TP53 mutations and survival in ovarian carcinoma patients receiving first-line chemotherapy plus bevacizumab: Results of the MITO16A/MaNGO OV-2 study.

To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV-2 trial, a Phase IV study of chemotherapy combined with BEV in first-line treatment of advanced OC, we evaluated TP53 mutations by next-generation sequencing and p53 expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated TP53 mutations in terms of type, function, and site, and IHC data with patients' clinicopathological characteristics and survival. TP53 missense mutations of unknown function (named unclassified) represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival (OS) both in univariable (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.20-0.92, p = .03) and multivariable analysis (HR = 0.39, 95% CI = 0.18-0.86, p = .02). Concordance between TP53 mutational analysis and IHC was 91%. We observed an HR of 0.70 for OS in patients with p53 IHC overexpression compared to p53 wild-type, which however did not reach statistical significance (p = .31, 95% CI = 0.36-1.38). Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with OC receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated OC patients and deserve to be assessed for their potential predictive role in future randomized clinical studies.

Early non-compliance to ERAS in gynecological open surgery for malignancies, and post-operative complications: a multicenter, prospective, observational, cohort study.

BACKGROUND: Open surgical procedures for gynecological malignancies have a potential risk of post-operative complications and hence prolonged hospitalization, despite adherence to an Enhanced Recovery After Surgery (ERAS) protocol. PRIMARY OBJECTIVE: To investigate the relationship between non-compliance to an ERAS protocol in the post-operative setting and the rate of post-operative complications, in women who underwent open surgery for gynecological malignancies. STUDY HYPOTHESIS: Early non-compliance with the ERAS protocol increases the risk of post-operative complications. TRIAL DESIGN: Multicenter, prospective, observational, cohort study. MAJOR INCLUSION CRITERIA: Patients with histologically proven gynecological cancer (endometrial, uterine, tubo-ovarian, and cervical) undergoing elective open surgery and managed according to ERAS guidelines. EXCLUSION CRITERIA: Patients with post-operative recovery in an intensive care unit, undergoing anterior or total pelvic exenteration or intraperitoneal chemotherapy. Previous radiotherapy or previous non-gynecological major abdominal surgery. PRIMARY ENDPOINT: Association of non-compliance with the ERAS protocol using five selected indicators on post-operative day 2 with the rate of 30-day post-operative complications. SAMPLE SIZE: 600 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: At present, 106 patients have been recruited. Based on this, the accrual should be completed in 2025. Results should be presented at the end of 2025. TRIAL REGISTRATION: NCT05738902.

Hepatocellular carcinoma in pregnancy: A systematic review.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy. MATERIAL AND METHODS: We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584). RESULTS: We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%). CONCLUSIONS: Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.

Integrated mutational landscape analysis of uterine leiomyosarcomas.

Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and 27 from The Cancer Genome Atlas (TCGA). Among them, a total of 55 Yale samples including two patient-derived xenografts (PDXs) and 27 TCGA samples have whole-exome sequencing (WES) data; 10 Yale and 27 TCGA samples have RNA-sequencing (RNA-Seq) data; and 11 Yale and 10 TCGA samples have whole-genome sequencing (WGS) data. We found recurrent somatic mutations in TP53, MED12, and PTEN genes. Top somatic mutated genes included TP53, ATRX, PTEN, and MEN1 genes. Somatic copy number variation (CNV) analysis identified 8 copy-number gains, including 5p15.33 (TERT), 8q24.21 (C-MYC), and 17p11.2 (MYOCD, MAP2K4) amplifications and 29 copy-number losses. Fusions involving tumor suppressors or oncogenes were deetected, with most fusions disrupting RB1, TP53, and ATRX/DAXX, and one fusion (ACTG2-ALK) being potentially targetable. WGS results demonstrated that 76% (16 of 21) of the samples harbored chromoplexy and/or chromothripsis. Clinically actionable mutational signatures of homologous-recombination DNA-repair deficiency (HRD) and microsatellite instability (MSI) were identified in 25% (12 of 48) and 2% (1 of 48) of fresh frozen uLMS, respectively. Finally, we found olaparib (PARPi; P = 0.002), GS-626510 (C-MYC/BETi; P < 0.000001 and P = 0.0005), and copanlisib (PIK3CAi; P = 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.

