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1. Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: Results from an international multi-institutional study

Author

Cucinella, G, Schivardi, G, Zhou, X, Alhilli, M, Wallace, S, Wohlmuth, C, Baiocchi, G, Tokgozoglu, N, Raspagliesi, F, Buda, A, Zanagnolo, V, Zapardiel, I, Jagasia, N, Giuntoli, R, Glickman, A, Peiretti, M, Lanner, M, Chacon, E, Di Guilmi, J, Pereira, A, Laas-Faron, E, Fishman, A, Nitschmann, C, Kurnit, K, Moriarty, K, Joehlin-Price, A, Lees, B, Covens, A, De Brot, L, Taskiran, C, Bogani, G, Landoni, F, Grassi, T, Paniga, C, Multinu, F, De Vitis, L, Hernández, A, Mastroyannis, S, Ghoniem, K, Chiantera, V, Shahi, M, Fought, A, Mcgree, M, Mariani, A, Glaser, G, Cucinella G., Schivardi G., Zhou X. C., Alhilli M., Wallace S., Wohlmuth C., Baiocchi G., Tokgozoglu N., Raspagliesi F., Buda A., Zanagnolo V., Zapardiel I., Jagasia N., Giuntoli R., Glickman A., Peiretti M., Lanner M., Chacon E., Di Guilmi J., Pereira A., Laas-Faron E., Fishman A., Nitschmann C. C., Kurnit K., Moriarty K., Joehlin-Price A., Lees B., Covens A., De Brot L., Taskiran C., Bogani G., Landoni F., Grassi T., Paniga C., Multinu F., De Vitis L. A., Hernández A., Mastroyannis S., Ghoniem K., Chiantera V., Shahi M., Fought A. J., McGree M., Mariani A., Glaser G., Cucinella, G, Schivardi, G, Zhou, X, Alhilli, M, Wallace, S, Wohlmuth, C, Baiocchi, G, Tokgozoglu, N, Raspagliesi, F, Buda, A, Zanagnolo, V, Zapardiel, I, Jagasia, N, Giuntoli, R, Glickman, A, Peiretti, M, Lanner, M, Chacon, E, Di Guilmi, J, Pereira, A, Laas-Faron, E, Fishman, A, Nitschmann, C, Kurnit, K, Moriarty, K, Joehlin-Price, A, Lees, B, Covens, A, De Brot, L, Taskiran, C, Bogani, G, Landoni, F, Grassi, T, Paniga, C, Multinu, F, De Vitis, L, Hernández, A, Mastroyannis, S, Ghoniem, K, Chiantera, V, Shahi, M, Fought, A, Mcgree, M, Mariani, A, Glaser, G, Cucinella G., Schivardi G., Zhou X. C., Alhilli M., Wallace S., Wohlmuth C., Baiocchi G., Tokgozoglu N., Raspagliesi F., Buda A., Zanagnolo V., Zapardiel I., Jagasia N., Giuntoli R., Glickman A., Peiretti M., Lanner M., Chacon E., Di Guilmi J., Pereira A., Laas-Faron E., Fishman A., Nitschmann C. C., Kurnit K., Moriarty K., Joehlin-Price A., Lees B., Covens A., De Brot L., Taskiran C., Bogani G., Landoni F., Grassi T., Paniga C., Multinu F., De Vitis L. A., Hernández A., Mastroyannis S., Ghoniem K., Chiantera V., Shahi M., Fought A. J., McGree M., Mariani A., and Glaser G.

