Using rADioMIcs and machine learning with ultrasonography for the differential diagnosis of myometRiAL tumors (the ADMIRAL pilot study). Radiomics and differential diagnosis of myometrial tumors.

OBJECTIVE: To develop and evaluate the performance of a radiomics and machine learning model applied to ultrasound (US) images in predicting the risk of malignancy of a uterine mesenchymal lesion. METHODS: Single-center retrospective evaluation of consecutive patients who underwent surgery for a malignant uterine mesenchymal lesion (sarcoma) and a control group of patients operated on for a benign uterine mesenchymal lesion (myoma). Radiomics was applied to US preoperative images according to the International Biomarker Standardization Initiative guidelines to create, validate and test a classification model for the differential diagnosis of myometrial tumors. The TRACE4 radiomic platform was used thus obtaining a full-automatic radiomic workflow. Definitive histology was considered as gold standard. Accuracy, sensitivity, specificity, AUC and standard deviation of the created classification model were defined. RESULTS: A total of 70 women with uterine mesenchymal lesions were recruited (20 with histological diagnosis of sarcoma and 50 myomas). Three hundred and nineteen radiomics IBSI-compliant features were extracted and 308 radiomics features were found stable. Different machine learning classifiers were created and the best classification system showed Accuracy 0.85 ± 0.01, Sensitivity 0.80 ± 0.01, Specificity 0.87 ± 0.01, AUC 0.86 ± 0.03. CONCLUSIONS: Radiomics applied to US images shows a great potential in differential diagnosis of mesenchymal tumors, thus representing an interesting decision support tool for the gynecologist oncologist in an area often characterized by uncertainty.

Bevacizumab as maintenance treatment in BRCA mutated patients with advanced ovarian cancer: A large, retrospective, multicenter case-control study.

OBJECTIVE: The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series. METHODS: This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status. RESULTS: Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22). CONCLUSIONS: No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS.

Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

The different impact of BRCA mutations on the survival of epithelial ovarian cancer patients: a retrospective single-center experience.

OBJECTIVES: The objective of this study was to examine whether the oncologic outcomes of BRCA1-associated and BRCA2-associated ovarian cancers correlate differently. METHODS: Genetic data and clinical characteristics were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Data from 147 BRCA-mutated patients (119 BRCA1-positive and 28 BRCA2-positive) were analyzed. At a median follow-up of 69 months, the median PFS was 27.2 and 45.46 months for BRCA1 and BRCA2 patients, respectively (p = 0.03). Median OS was 77.23 and 111.47 months for BRCA1 and BRCA2 patients, respectively (p = 0.08). CONCLUSION: BRCA2 mutations confer PFS and a trend to OS advantage compared with the BRCA1 mutation in BRCA-mutated epithelial ovarian cancer patients.

Response to treatment and prognostic significance of supradiaphragmatic disease in patients with high-grade serous ovarian cancer.

OBJECTIVES: This study was designed to investigate the response to chemotherapy of supradiaphragmatic disease diagnosed by preoperative imaging. As secondary objectives, oncologic outcomes of patients affected by supradiaphragmatic disease and their pattern of recurrence were also evaluated. METHODS: Data of consecutive patients with newly diagnosed FIGO stage IV (for supradiaphragmatic disease) epithelial ovarian cancer undergoing either primary debulking surgery or neoadjuvant chemotherapy plus interval debulking surgery between 2004 and 2021, were retrospectively collected. All patients were preoperatively evaluated by chest/abdominal CT scan or 18F-FDG PET/CT preoperatively and at follow-up to evaluate response to chemotherapy. At follow-up visits, site of recurrence diagnosed by imaging techniques was systematically recorded as it occurred. Progression-free and overall survival were measured by using Kaplan-Meier and Cox models. RESULTS: A total of 130 patients was included in this study with a median (range) follow-up of 32.9 (12.8-176.7) months. Complete or partial response was achieved in most of the patients after 3 cycles (77.7%) and 6 cycles (85.4%) of chemotherapy. At follow-up, recurrence occurred in 96 (73.8%) patients and the main site of recurrence was abdomen only in 64 (66.7%) patients. At multivariate analysis, residual disease after surgery was the only variable influencing survival outcomes. CONCLUSIONS: Supradiaphragmatic disease respond to chemotherapy in most patients affected by advanced EOC and recurrence mainly occurs in the abdomen. Results from this study confirms that abdominal optimal cytoreduction is the main surgical goal in the treatment of women affected by FIGO stage IV EOC.

Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: The experience of National Cancer Institute of Milan.