Intrapartum pyrexia, cardiotocography traces and histologic chorioamnionitis: a case-control study.

OBJECTIVES: To compare characteristics of labor, cardiotocography traces, and maternal and neonatal outcomes, in a cohort of pregnancies at term complicated by maternal intrapartum pyrexia, with or without a histologic diagnosis of chorioamnionitis. METHODS: This is a retrospective case-control study including pregnancies at term with detection of maternal intrapartum pyrexia, delivered between January 2020 and June 2021. Cardiotocography traces were entirely evaluated, since admission till delivery, and classified according to the International Federation of Obstetrics and Gynecology (FIGO) guideline. Maternal and neonatal outcomes were also recorded as secondary outcomes. Placentas have been studied according to the Amniotic Fluid Infection Nosology Committee. RESULTS: Forty four patients met the inclusion criteria and were included in the study cohort. There was a significant association between the use of oxytocin augmentation in labor and the histologic diagnosis of chorioamnionitis. A significative recurrence of loss and/or absence of accelerations at the point of pyrexia was also documented in women with histological chorioamnionitis compared to the others. CONCLUSIONS: Chorioamnionitis appears to be associated with myometrial disfunction, as suggested by the increased use of oxytocin augmentation during active labor of women at term with intrapartum pyrexia and histologic diagnosis of chorioamnionitis.

Health-Related Quality of Life after Hysterectomy for Endometrial Cancer: The Impact of Enhanced Recovery after Surgery Shifting Paradigm.

OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols provide well-known benefits in the immediate recovery with a shorter length of stay (LOS) and also in gynecological surgery. However, the impact of ERAS has not been clearly showed yet regarding long-term consequences and health-related quality of life (HRQL). The aim of this study was to investigate the impact of ERAS on HRQL after hysterectomy for endometrial cancer. DESIGN: An observational retrospective study with propensity score matching (PSM) was performed. PARTICIPANTS: We administered the SF-36 validated questionnaire to women underwent hysterectomy and lymph nodal staging before and after introducing ERAS protocol, getting, respectively, a standard practice (SP) and ERAS group. SETTINGS: The study was conducted at the academic hospital. METHODS: We collected demographic, clinical, surgical and postoperative data and performed a PSM of the baseline confounders. We administered the questionnaire 4 weeks after the surgery. The SF-36 measures HRQL using eight scales: physical functioning (PF), role physical (RLP), bodily pain (BP), general health (GH), vitality (Vt), social functioning (SF), role emotional (RLE) and mental health (MH). RESULTS: After PSM, we enrolled a total of 154 patients, 77 in each group (SP and ERA). The two groups were similar in terms of age, BMI, anesthetic risk, Charlson comorbidity index (CCI), and surgical technique (minimally invasive vs. open access). Median LOS was shorter for ERAS group (5 vs. 3 days; p = 0.02), while no significant differences were registered in the rates of postoperative complications (16.9% vs. 17.4%; p = 0.66). Response rates to SF-36 questionnaire were 89% and 92%, respectively, in SP and ERAS group. At multivariate analyzes, the mean scores of SF-36 questionnaire, registered at 28 days weeks after surgery (range 26-32 days), were significantly higher in ERAS group for PF (73.3 vs. 91.6; p < 0.00), RLP (median 58.3 vs. 81.2; p = 0.02), and SF (37.5 vs. 58.3; p = 0.01) domains, when compared to SP patients. LIMITATIONS: Further follow-up was not possible due to the anonymized data derived from clinical audit. CONCLUSIONS: ERAS significantly increases the HRQL of women who underwent surgery for endometrial cancer. HRQL assessment should be routinely implemented in the ERAS protocol.

Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion.

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

A strange case of pleuritic pain in the third trimester of pregnancy.

Pulmonary sequestration is an uncommon congenital malformation of the lung, generally diagnosed in childhood or adolescence, corresponding to dysplastic lung tissue not communicating with the rest of vascular or bronchial lung system but receiving an arterial blood supply from systemic arteries. Currently, surgical resection is usually indicated in order to prevent or treat related symptoms or complications, although controversy exists regarding its use in asymptomatic patients and adults. We present the case of a 32-year-old pregnant woman with acute chest pain and vomiting diagnosed with intralobar sequestration at 32+2 weeks of gestation and treated with pulmonary lobectomy after giving birth by cesarean section at 33+0 weeks of gestation.

L1CAM expression as a predictor of platinum response in high-risk endometrial carcinoma.

For high-risk endometrial cancer (EC) patients, adjuvant chemotherapy is recommended to improve outcome. Yet, predictive biomarkers for response to platinum-based chemotherapy (Pt-aCT) are currently lacking. We tested expression of L1 cell-adhesion molecule (L1CAM), a well-recognised marker of poor prognosis in EC, in tumour samples from high-risk EC patients, to explore its role as a predictive marker of Pt-aCT response. L1CAM expression was determined using RT-qPCR and immunohistochemistry in a cohort of high-risk EC patients treated with Pt-aCT and validated in a multicentric independent cohort. The association between L1CAM and clinicopathologic features and L1CAM additive value in predicting platinum response were determined. The effect of L1CAM gene silencing on response to carboplatin was functionally tested on primary L1CAM-expressing cells. Increased L1CAM expression at both genetic and protein level correlated with high-grade, non-endometrioid histology and poor response to platinum treatment. A predictive model adding L1CAM to prognostic clinical variables significantly improved platinum response prediction (C-index 78.1%, P = .012). In multivariate survival analysis, L1CAM expression was significantly associated with poor outcome (HR: 2.03, P = .019), potentially through an indirect effect, mediated by its influence on response to chemotherapy. In vitro, inhibition of L1CAM significantly increased cell sensitivity to carboplatin, supporting a mechanistic link between L1CAM expression and response to platinum in EC cells. In conclusion, we have demonstrated the role of L1CAM in the prediction of response to Pt-aCT in two independent cohorts of high-risk EC patients. L1CAM is a promising candidate biomarker to optimise decision making in high-risk patients who are eligible for Pt-aCT.

Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors.

Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBOC) to evaluate the evolutionary history. Lastly, to search for therapeutic targets, we evaluated the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 on primary tumors and xenografts harboring c-MYC amplifications. In line with previous studies, the large majority of germline and somatic mutations were found in BRCA1/2 (21%) and TP53 (86%) genes, respectively. Among mutations in known cancer driver genes, 77% were transmitted from primary tumors to metastatic tumors, and 80% from primary to recurrent tumors, indicating that driver mutations are commonly retained during ovarian cancer evolution. Importantly, the number, mutation spectra, and signatures in matched primary-metastatic tumors were extremely similar, suggesting transcoelomic metastases as an early dissemination process using preexisting metastatic ability rather than an evolution model. Similarly, comparison of SBOC showed extensive sharing of somatic mutations, unequivocally indicating a common ancestry in all cases. Among the 17 patients with matched tumors, four patients gained PIK3CA amplifications and two patients gained c-MYC amplifications in the recurrent tumors, with no loss of amplification or gain of deletions. Primary cell lines and xenografts derived from chemotherapy-resistant tumors demonstrated sensitivity to JQ1 and GS-626510 (P = 0.01), suggesting that oral BET inhibitors represent a class of personalized therapeutics in patients harboring recurrent/chemotherapy-resistant disease.

Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy.

The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs). Somatic copy number variants (CNVs) identified 12 copy number gains and 40 losses, occurring more often than expected by chance, with the most frequent events in pathways similar to those found from analysis of single nucleotide variants (SNVs), including the ERBB2/PI3K/AKT/mTOR, apoptosis, chromatin remodeling, and cell cycle. To validate specific SNVs as targets, we took advantage of primary cervical tumor cell lines and xenografts to preclinically evaluate the activity of pan-HER (afatinib and neratinib) and PIK3CA (copanlisib) inhibitors, alone and in combination, against tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway (71%). Tumors harboring ERBB2 (5.8%) domain mutations were significantly more sensitive to single agents afatinib or neratinib when compared to wild-type tumors in preclinical in vitro and in vivo models (P = 0.001). In contrast, pan-HER and PIK3CA inhibitors demonstrated limited in vitro activity and were only transiently effective in controlling in vivo growth of PIK3CA-mutated cervical cancer xenografts. Importantly, combinations of copanlisib and neratinib were highly synergistic, inducing long-lasting regression of tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway. These findings define the genetic landscape of cervical cancer, suggesting that a large subset of cervical tumors might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs.

Ultrasound and magnetic resonance imaging in the diagnosis of clinically significant placenta accreta spectrum disorders.

OBJECTIVES: We aimed to assess the performance of ultrasound (US) and magnetic resonance imaging (MRI) signs for antenatal detection of placenta accreta spectrum (PAS) disorders in women with placenta previa (placental edge ≤2 cm from the internal uterine orifice, ≥260/7 weeks' gestation) with and without a history of previous Caesarean section. METHODS: Single center prospective observational study. US suspicion of PAS was raised in the presence of obliteration of the hypoechoic space between uterus and placenta, interruption of the hyperechoic uterine-bladder interface and/or turbulent placental lacunae on color Doppler. All MRI studies were blindly evaluated by a single operator. PAS was defined as clinically significant when histopathological diagnosis was associated with at least one of: intrauterine balloon placement, compressive uterine sutures, peripartum hysterectomy, uterine or hypogastric artery ligature, uterine artery embolization. RESULTS: A total of 39 women were included: 7/39 had clinically significant PAS. There were 6/18 cases of PAS with anterior placenta: hypoechoic space interruption and placental lacunae were the most sensitive sonographic signs (83%), while abnormal hyperechoic interface was the most specific (83%). On MRI, focal myometrial interruption and T2 intraplacental dark bands showed the best sensitivity (83%), bladder tenting had the best specificity (100%). 1/21 women with posterior placenta had PAS. There was substantial agreement between US and MRI in patients with anterior placenta (κ=0.78). CONCLUSIONS: US and MRI agreement in antenatal diagnosis of clinically significant PAS was maximal in high-risk women. Placental lacunae on ultrasound scan and T2 intraplacental hypointense bands on MRI should trigger the suspicion of PAS.

Uterine torsion and intrauterine growth restriction: Case report and systematic literature review.

PURPOSE: Uterine torsion (UT) in pregnancy is a rare condition in obstetric practice. It is defined as a rotation of the uterus of more than 45° around its long axis. Presentations are varied and, most of the time, this condition is recognized at laparotomy or cesarean section (CS). The aim of this study is to summarize the latest evidence about UT in pregnancy. METHODS: A systematic research of the literature was conducted fetching all papers published from March 2006 to June 2020. We collected data regarding clinical features, treatment, and feto-maternal outcomes. Finally, we reported data of a case of UT associated with intrauterine growth restriction (IUGR) diagnosed and treated at our institution. RESULTS: According to our search strategy, 38 articles were included. In 66% of the cases, acute symptomatology was present at the onset, most frequently abdominal pain was reported. In one-third of the cases, UT was diagnosed during CS without clinical suspicion. Only in two cases, including our case, IUGR was reported. Most (66%) of the cases presented a 180° torsion. In the majority of the cases, a CS was performed also with a deliberate or accidental posterior hysterotomy. One and six cases of maternal and fetal death were, respectively, reported. CONCLUSION: UT is an infrequent obstetric condition but should be considered in case of abdominal pain, vomiting, or shock presentation during pregnancy. It could lead to a reduction in uterine blood flow contributing to poor placental perfusion, even though more evidence is needed to clarify this link.