Abstract

Objective The prognostic significance of isolated tumor cells (<= 0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients.Methods Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods.Results 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space in

Published
2024

2. The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study

Author

Buda, A, Paniga, C, Taskin, S, Mueller, M, Zapardiel, I, Fanfani, F, Puppo, A, Casarin, J, Papadia, A, De Ponti, E, Grassi, T, Mauro, J, Turan, H, Vatansever, D, Gungor, M, Ortag, F, Imboden, S, Garcia-Pineda, V, Mohr, S, Siegenthaler, F, Perotto, S, Landoni, F, Ghezzi, F, Scambia, G, Taskiran, C, Fruscio, R, Buda A., Paniga C., Taskin S., Mueller M., Zapardiel I., Fanfani F., Puppo A., Casarin J., Papadia A., De Ponti E., Grassi T., Mauro J., Turan H., Vatansever D., Gungor M., Ortag F., Imboden S., Garcia-Pineda V., Mohr S., Siegenthaler F., Perotto S., Landoni F., Ghezzi F., Scambia G., Taskiran C., Fruscio R., Buda, A, Paniga, C, Taskin, S, Mueller, M, Zapardiel, I, Fanfani, F, Puppo, A, Casarin, J, Papadia, A, De Ponti, E, Grassi, T, Mauro, J, Turan, H, Vatansever, D, Gungor, M, Ortag, F, Imboden, S, Garcia-Pineda, V, Mohr, S, Siegenthaler, F, Perotto, S, Landoni, F, Ghezzi, F, Scambia, G, Taskiran, C, Fruscio, R, Buda A., Paniga C., Taskin S., Mueller M., Zapardiel I., Fanfani F., Puppo A., Casarin J., Papadia A., De Ponti E., Grassi T., Mauro J., Turan H., Vatansever D., Gungor M., Ortag F., Imboden S., Garcia-Pineda V., Mohr S., Siegenthaler F., Perotto S., Landoni F., Ghezzi F., Scambia G., Taskiran C., and Fruscio R.

Abstract

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Published
2023

3. The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study

Author

Buda, A., Paniga, C., Taskin, S., Mueller, M., Zapardiel, I., Fanfani, Francesco, Puppo, A., Casarin, J., Papadia, A., De Ponti, E., Grassi, T., Mauro, J., Turan, H., Vatansever, D., Gungor, M., Ortag, F., Imboden, S., Garcia-Pineda, V., Mohr, S., Siegenthaler, F., Perotto, S., Landoni, F., Ghezzi, F., Scambia, Giovanni, Taskiran, C., Fruscio, R., Fanfani F. (ORCID:0000-0003-1991-7284), Scambia G. (ORCID:0000-0003-2758-1063), Buda, A., Paniga, C., Taskin, S., Mueller, M., Zapardiel, I., Fanfani, Francesco, Puppo, A., Casarin, J., Papadia, A., De Ponti, E., Grassi, T., Mauro, J., Turan, H., Vatansever, D., Gungor, M., Ortag, F., Imboden, S., Garcia-Pineda, V., Mohr, S., Siegenthaler, F., Perotto, S., Landoni, F., Ghezzi, F., Scambia, Giovanni, Taskiran, C., Fruscio, R., Fanfani F. (ORCID:0000-0003-1991-7284), and Scambia G. (ORCID:0000-0003-2758-1063)

Abstract

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Published
2023

4. Oncologic and obstetric outcomes after simple conization for fertility-sparing surgery in FIGO 2018 stage IB1 cervical cancer

Author

Fanfani, F, Pedone Anchora, L, Di Martino, G, Bizzarri, N, Di Meo, M, Carbone, V, Paderno, M, Fedele, C, Paniga, C, Fagotti, A, Landoni, F, Scambia, G, Buda, A, Fanfani F., Pedone Anchora L., Di Martino G., Bizzarri N., Di Meo M. L., Carbone V., Paderno M., Fedele C., Paniga C., Fagotti A., Landoni F., Scambia G., Buda A., Fanfani, F, Pedone Anchora, L, Di Martino, G, Bizzarri, N, Di Meo, M, Carbone, V, Paderno, M, Fedele, C, Paniga, C, Fagotti, A, Landoni, F, Scambia, G, Buda, A, Fanfani F., Pedone Anchora L., Di Martino G., Bizzarri N., Di Meo M. L., Carbone V., Paderno M., Fedele C., Paniga C., Fagotti A., Landoni F., Scambia G., and Buda A.