AIMS: We report the effects of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of advanced/recurrent epithelial ovarian cancer (EOC) on survival, morbidity and mortality. PATIENTS: Forty EOC patients were studied. Median age was 52.5 years (range: 30-68) and median follow-up 26.1 months (range: 0.3-117.6). Most patients presented advanced disease (stage III/IV). Previous systemic chemotherapy included cisplatin-based, taxol-based or taxol/platinum containing regimens. RESULTS: After the CRS, 33 patients presented no macroscopic residual disease. Five-year overall survival was 15%; the mean overall and progression-free survivals were 41.4 and 23.9 months, respectively. The morbidity, toxicity and mortality rates were 5%, 15% and 0%, respectively. CONCLUSION: Our results suggest that CRS + IPHP merits further evaluation by a formal prospective trial.

Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women.

OBJECTIVES: The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. METHODS: Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. RESULTS: Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. CONCLUSIONS: Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted.

Administration of recombinant human erythropoietin in patients with gynecological cancer before radical surgery.

UNLABELLED: The purpose of this prospective study was to investigate the efficacy of preoperative administration of recombinant human erythropoietin in patients with gynecological cancer. METHODS: The study included 38 women with gynecological cancer who were divided randomly in two groups. Study group A included 20 women with gynecological cancer who received recombinant human erythropoietin (rHuEPO) plus iron supplementation for ten days before surgery and five days postoperatively. Group B (controls) included 18 patients who received only iron supplementation for the same time period. Blood samples were obtained on days -10, -3, 0, +3, +5, +10. RESULTS: The mean hemoglobin level was significantly higher in group A than in group B on the day of the operation and remained significantly higher postoperatively while an inverse relationship was observed for mean ferritin values in the two groups. CONCLUSION: Preoperative administration of rHuEPO in patients with gynecological cancer seems to be effective in the blood management of these patients.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE: Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS: Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS: PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS: Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

Receptor status variation in primary breast cancer and subsequent accessible relapse.

To better understand the prognostic relevance of change in steroid receptor status, during the clinical course of breast cancer, we analysed the variation of estrogen and progesterone receptor (ER, PgR) status in a series of 532 primary tumors and metachronous accessible recurrences in individual patients. A more consistent variation was observed in patients with a receptor-positive primary (ER(+) or PgR(+)) than in those with a receptor-negative tumor (ER(-) or PgR(-)). Forty-four percent of PgR(+) and 24% of ER(+) tumors became negative, whereas only 20% of ER(-) or PgR(-) became positive. The changes were independent of tumor stage and menopausal status. However, steroid receptor variation appeared to be related to the interval between the primary tumor and relapse. In fact, the changes from ER(+) to ER(-) were more frequent in patients with a disease-free survival of less than 1 year, whereas changes from ER(-) to ER(+) occurred more often in patients with a disease-free survival of more than 3 years. Moreover, we observed a decrease in the number of ER(+) tumors following hormone treatment and a decrease in ER(-) tumors following chemotherapy. However, such variations did not reach statistical significance. Irrespective of the type of adjuvant therapy, the presence of at least one receptor (in particular, PgR) in the metachronous lesion was correlated with a long median time to relapse and to death. Our results confirmed the predictive relevance of receptor status of the primary lesion on relapse and survival and suggest the predictive relevance of receptor status of the metachronous lesion on post-relapse survival.

Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether pretreatment with metformin improves FSH-induced ovulation in women with clomiphene-resistant polycystic ovary syndrome (PCOS). DESIGN: Randomized prospective trial. SETTING: Department of Obstetrics and Gynecology, University of Siena. PATIENT(S): Twenty women with clomiphene citrate-resistant PCOS. INTERVENTION(S): The women were divided randomly into groups A and B (10 subjects each). Group B received 1,500 mg of metformin for at least a month before a single cycle of FSH stimulation. Group A underwent two cycles of FSH stimulation and then received metformin for a month before undergoing a third cycle. MAIN OUTCOME MEASURE(S): The number of FSH ampules, days of treatment, E2 level on the day of hCG, number of follicles > 15 mm, number of hyperstimulation, and the number of cycles with hCG withheld. RESULT(S): The number of follicles > 15 mm in diameter on the day of hCG administration was significantly lower in cycles performed after metformin treatment. The percentage of cycles with hCG withheld because of excessive follicular development was significantly lower in cycles treated with metformin. Plasma levels of E2 were significantly higher in cycles treated with FSH alone than in those treated with FSH and metformin. CONCLUSION(S): By reducing hyperinsulinism, metformin determines a reduction in intraovarian androgens. This leads to a reduction in E2 levels and favors orderly follicular growth in response to exogenous gonadotropins.

