancy at our institution and at the Catholic University Leuven Division Gynaecological Oncology Belgium After malignancy was confirmed genetic changes in the TP53 and KRAS genes were determined in tumor tissue In a set of 9 epithelial ovarian cancer patients EOC and 1 ovarian metastases of a signet ring carcinoma the presence of these genetic changes was examined in lavage samples using digital droplet PCR ddPCR 10 genetic changes were identified in tumor tissue of these patients and 910 90 of these changes were detected in the corresponding lavage specimen too
Furthermore a filter approach followed by p53 immunofluorescence staining was established confirming the presence of tumor cells in the lavage sample of one additional patient
In a next step lavage samples of 23 ovarian carcinoma patients and if applicable corresponding tumor tissue were analysed through deep sequencing by the group of Bert Vogelstein Johns Hopkins University Baltimore USA The presence of genetic changes indicative for ovarian cancer could be confirmed in 1823 783 lavage specimen including both early and advanced stages
These results are proof that ovarian cancer cells are shed into the fallopian tubes and uterine cavity and can be collected through our ALPINE technique The fact that ovarian cancer cells were detected with high sensitivity in the lavage of the uterine cavity and proximal tubes shows that this approach has potential in early diagnosis Therefore the investigators are confident that this method could be applied in detection of premalignant changes in high risk patients as well
Aim of the study
The current study aims at answering the scientific question whether exfoliated cells from STICs get transported into the uterine cavity via the fallopian tube and whether it is possible to detect those cells in the lavage fluid from the uterine cavity and proximal fallopian tubes
Methods
To address this question the investigators will study 20 lavage samples and their 20 corresponding STIC-positive tissue samples in women who opt for rrBSO because of increased risk of HGSC mostly carrying a BRCA mutation without a history of tubal occlusion for sterilization Women who opt to have the fallopian tubes removed but the ovaries preserved are eligible for the study too as are women who opt for rrBSO plus hysterectomy
Women with germ line mutations in the BRCA1 and BRCA2 gene or a strong family history of epithelial ovarian cancer carry a high risk for breast cancer andor HGSC development Familial or inherited syndromes account for approximately 13 percent of cases of invasive epithelial ovarian and fallopian tube cancer The lifetime risk of ovarian cancer is 35 to 46 percent in women with BRCA1 gene mutations and 13 to 23 percent in those with BRCA2 mutations Again even in this population with high-risk for HGSC the specificity of CA-125 and transvaginal ultrasonography is still too low and ineffective to improve clinical outcomes
Over the last years increasing scientific evidence conglomerated that a large proportion of not only familial HGSC develop primarily in the lining of the fallopian tube that resembles Müllerian epithelium These precursor lesions are called serous tubal intraepithelial carcinomas STICs and are characterized by p53 overexpression on immunohistochemistry and high Ki-67 labelling index indicating a high proliferation index In over 90 percent STICs carry mutations in the TP53 tumor suppressor gene
As for today risk reducing bilateral salpingo-oophorectomy rrBSO is the most effective approach to reducing the risk of HGSC in high risk women Among women with an increased risk of HGSC most with BRCA mutations who underwent rrBSO 4 to 17 percent are found to have a STIC or even invasive neoplasm and approximately 80 percent of these neoplasms are in the ampullar part of the fallopian tube
Recent findings highlighted the malignant potential of STICs On histopathological specimen intraluminal shedding of tumor cells from STICs can be frequently demonstrated in the fallopian tube This shedding of tumor cells from STICs appears to be a risk factor for early transperitoneal metastasis frequently found in HGSC There is a strong clinical need for screening for STICs since they are the precursor lesion of HGSC These facts underline the importance of an effective - non-invasive - test for early detection of STICs
The ovarian surface the fallopian tubes the uterine cavity and the peritoneal cavity all together form a communicating compartment The physiological function of the ciliated lining of the tubes is to transport the egg into the uterine cavity after ovulation thus making it likely that exfoliated cells from STICs can be found in the uterine cavity
A promising approach for the detection of STICs has been established by Paul Speiser and Robert Zeillinger Molecular Oncology Group Department of General Gynaecology and Gynaecologic Oncology Medical University of Vienna Austria This approach is called the ALPINE technique Austrian Lavage Procedure for the Detection of tubal Intraepithelial Neoplasms manuscript under preparation To facilitate an quick and easy lavage of the uterine cavity and proximal tubes a special catheter was developed MEDICOPLAST MF 13005 catheter for uterine and tubal lavage The ALPINE technique includes a lavage of the uterine cavity and proximal fallopian tubes and subsequent analysis of this lavage fluid for the presence of pre-malignant and malignant cells
For the proof of principle that tumor cells from ovarian cancer are shed and can be found in the lavages of the uterine cavity uterine lavages were collected before a surgical intervention for suspected ovarian malignancy at our institution and at the Catholic University Leuven Division Gynaecological Oncology Belgium After malignancy was confirmed genetic changes in the TP53 and KRAS genes were determined in tumor tissue In a set of 9 epithelial ovarian cancer patients EOC and 1 ovarian metastases of a signet ring carcinoma the presence of these genetic changes was examined in lavage samples using digital droplet PCR ddPCR 10 genetic changes were identified in tumor tissue of these patients and 910 90 of these changes were detected in the corresponding lavage specimen too
Furthermore a filter approach followed by p53 immunofluorescence staining was established confirming the presence of tumor cells in the lavage sample of one additional patient
In a next step lavage samples of 23 ovarian carcinoma patients and if applicable corresponding tumor tissue were analysed through deep sequencing by the group of Bert Vogelstein Johns Hopkins University Baltimore USA The presence of genetic changes indicative for ovarian cancer could be confirmed in 1823 783 lavage specimen including both early and advanced stages
These results are proof that ovarian cancer cells are shed into the fallopian tubes and uterine cavity and can be collected through our ALPINE technique The fact that ovarian cancer cells were detected with high sensitivity in the lavage of the uterine cavity and proximal tubes shows that this approach has potential in early diagnosis Therefore the investigators are confident that this method could be applied in detection of premalignant changes in high risk patients as well
Aim of the study
The current study aims at answering the scientific question whether exfoliated cells from STICs get transported into the uterine cavity via the fallopian tube and whether it is possible to detect those cells in the lavage fluid from the uterine cavity and proximal fallopian tubes
Methods
To address this question the investigators will study 20 lavage samples and their 20 corresponding STIC-positive tissue samples in women who opt for rrBSO because of increased risk of HGSC mostly carrying a BRCA mutation without a history of tubal occlusion for sterilization Women who opt to have the fallopian tubes removed but the ovaries preserved are eligible for the study too as are women who opt for rrBSO plus hysterectomy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None