Abstract

Objective Conization/simple trachelectomy is feasible in patients with early-stage cervical cancer. Retrospective data suggest that conization with negative lymph nodes could be a safe option for these patients. This study aims to provide oncologic and obstetric outcomes of a large series of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer managed by conization. Methods Patients with early cervical cancer and a desire to preserve fertility who underwent conization and pelvic lymphadenectomy from January 1993 to December 2019 in two Italian centers were included. Inclusion criteria were: age >18 years and ≤45 years, 2018 FIGO stage IB1, no prior irradiation or chemotherapy, absence of pre-operative radiologic evidence of nodal metastases, a strong desire to preserve fertility, and absence of concomitant malignancies. We excluded patients with confirmed infertility, neuroendocrine tumor, clear cell or mucinous carcinoma. Results A total of 42 patients were included. The median age was 32 years (range 19-44) and median tumor size was 11 mm (range 8-20). Squamous cell carcinoma was found in 27 (64.3%). Grade 3 tumor was present in 7 (16.7%) patients and lymphovascular space involvement was detected in 15 (35.7%). At a median follow-up of 54 months (range 1-185), all patients were alive without evidence of disease. In the entire series three patients experienced recurrence resulting in an overall recurrence rate of 7.1%. All the recurrences occurred in the pelvis (2 in the cervix and 1 in the lymph nodes), resulting in a 3-year disease-free survival of 91.6%. Twenty-two (52%) patients tried to conceive; 18 pregnancies occurred in 17 patients and 12 live births were reported (6 pre-term and 6 term pregnancies). Two miscarriages were recorded, one first trimester and one second trimester fetal loss. Conclusions Our study showed that conization is feasible for the conservative management of women with stage IB1 cer

Published
2021

6. Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case-control study

Author

Sina, F, Cassani, C, Comerio, C, De Ponti, E, Zanellini, F, Delle Marchette, M, Roversi, G, Jaconi, M, Arbustini, E, Urtis, M, Dell'Oro, C, Zambetti, B, Paniga, C, Acampora, E, Negri, S, Lazzarin, S, Cesari, S, Spinillo, A, Kotsopoulos, J, Fruscio, R, Sina, Federica, Cassani, Chiara, Comerio, Chiara, De Ponti, Elena, Zanellini, Francesca, Delle Marchette, Martina, Roversi, Gaia, Jaconi, Marta, Arbustini, Eloisa, Urtis, Mario, Dell'Oro, Cristina, Zambetti, Benedetta, Paniga, Cristiana, Acampora, Eleonora, Negri, Serena, Lazzarin, Sara, Cesari, Stefania, Spinillo, Arsenio, Kotsopoulos, Joanne, Fruscio, Robert, Sina, F, Cassani, C, Comerio, C, De Ponti, E, Zanellini, F, Delle Marchette, M, Roversi, G, Jaconi, M, Arbustini, E, Urtis, M, Dell'Oro, C, Zambetti, B, Paniga, C, Acampora, E, Negri, S, Lazzarin, S, Cesari, S, Spinillo, A, Kotsopoulos, J, Fruscio, R, Sina, Federica, Cassani, Chiara, Comerio, Chiara, De Ponti, Elena, Zanellini, Francesca, Delle Marchette, Martina, Roversi, Gaia, Jaconi, Marta, Arbustini, Eloisa, Urtis, Mario, Dell'Oro, Cristina, Zambetti, Benedetta, Paniga, Cristiana, Acampora, Eleonora, Negri, Serena, Lazzarin, Sara, Cesari, Stefania, Spinillo, Arsenio, Kotsopoulos, Joanne, and Fruscio, Robert

Abstract

OBJECTIVE: To describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls. METHODS: Consecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups. RESULTS: A total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006). CONCLUSION: We found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy.