Clear cell degeneration associated with endometriosis of abdominal wall after cesarean section: A case report and systematic review of literature.

AIM: The scar of cesarean section (CS) is the most common site of abdominal wall endometriosis (AWE), whose tumor degeneration has been reported in an increasing number of cases; the most frequent histological type is clear cell carcinoma (CCC). METHODS: We conducted a systematic research of the literature, collecting data regarding the evidence on tumor degeneration from AWE after CS. Moreover, we reported a case of clear cell borderline tumor (CCBT) originating from AWE. RESULTS: We included data of 37 patients with diagnosis of CCC. The average time between the last CS and the diagnosis of CCC was around 15 years. Overall, 26.0% and 73.9% patients received exclusive local abdominal resection of the lesion and additional surgery, respectively. Lymph nodes involvement was detected in 26.0 % patients and adjuvant chemotherapy was administered in 52.0 % cases. During follow-up period, 15.2% patients died of disease, 32.6% had no evidence of disease, and 17.4% recurred. We diagnosed a CCBT arose in a patients with AWE and a personal history of several surgical procedures for endometriosis, a CS and a subsequent transverse laparotomy. We performed an open bilateral ovariectomy and a large excision of the endometriotic abdominal lesion. CONCLUSION: Tumor degeneration from AWE seems to be a real occurrence with an increasing number of events. Considering the lack of risk factors and diagnostic instruments for tumor degeneration, the removal of AWE localization could be advisable, even though there was long average time between the trigger surgery and the tumor finding.

Current Treatment Options for Cervical Leiomyomas: A Systematic Review of Literature.

Background and objectives: Cervical leiomyomas are a rare benign disease. Although they are mainly treated surgically, currently, there is not a standardized treatment for cervical leiomyomas. This study aims to summarize current literature evidence about treatment options for cervical leiomyomas. Materials and methods: A systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library, including observational prospective and retrospective studies, case series and case reports. We collected data regarding studies related to treatment options for cervical leiomyomas, evaluating the following aspects: study design, population, treatment type, rate of surgical complications, and fertility outcome. Results: According to literature research, 38 articles were included. Among 214 patients, the weighted average age was 39.4 years-old; 23 patients were pregnant. Most of the leiomyomas (78%) were extracervical; in 22% of cases (29 patients) were intracervical; 188 patients (88%) received surgical treatment, 6 (3%) received exclusive conservative management and 21 (10%) underwent interventional radiology treatment. One hundred twenty-seven patients (67.5%) underwent myomectomy, while 54 (28.7%) and 7 (3.7%) hysterectomy and trachelectomy, respectively. Cervical myomectomy was performed by open surgery in 21 out of 127 cases (16.5%), while in 92 (72.4%) and 6 (4.7%) patients the surgical approach was performed by traditional and robot-assisted laparoscopy, respectively. The total rate of surgical complications was 5.6%. Conclusion: Surgery is the primary therapeutic option for cervical leiomyomas with a low rate of surgical complications. Interventional radiology techniques have reported promising but still limited results.