Outcome analysis of endoscopic sinus surgery in patients with nasal polyps and asthma.

OBJECTIVE: To investigate the efficacy of endoscopic sinus surgery (ESS) in the management of chronic sinusitis and asthma in patients with nasal polyps and steroid-dependent asthma. STUDY DESIGN: Retrospective chart review. METHODS: The study included 17 patients who underwent ESS with nasal polyps, steroid-dependent asthma with or without aspirin sensitivity and a minimum of 1 year postoperative follow-up. Nine patients were ASA sensitive, and eight patients were ASA tolerant. Chronic sinusitis and asthma were evaluated using subjective (patient complaints) and objective (computed tomography scans, pulmonary function tests, steroid doses) criteria. Preoperative data were compared with data obtained 12 to 18 months postESS. Tissue samples were graded for degree of inflammation and edema. RESULTS: Thirteen of the 17 (76.5%) patients reported improved clinical symptoms postESS. The postoperative Lund-Mackay scores were statistically lower for the 17 patients (P <.0001). The group experienced improvement in postoperative forced expiratory volume at 1 second (FEV1) (P <.014). Twelve of 17 (70.6%) experienced reduction in systemic steroid usage (P <.048). The ASA sensitive patients did not have a statistical improvement in postoperative FEV1 (P >.08) and sinonasal symptoms (P >.16) compared with the ASA tolerant group. Polyp tissue from the ASA sensitive patients demonstrated more edema and more inflammation on average than ASA tolerant polyps, but the results were not statistically significant. CONCLUSION: ESS demonstrates a beneficial effect on the sinonasal and asthma symptomatology in patients with nasal polyps and asthma using objective measures. Subset of aspirin-tolerant patients have statistically better outcome for sinonasal symptoms and pulmonary function testing than aspirin-sensitive patients.

Vitamin B12 levels in pregnancy influence erythropoietin response to anemia.

OBJECTIVE: to discover whether vitamin B12 levels influence erythropoietin (EPO) response during pregnancy. STUDY DESIGN: 117 pregnant women after the 27th week were divided into three groups according to log vitamin B12 concentrations. EPO (by enzyme-linked immunosorbent assay), Hemoglobin (Hb) and medium corpuscular Hb concentration (MCHC) were measured in these patients. The tests used were: calculation of simple statistic, regression coefficient and t-independent test with level of significance. An exclusive partitioned cluster method (K-means procedure) was used. RESULTS: For the lowest vitamin B12 levels there is an unexpected lack of difference in plasma EPO levels between anemic and nonanemic patients. In fact EPO levels were high even in nonanemic women. The only parameter of the blood count that seems to change in relation to vitamin B12 concentration is the MCHC. CONCLUSIONS: These results suggest that low vitamin B12 levels inhibit the suppression of EPO response in nonanemic pregnant women probably through MCHC modifications.

Surgical treatment of ovarian dermoid cysts.

OBJECTIVE: To evaluate the efficacy of laparoscopic ovarian cystectomy and to compare the surgical course, post-surgical course and particularly post-surgical pain of the laparoscopic and laparotomic methods. STUDY DESIGN: We conducted a surgical study on dermoid cysts at the Gynecology Department of Siena University between 1 January 1992 and 31 December 1996. The selected cases were randomized into two groups based on surgical approach: via laparotomy (n=22) or laparoscopy (n=22). Surgical times, estimated blood loss, post-surgical pain, time in hospital, speed of recovery and complications were compared. RESULTS: Mean blood loss was significantly less for laparoscopy (58.64+/-30.17 ml versus 103.84+/-38.45 ml, P<0.05). Mean hospitalization was 6.32+/-1.09 days for laparotomy and 3.18+/-0.39 days for laparoscopy (P<0.05). Post-surgical pain was significantly less in laparoscopy patients (P<0.05). The laparoscopic technique had fewer post-surgical complications. CONCLUSIONS: The laparoscopic approach had many advantages. Laparoscopy should be the elective treatment for women with dermoid cysts, because it has many advantages for the patient and lower costs for the national health system.

Total abdominal hysterectomy: a randomized study comparing two techniques.

