Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVES: Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of patients with ovarian cancer, a recent systematic review and meta-analysis is lacking. The objective of this study was to determine the association of ctDNA with progression-free-survival and overall survival in patients with epithelial ovarian cancer. METHODS: An electronic search was conducted using PubMed (MEDLINE), Embase, CENTRAL (Cochrane Library), and CINAHL-Complete from January 2000 to September 15, 2023. To be included in the analysis the studies had to meet the following pre-specified inclusion criteria: (1) evaluable ctDNA; (2) progression-free-survival and overall survival reported as hazard ratio (HR); and (3) the patient population had epithelial ovarian cancer at the time of ctDNA detection. We evaluated the association of ctDNA with progression-free survival and overall survival. Secondary outcomes focused on sub-group analysis of genomic alterations and international Federation of Gynecology and Obstetrics (FIGO) stage. RESULTS: A total of 26 studies reporting on 1696 patients with epithelial ovarian cancer were included. The overall concordance rate between plasma-based and tissue-based analyses was approximately 62%. We found that a high level of ctDNA in epithelial ovarian cancer was associated with worse progression-free survival (HR 5.31, 95% CI 2.14 to 13.17, p<0.001) and overall survival (HR 2.98, 95% CI 1.86 to 4.76, p<0.0001). The sub-group analysis showed a greater than threefold increase in the risk of relapse in patients with positive HOXA9 meth-ctDNA (HR 3.84, 95% CI 1.57 to 9.41, p=0.003). CONCLUSIONS: ctDNA was significantly associated with worse progression-free survival and overall survival in patients with epithelial ovarian cancer. Further prospective studies are needed. PROSPERO REGISTRATION NUMBER: CRD42023469390.

Innovative Ultrasound Criteria for the Diagnosis of Adenomyosis and Correlation with Symptoms: A Retrospective Re-Evaluation.

The 2022 Delphi revision of the MUSA (Morphological Uterus Sonographic Assessment) criteria for the ultrasound diagnosis of adenomyosis divides the ultrasound signs for diagnosis into direct and indirect ones, considering the presence of at least one direct sign as a mandatory criterion. This study aimed to reclassify the patients referred to the Pelvic Pain specialist outpatient clinic of the Gynecological Clinic of Udine according to the new criteria, evaluating the number of overdiagnoses and the possible correlation between the direct and indirect signs and the patients' symptoms. 62 patients affected by adenomyosis were retrospectively recruited. The patients were then re-evaluated by ultrasound and clinically. At least one direct sign of adenomyosis was found in 52 patients, while 16% of the population examined did not present any. There was no statistically significant difference between patients presenting direct signs and those presenting none for the symptoms considered. According to the new criteria, 16% of the patients examined were not affected by adenomyosis; applying the new consensus to symptomatic patients could increase false negatives. In a population of symptomatic patients, the diagnosis of adenomyosis is still highly probable even without direct ultrasound signs, given the clinical symptoms and having ruled out other causes of such symptoms.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review.

BACKGROUND: PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. METHODS: We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. RESULTS: This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). CONCLUSION: This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.

Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study.

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36-42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.

A survey on the current practice of indicating an elective cesarean after a previous myomectomy.

OBJECTIVE: The objective of this study was to evaluate the attitude of obstetricians/gynecologists toward indicating an elective cesarean delivery in pregnant patients with a previous myomectomy. MATERIALS AND METHODS: Web-based multiple-choice questions survey evaluating the attitude to indicate a cesarean with a composite summated score (range 56-280) from a 56-item Likert scale: score 56-112: weak attitude, 113-168: moderate, 169-224: strong, and 225-280: very strong. The reliability of the score (internal consistency) was evaluated with Cronbach's alpha coefficient. The association between the score and participants' characteristics was determined with a bivariate analysis followed by linear regression analysis. The "global importance" of each risk factor was defined as the prevalence of the answers: "moderately important", "very important", and "extremely important" on the Likert scale. Factors with a "global importance" >75% were considered "crucial" in influencing the choice to indicate a cesarean. RESULTS: One-hundred-twenty obstetricians/gynecologists responded (response rate 70.6%). The mean ± SD composite summated score was 137 ± 31; 30 (25.0%) participants presented a "weak attitude to cesarean", 68 (56.7%) a "moderate attitude", 22 (18.3%) a "strong attitude", and none a "very strong attitude". The Cronbach's alpha was 0.934 (high internal consistency). A self-reported number of myomectomies performed per year >50 was associated with a lower score (-25 points, 95% CI -50 to -1, p = 0.04). Eight criteria resulted "crucial" in indicating a cesarean: opening of the endometrial cavity, monopolar electrosurgery, time surgery-pregnancy <6 months, 2+ previous myomectomies, hematoma formation in the surgical wound, 3+ removed fibroids, and a FIGO4 or FIGO3 removed fibroid. CONCLUSIONS: Obstetricians/gynecologists are cautious to indicate a cesarean in pregnant patients with a previous myomectomy, except for cases at hypothetic high-risk for uterine rupture, mainly supported by weak evidence. Information to patients and among clinicians is crucial to avoid inappropriate cesarean indications.KEY MESSAGESObstetricians/gynecologists are cautious to indicate a cesarean in pregnant patients with a previous myomectomy.Information to patients and among clinicians is crucial to avoid inappropriate cesarean indications in pregnant patients with a previous myomectomy.