Expression profiles of PRKG1, SDF2L1 and PPP1R12A are predictive and prognostic factors for therapy response and survival in high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGS-EOCs) is generally sensitive to front-line platinum (Pt)-based chemotherapy although most patients at an advanced stage relapse with progressive resistant disease. Clinical or molecular data to identify primary resistant cases at diagnosis are not yet available. HGS-EOC biopsies from 105 Pt-sensitive (Pt-s) and 89 Pt-resistant (Pt-r) patients were retrospectively selected from two independent tumor tissue collections. Pathway analysis was done integrating miRNA and mRNA expression profiles. Signatures were further validated in silico on a cohort of 838 HGS-EOC cases from a published dataset. In all, 131 mRNAs and 5 miRNAs belonging to different functionally related molecular pathways distinguish Pt-s from Pt-r cases. Then, 17 out of 23 selected elements were validated by orthogonal approaches (SI signature). As resistance to Pt is associated with a short progression-free survival (PFS) and overall survival (OS), the prognostic role of the SI signature was assessed, and 14 genes associated with PFS and OS, in multivariate analyses (SII signature). The prognostic value of the SII signature was validated in a third extensive cohort. The expression profiles of SDF2L1, PPP1R12A and PRKG1 genes (SIII signature) served as independent prognostic biomarkers of Pt-response and survival. The study identified a prognostic molecular signature based on the combined expression profile of three genes which had never been associated with the clinical outcome of HGS-EOC. This may lead to early identification, at the time of diagnosis, of patients who would not greatly benefit from standard chemotherapy and are thus eligible for novel investigational approaches.

Validation of an enhanced recovery after surgery protocol in gynecologic surgery: an Italian randomized study.

BACKGROUND: The enhanced recovery after surgery concept, which was introduced 20 years ago, is based on a multimodal approach to improve the functional rehabilitation of patients after surgery. OBJECTIVE: This study aimed to validate an enhanced recovery after surgery protocol in gynecologic surgery for both benign and malignant diseases (endometrial cancer and advanced ovarian cancer) and to measure the adherence to the enhanced recovery after surgery protocol items in a randomized trial setting. STUDY DESIGN: In this trial (NCT03347409), we randomly assigned patients to undergo standard perioperative care or enhanced recovery after surgery protocol. The primary outcome is a shorter length of stay in favor of the enhanced recovery after surgery protocol. Secondary outcomes include measurement of adherence to the enhanced recovery after surgery protocol items: comparison of postoperative pain, vomiting, and nausea; anesthesiologic and surgical complications up to 30 days after surgery; rate of readmissions; the time to event in hours for bowel movements, flatus, drinking, hunger, eating, and walking; and the quality of recovery using a validated questionnaire (QoR-15). Finally, we explored the length of stay in the prespecified subgroups at randomization, based on the type of surgical access and gynecologic disease. RESULTS: A total of 168 women were available for analysis: 85 women (50.6%) were assigned to the standard perioperative care group, and 83 women (49.4%) were assigned to the enhanced recovery after surgery protocol group. The 2 groups were similar for age, body mass index, comorbidities, anesthesiological risk, smoking habits, surgical access, and complexity of surgical procedures. Seventy-two patients (42.9%) underwent surgery for benign disease, 48 (28.6%) for endometrial cancer, and 48 (28.6%) for ovarian cancer. Women in the enhanced recovery after surgery protocol group had a shorter length of stay (median: 2 [interquartile range, 2-3] vs 4 [interquartile range, 4-7] days; P<.001). A decreased rate of postoperative complications was noted for the enhanced recovery after surgery protocol group, as well as an earlier time to occur for all the events. Mean adherence to protocol items was 84.8% (95% confidence interval, 79.7-89.8), and we registered a better satisfaction in the enhanced recovery after surgery protocol group. The shortening of the length of stay was confirmed also in the prespecified subgroup analysis. CONCLUSION: Application of the enhanced recovery after surgery protocol in gynecologic surgery translated to a shorter length of stay regardless of surgical access and type of gynecologic disease. Adherence to the enhanced recovery after surgery protocol items in the setting of a randomized trial was high.

Laparoscopic Access with Optical Gasless Trocar: A Single-center Experience of 7431 Procedures.