BACKGROUND: Abdominal hysterectomy is the most frequent operation performed by gynecologists. The most commonly used techniques are intrafascial, extrafascial and supracervical hysterectomy; in our department we mainly use the first method. A variant of this technique, because during the operation we use only an Allis clamp, simplifies the operation and maintains certain anatomical relationships between neighbouring pelvic structures. METHODS: To compare two different surgical techniques between 1/1/1991 and 31/12/95, 262 women were randomized pre-operatively: 133 by the intrafascial technique of Richardson and 129 by the variant hysterectomy technique. The difference between the two techniques (Richardson versus variant hysterectomy technique), as performed in our department, was investigated regarding the clamping of uterine vessels, the resection of uterosacral and cardinal ligament. The two-tailed student test was used for continuous data and chi2 analysis for discrete data. RESULTS: Less blood loss occurred in the variant than in the Richardson group (P<0.01) and no intrasurgical complications occurred as compared to one case of ureter lesion in the Richardson group. There were no differences in the number of days of hospitalization. No particular post-surgical complications occurred in the follow-up period, which has now elapsed. After 36 months of follow-up the variant group showed a reduced incidence (not significant) of vaginal vault prolapse. The patients who underwent the variant hysterectomy technique reported better compliance with regard to sexual intercourse and urinary function than the Richardson group. CONCLUSION: We conclude that the variant hysterectomy technique is as valid as the Richardson technique, giving the surgeon the possibility of maintaining certain anatomical relationships between neighbouring pelvic structures. It also has minor delayed complications.

Association between cutaneous melanoma and neurofibromatosis type 1: analysis of three clinical cases and review of the literature.

The authors report a rare association between cutaneous melanoma and Von Recklinghausen's disease (NF-1) and analyze the possible meaning of this occurrence. Various types of tumors have been associated with NF-1, in particular those of neuroectodermal origin, such as malignant peripheral nerve sheath tumors (MPNST) and phaeochromocytoma. The development of malignant melanoma in NF-1 patients is rare. Data from the literature is enable to demonstrate an increased incidence of cutaneous melanoma in patients with neurofibromatosis but the association of these two disorders seems reasonable in theory, as both are abnormalities of a neural crest origin. The cases described may represent not only a clinical report of two rarely associated disorders, but may also confirm the biological mechanisms responsible for these infrequent diseases.

Sentinel node biopsy in patients with cutaneous melanoma of the head and neck.

Biopsy of head and neck sentinel nodes (SNs) can be technically problematic due to the unpredictable and variable drainage patterns of this anatomic region. The aim of the present study was to evaluate the feasibility of SN biopsy for cutaneous melanoma of the head and neck. We performed SN biopsy in 17 patients affected by stage I cutaneous melanoma of the head and neck on the basis of lymphoscintigraphy, blue dye and gamma probe. A total of 24 procedures were performed. Drainage to more than one lymphatic basin was observed in five patients (two basins in three cases and three basins in two cases) and in all cases SN biopsy was performed in all basins. The biopsy distribution by site was: six cervical nodes, five parotid nodes, four supraclavicular and submandibular nodes, three auricular and axillary nodes. The SN identification rate was 87.5% (21/24); metastases were discovered in four cases, with a positivity rate of 23.6%. At the time of writing, 1 patient is alive with local disease, 3 patients are dead and 13 are alive and free of disease with a follow-up ranging from 1 to 40 months (median, 21 months) following SN biopsy. In our opinion preoperative lymphoscintigraphy and the intraoperative use of a gamma probe are useful for the identification of lymphatic drainage of cutaneous melanoma of the head and neck.

Surgical treatment of gastric metastases from cutaneous melanoma: experience of the National Cancer Institute of Milan.

AIM: To evaluate the role of a surgical approach in patients affected with gastric metastases from cutaneous melanoma. METHODS: A retrospective review of our local melanoma database of 2100 patients identified 31 cases with gastric metastatic deposits. Nine of them were considered candidates for surgical resection. RESULTS: Median overall survival of the 9 patients who underwent surgery was 14.2 months. Six (67%) underwent a local radical resection of disease, and 3 (33%) had a simple exploratory laparotomy. The median survival was 21.6 months (range, 4-32 months) for the subset receiving radical surgery and 3.6 months (range, 2-6 months) for the patients who had no resection. Median follow-up was 14.2 months. No specific correlation of serologic LDH levels and final outcome, as documented elsewhere, was observed. A marked decreased or substantial remission of symptoms with an improvement in quality of life was observed in all radically resected patients. CONCLUSIONS: Patients with gastric metastases from melanoma may benefit from surgery if all macroscopic disease can be removed. In addition, gastric resection in patients with symptomatic melanoma spread to the stomach provides important symptomatic palliation.