Published
2022

7. EPV119/#397 Volume of nodal disease and oncologic outcomes in endometrial cancer patients with positive sentinel lymph nodes: an Italian multi-institutional study

Author

Martinelli, F, primary, Buda, A, additional, Fanfani, F, additional, Legge, F, additional, Roccio, M, additional, Falcone, F, additional, Perrone, AM, additional, Casarin, J, additional, Perutelli, A, additional, Biglia, N, additional, Scollo, P, additional, Romano, F, additional, Ditto, A, additional, Ferrari, D, additional, Monterossi, G, additional, Murgia, F, additional, Paniga, C, additional, Scambia, G, additional, and Raspagliesi, F, additional

Published
2021
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8. 252 Type of sentinel lymph nodes metastases and oncologic outcomes in endometrial cancer patients: an italian multi-institutional study

Author

Martinelli, F, primary, Buda, A, additional, Fanfani, F, additional, Legge, F, additional, Roccio, M, additional, Falcone, F, additional, Perrone, AM, additional, Casarin, J, additional, Perutelli, A, additional, Biglia, N, additional, Scollo, P, additional, Romano, F, additional, Ditto, A, additional, Ferrari, D, additional, Monterossi, G, additional, Murgia, F, additional, Paniga, C, additional, Scambia, G, additional, and Raspagliesi, F, additional

Published
2021
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9. 11 Oncologic outcomes and role of adjuvant therapy in endometrial cancer patients with low volume metastasis in the sentinel lymph nodes: an international multi-institutional study

Author

Ghoniem, K, primary, Dinoi, G, additional, Larish, A, additional, Zhou, X, additional, AlHilli, M, additional, Wallace, S, additional, Wohlmuth, C, additional, Baiocchi, G, additional, Tokgozoglu, N, additional, Raspagliesi, F, additional, Buda, A, additional, Zanagnolo, V, additional, Zapardiel, I, additional, Jagasia, N, additional, Giuntoli, R, additional, Glickman, A, additional, Peiretti, M, additional, Lanner, M, additional, Chacon, E, additional, Di Guilmi, J, additional, Pereira, A, additional, Faron, E, additional, Fishman, A, additional, Nitschmann, C, additional, Parker, S, additional, Joehlin-Price, A, additional, Lees, B, additional, Covens, A, additional, De Brot, L, additional, Taskiran, C, additional, Bogani, G, additional, Paniga, C, additional, Multinu, F, additional, Hernandez-Gutierrez, A, additional, Weaver, AL, additional, McGree, ME, additional, and Mariani, A, additional

Published
2020
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10. The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study

Author

Buda, Alessandro, Paniga, Cristiana, Taskin, Salih, Mueller, Michael, Zapardiel, Ignacio, Fanfani, Francesco, Puppo, Andrea, Casarin, Jvan, Papadia, Andrea, De Ponti, Elena, Grassi, Tommaso, Mauro, Jessica, Turan, Hasan, Vatansever, Dogan, Gungor, Mete, Ortag, Firat, Imboden, Sara, Garcia-Pineda, Virginia, Mohr, Stefan, Siegenthaler, Franziska, Perotto, Stefania, Landoni, Fabio, Ghezzi, Fabio, Scambia, Giovanni, Taskiran, Cagatay, Fruscio, Robert, Buda, A, Paniga, C, Taskin, S, Mueller, M, Zapardiel, I, Fanfani, F, Puppo, A, Casarin, J, Papadia, A, De Ponti, E, Grassi, T, Mauro, J, Turan, H, Vatansever, D, Gungor, M, Ortag, F, Imboden, S, Garcia-Pineda, V, Mohr, S, Siegenthaler, F, Perotto, S, Landoni, F, Ghezzi, F, Scambia, G, Taskiran, C, and Fruscio, R

Subjects
endometrial cancer, low-volume metastasis, sentinel lymph node biopsy, ultrastaging, recurrence-free survival, Cancer Research, Oncology, low-volume metastasi, 610 Medicine & health
Abstract

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Published
2023
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11. Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case-control study