STUDY OBJECTIVE: To analyze the complications experienced and describe laparoscopic surgery using a gasless optical trocar. DESIGN: A retrospective study. SETTING: A department of obstetrics and gynecology in a tertiary center in Italy. PATIENTS: Seven thousand four hundred thirty-one surgical procedures were performed. INTERVENTIONS: From the hospital database, data were evaluated regarding major complications of laparoscopy with the ENDOPATH XCEL Bladeless Trocar (Ethicon, Johnson & Johnson, Somerville, NJ) performed between 2000 and 2017 by different laparoscopic surgeons. MEASUREMENTS AND MAIN RESULTS: The mean age of the patients was 40.66 ± 12.06 years (range, 13-91 years). The mean body mass index was 22.12 ± 3.64 kg/m2 (range, 15.74-41.51 kg/m2). The overall complication rate was 0.31% (23/7431 cases). Major complications included stomach perforation in 1 procedure (0.014%), ileal perforation in 2 procedures (0.028%), and blood vessel perforation in 1 procedure (0.014%). Twelve procedures were completed with initial access through the omentum and 2 through an ovarian cyst. In 5 procedures (0.067%), conversion to laparotomy was required because the optical trocar failed to reach the abdominal cavity. With regard to complications requiring further intervention (n = 9), the rate of complications was 0.12%. CONCLUSIONS: The optical gasless trocar is a feasible laparoscopic entry technique. The complication rate is lower than those reported previously.

FXYD5 (Dysadherin) upregulation predicts shorter survival and reveals platinum resistance in high-grade serous ovarian cancer patients.

BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is generally associated with a very dismal prognosis. Nevertheless, patients with similar clinicopathological characteristics can have markedly different clinical outcomes. Our aim was the identification of novel molecular determinants influencing survival. METHODS: Gene expression profiles of extreme HGSOC survivors (training set) were obtained by microarray. Differentially expressed genes (DEGs) and enriched signalling pathways were determined. A prognostic signature was generated and validated on curatedOvarianData database through a meta-analysis approach. The best prognostic biomarker from the signature was confirmed by RT-qPCR and by immunohistochemistry on an independent validation set. Cox regression model was chosen for survival analysis. RESULTS: Eighty DEGs and the extracellular matrix-receptor (ECM-receptor) interaction pathway were associated to extreme survival. A 10-gene prognostic signature able to correctly classify patients with 98% of accuracy was identified. By an 'in-silico' meta-analysis, overexpression of FXYD domain-containing ion transport regulator 5 (FXYD5), also known as dysadherin, was confirmed in HGSOC short-term survivors compared to long-term ones. Its prognostic and predictive power was then successfully validated, both at mRNA and protein level, first on training than on validation sample set. CONCLUSION: We demonstrated the possible involvement of FXYD5 and ECM-receptor interaction signal pathway in HCSOC survival and prognosis.

Laparoscopic management of a large urethral leiomyoma.

INTRODUCTION AND HYPOTHESIS: A 42-year-old female presented with a 12-cm mass bulging the anterior vaginal wall and causing urgency urinary incontinence and bulk symptoms. METHODS: Imaging showed a tumor originating from the dorsal and cranial part of the urethra and developing in the vesicouterine space and vesicovaginal septum, dislocating the bladder ventrally and the uterus cranial-dorsally. RESULTS: Tranvaginal biopsy showed a benign leiomyoma. A laparoscopic approach with development of the vesicouterine space permitted a safe partial morcellation of the myoma. After the bladder and vaginal wall had been completely freed, further caudal dissection was conducted with isolation of the distal cranio-dorsal portion of the urethra. The dissection plane with the vaginal wall was developed up to the caudal margin of the urethral myoma almost corresponding to the vulvar plane, and total excision of the lesion was performed. CONCLUSION: Laparoscopic management of urethral leiomyomas that develop into the vesicouterine space and vesicovaginal septum is feasible and safe also for very large lesions.