Author

Marta Jaconi, Joanne Kotsopoulos, Chiara Comerio, Francesca Zanellini, Mario Urtis, Eloisa Arbustini, Arsenio Spinillo, Stefania Cesari, Martina Delle Marchette, Sara Lazzarin, Elena De Ponti, Eleonora Acampora, Benedetta Zambetti, Gaia Roversi, Chiara Cassani, Serena Negri, Cristina Dell'Oro, Cristiana Paniga, Federica Sina, Robert Fruscio, Sina, F, Cassani, C, Comerio, C, De Ponti, E, Zanellini, F, Delle Marchette, M, Roversi, G, Jaconi, M, Arbustini, E, Urtis, M, Dell'Oro, C, Zambetti, B, Paniga, C, Acampora, E, Negri, S, Lazzarin, S, Cesari, S, Spinillo, A, Kotsopoulos, J, and Fruscio, R

Subjects
Mutation, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Case-control study, Obstetrics and Gynecology, Serous Tubal Intraepithelial Carcinoma, medicine.disease_cause, Malignancy, medicine.disease, BRCA2 Protein, ovarian disease, Gastroenterology, Germline, Oncology, gynecologic surgical procedure, Internal medicine, medicine, BRCA2 protein, business, BRCA1 protein, Tamoxifen, medicine.drug, Genetic testing
Abstract

ObjectiveTo describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls.MethodsConsecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups.ResultsA total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006).ConclusionWe found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy.

Published
2022

12. Oncologic and obstetric outcomes after simple conization for fertility-sparing surgery in FIGO 2018 stage IB1 cervical cancer

Author

Nicolò Bizzarri, Giovanni Scambia, Maria Letizia Di Meo, Luigi Pedone Anchora, Camilla Fedele, Giampaolo Di Martino, Vittoria Carbone, Alessandro Buda, Fabio Landoni, Francesco Fanfani, Anna Fagotti, Mariachiara Paderno, Cristiana Paniga, Fanfani, F, Pedone Anchora, L, Di Martino, G, Bizzarri, N, Di Meo, M, Carbone, V, Paderno, M, Fedele, C, Paniga, C, Fagotti, A, Landoni, F, Scambia, G, and Buda, A

Subjects
Infertility, Adult, medicine.medical_specialty, Pregnancy Rate, cervical cancer, media_common.quotation_subject, Trachelectomy, Conization, Uterine Cervical Neoplasms, Fertility, Cervix Uteri, Pregnancy, Medicine, Mucinous carcinoma, Humans, Stage (cooking), Prospective cohort study, Cervix, media_common, Neoplasm Staging, Retrospective Studies, Cervical cancer, business.industry, Obstetrics, Obstetrics and Gynecology, Fertility Preservation, medicine.disease, Settore MED/40 - GINECOLOGIA E OSTETRICIA, medicine.anatomical_structure, Oncology, Concomitant, Carcinoma, Squamous Cell, Lymph Node Excision, Female, business
Abstract

ObjectiveConization/simple trachelectomy is feasible in patients with early-stage cervical cancer. Retrospective data suggest that conization with negative lymph nodes could be a safe option for these patients. This study aims to provide oncologic and obstetric outcomes of a large series of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer managed by conization.MethodsPatients with early cervical cancer and a desire to preserve fertility who underwent conization and pelvic lymphadenectomy from January 1993 to December 2019 in two Italian centers were included. Inclusion criteria were: age >18 years and ≤45 years, 2018 FIGO stage IB1, no prior irradiation or chemotherapy, absence of pre-operative radiologic evidence of nodal metastases, a strong desire to preserve fertility, and absence of concomitant malignancies. We excluded patients with confirmed infertility, neuroendocrine tumor, clear cell or mucinous carcinoma.ResultsA total of 42 patients were included. The median age was 32 years (range 19–44) and median tumor size was 11 mm (range 8–20). Squamous cell carcinoma was found in 27 (64.3%). Grade 3 tumor was present in 7 (16.7%) patients and lymphovascular space involvement was detected in 15 (35.7%). At a median follow-up of 54 months (range 1–185), all patients were alive without evidence of disease. In the entire series three patients experienced recurrence resulting in an overall recurrence rate of 7.1%. All the recurrences occurred in the pelvis (2 in the cervix and 1 in the lymph nodes), resulting in a 3-year disease-free survival of 91.6%. Twenty-two (52%) patients tried to conceive; 18 pregnancies occurred in 17 patients and 12 live births were reported (6 pre-term and 6 term pregnancies). Two miscarriages were recorded, one first trimester and one second trimester fetal loss.ConclusionsOur study showed that conization is feasible for the conservative management of women with stage IB1 cervical cancer desiring fertility. Oncologic outcomes appear favorable in this series of patients. Future prospective studies will hopefully provide further insight into this important question.

Published
2021

13. Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study.

Author

Cucinella G, Schivardi G, Zhou XC, AlHilli M, Wallace S, Wohlmuth C, Baiocchi G, Tokgozoglu N, Raspagliesi F, Buda A, Zanagnolo V, Zapardiel I, Jagasia N, Giuntoli R, Glickman A, Peiretti M, Lanner M, Chacon E, Di Guilmi J, Pereira A, Laas-Faron E, Fishman A, Nitschmann CC, Kurnit K, Moriarty K, Joehlin-Price A, Lees B, Covens A, De Brot L, Taskiran C, Bogani G, Landoni F, Grassi T, Paniga C, Multinu F, De Vitis LA, Hernández A, Mastroyannis S, Ghoniem K, Chiantera V, Shahi M, Fought AJ, McGree M, Mariani A, and Glaser G

Subjects
Female, Humans, Neoplasm Recurrence, Local pathology, Prognosis, Retrospective Studies, Middle Aged, Aged, Endometrial Neoplasms pathology, Sentinel Lymph Node pathology, Sentinel Lymph Node Biopsy
Abstract

Objective: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients., Methods: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods., Results: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion., Conclusions: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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14. Uterine venous malformations in the puerperium: 2 Atypical cases and literature review.

Author

Damiani GR, Dellino M, Cascardi E, Xuamin H, Di Gennaro D, Vimercati A, Vitagliano A, Malvasi A, Loizzi V, Paniga C, Lanteri L, Alfonso R, Cicinelli E, and Pellegrino A

Abstract

Uterine arteriovenous malformations (AVMs) is a rare but high-risk cause of uterine bleeding. The clinical management of this condition is challenging, as the ultrasound picture can sometimes be unambiguously interpreted. Moreover, in the puerperium in which acquired AVMs are most frequently formed, it is necessary to discuss the correct management in a multidisciplinary and personalized manner. We present two cases of AVMs developing in the puerperium, both with a vaginal delivery and spontaneous and complete secondment. The symptom of onset was an episode of bright red blood loss in the puerperium, on the 14th and 21st postpartum days, respectively. Transvaginal ultrasound showed a hypervascularized lesion in the myometrium with turbulent vascular flow, confirmed by transabdominal ultrasound and angiography. To date, there are no guidelines on the management of MAVs. In our cases we opted for a conservative approach, in order to preserve the fertility of the patient. These experiences reported have the purpose of enriching a literature still sparse on the subject and in the future to be able to represent a fulcrum for official recommendations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© 2023 The Authors.)

Published
2023
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15. The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study.

Author

Buda A, Paniga C, Taskin S, Mueller M, Zapardiel I, Fanfani F, Puppo A, Casarin J, Papadia A, De Ponti E, Grassi T, Mauro J, Turan H, Vatansever D, Gungor M, Ortag F, Imboden S, Garcia-Pineda V, Mohr S, Siegenthaler F, Perotto S, Landoni F, Ghezzi F, Scambia G, Taskiran C, and Fruscio R

Abstract

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Published
2023
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16. Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case-control study.

Author

Sina F, Cassani C, Comerio C, De Ponti E, Zanellini F, Delle Marchette M, Roversi G, Jaconi M, Arbustini E, Urtis M, Dell'Oro C, Zambetti B, Paniga C, Acampora E, Negri S, Lazzarin S, Cesari S, Spinillo A, Kotsopoulos J, and Fruscio R

Subjects
Adult, Aged, Case-Control Studies, Cystadenocarcinoma, Serous, Female, Humans, Middle Aged, Ovarian Neoplasms prevention & control, Fallopian Tubes pathology, Genes, Tumor Suppressor, Ovarian Neoplasms genetics, Prophylactic Surgical Procedures, Salpingo-oophorectomy
Abstract

Objective: To describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls., Methods: Consecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups., Results: A total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006)., Conclusion: We found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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17. Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

Author

Ghoniem K, Larish AM, Dinoi G, Zhou XC, Alhilli M, Wallace S, Wohlmuth C, Baiocchi G, Tokgozoglu N, Raspagliesi F, Buda A, Zanagnolo V, Zapardiel I, Jagasia N, Giuntoli R 2nd, Glickman A, Peiretti M, Lanner M, Chacon E, Di Guilmi J, Pereira A, Laas E, Fishman A, Nitschmann CC, Parker S, Joehlin-Price A, Lees B, Covens A, De Brot L, Taskiran C, Bogani G, Paniga C, Multinu F, Hernandez-Gutierrez A, Weaver AL, McGree ME, and Mariani A

Subjects
Aged, Carcinoma, Endometrioid pathology, Carcinoma, Endometrioid therapy, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplasm Staging, Treatment Outcome, Endometrial Neoplasms pathology, Endometrial Neoplasms therapy, Neoplasm Recurrence, Local pathology, Sentinel Lymph Node pathology
Abstract

Objective: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs)., Methods: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded., Results: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months)., Conclusions: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup., Competing Interests: Declaration of Competing Interest The authors confirm there are no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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18. Oncologic and obstetric outcomes after simple conization for fertility-sparing surgery in FIGO 2018 stage IB1 cervical cancer.

Author

Fanfani F, Pedone Anchora L, Di Martino G, Bizzarri N, Di Meo ML, Carbone V, Paderno M, Fedele C, Paniga C, Fagotti A, Landoni F, Scambia G, and Buda A

Subjects
Adult, Conization, Female, Humans, Neoplasm Staging, Pregnancy, Pregnancy Rate, Retrospective Studies, Carcinoma, Squamous Cell surgery, Cervix Uteri surgery, Fertility Preservation methods, Lymph Node Excision methods, Trachelectomy methods, Uterine Cervical Neoplasms surgery
Abstract

Objective: Conization/simple trachelectomy is feasible in patients with early-stage cervical cancer. Retrospective data suggest that conization with negative lymph nodes could be a safe option for these patients. This study aims to provide oncologic and obstetric outcomes of a large series of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer managed by conization., Methods: Patients with early cervical cancer and a desire to preserve fertility who underwent conization and pelvic lymphadenectomy from January 1993 to December 2019 in two Italian centers were included. Inclusion criteria were: age >18 years and ≤45 years, 2018 FIGO stage IB1, no prior irradiation or chemotherapy, absence of pre-operative radiologic evidence of nodal metastases, a strong desire to preserve fertility, and absence of concomitant malignancies. We excluded patients with confirmed infertility, neuroendocrine tumor, clear cell or mucinous carcinoma., Results: A total of 42 patients were included. The median age was 32 years (range 19-44) and median tumor size was 11 mm (range 8-20). Squamous cell carcinoma was found in 27 (64.3%). Grade 3 tumor was present in 7 (16.7%) patients and lymphovascular space involvement was detected in 15 (35.7%). At a median follow-up of 54 months (range 1-185), all patients were alive without evidence of disease. In the entire series three patients experienced recurrence resulting in an overall recurrence rate of 7.1%. All the recurrences occurred in the pelvis (2 in the cervix and 1 in the lymph nodes), resulting in a 3-year disease-free survival of 91.6%. Twenty-two (52%) patients tried to conceive; 18 pregnancies occurred in 17 patients and 12 live births were reported (6 pre-term and 6 term pregnancies). Two miscarriages were recorded, one first trimester and one second trimester fetal loss., Conclusions: Our study showed that conization is feasible for the conservative management of women with stage IB1 cervical cancer desiring fertility. Oncologic outcomes appear favorable in this series of patients. Future prospective studies will hopefully provide further insight into this important question., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2021
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