Effect of expiratory flow limitation on ventilation/perfusion mismatch and perioperative lung function during pneumoperitoneum and Trendelenburg position.

BACKGROUND: Laparoscopic surgery and Trendelenburg position may affect the respiratory function and alter the gas exchange. Further the reduction of the lung volumes may contribute to the development of expiratory flow limitation (EFL). The latter is associated with an increased risk of postoperative pulmonary complications. Our aim was to investigate the incidence of EFL and to evaluate its effect on pulmonary function and intraoperative V/Q mismatch. METHODS: This is a prospective study on patients undergoing elective laparoscopic gynecological surgery. We evaluated respiratory mechanics, V/Q mismatch and presence of EFL after anesthesia induction, during pneumoperitoneum and Trendelenburg position and at the end of surgery. Intraoperative gas exchange and hemodynamic were also recorded. Clinical data were collected until seven days after surgery to evaluate the onset of pulmonary postoperative complications (PPCs). RESULTS: Among the 66 patients enrolled, 25/66 (38%) exhibited EFL during surgery, of whom 10/66 (15%) after anesthesia induction, and the remaining 15 patients after pneumoperitoneum and Trendelenburg position. Median PEEP able to reverse flow limitation was 7 [7-10] cmH2O after anesthesia induction and 9 [8-15] cmH2O after pneumoperitoneum and Trendelenburg position. Patients with EFL had significantly higher shunt (17 [2-25] vs. 9 [1-19]; P=0.05), low V̇/Q̇ (27 [20-70] vs. 15 [10-22]; P=0.05) and high V̇/Q̇ (10 [7-14] vs. 6 [4-7]; P=0.024). At the end of surgery, only high V/Q was significantly higher in EFL patients. Further, they exhibited higher incidence of postoperative pulmonary complication (48% (12/25) vs. 15% (6/41), P=0.005), hypoxemia and hypercapnia (80% [20/25] vs. 32% [13/41]; P<0.001). CONCLUSIONS: Expiratory flow limitation is a common phenomenon during gynecological laparoscopic surgery associated with worsen gas exchange, increased V/Q mismatch and altered lung mechanics. Our study showed that patients experiencing EFL during surgery showed a higher risk for PPCs.

Management of Patients Diagnosed with Endometrial Cancer: Comparison of Guidelines.

Endometrial cancer is the most common gynecological malignancy in Europe and its management involves a variety of health professionals. In recent years, big discoveries were made concerning the management of patients diagnosed with endometrial cancer, particularly in the field of molecular biology and minimally invasive surgery. This requires the continuous updating of guidelines and protocols over the years. In this paper, we aim to summarize and compare common points and disparities among protocols for management of patients diagnosed with endometrial cancer by leading international gynecological oncological societies. We therefore systematically report the parallel among the guidelines based on the various steps patients with endometrial cancer usually undergo. The comparison between American and European protocols revealed some relevant disparities, in particular regarding surgical staging, molecular biology application as a prognostic tool and follow up regimens. This could possibly cause differences in interpreting and applying protocols in clinical practice in small centers, leading to a lack of adherence to guidelines or even prompting a confusing mix of them.

Corrigendum: Serum IgG antibodies from pregnant women reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein.

[This corrects the article DOI: 10.3389/fimmu.2017.00411.].

Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

BACKGROUND: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. METHODS: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). RESULTS: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. CONCLUSIONS: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Preservation of the inferior mesenteric artery in laparoscopic nerve-sparing colorectal surgery for endometriosis.

Laparoscopic rectosigmoid resection for endometriosis is usually performed with the section of the inferior mesenteric artery (IMA) distal to the left colic artery (low-tie ligation). This study was to determine outcomes in IMA-sparing surgery in endometriosis cases. A single-center retrospective study based on the analysis of clinical notes of women who underwent laparoscopic rectosigmoid segmental resection and IMA-sparing surgery for deep infiltrating endometriosis with bowel involvement between March the 1st, 2018 and February the 29th, 2020 in a referral hospital. During the study period, 1497 patients had major gynecological surgery in our referral center, of whom 253 (17%) for endometriosis. Of the 100 patients (39%) who had bowel endometriosis, 56 underwent laparoscopic nerve-sparing rectosigmoid segmental resection and IMA-sparing surgery was performed in 53 cases (95%). Short-term complications occurred in 4 cases (7%) without any case of anastomotic leak. Preservation of the IMA in colorectal surgery for endometriosis is feasible, safe and enables a tension-free anastomosis without an increase of postoperative complication rates.

Fetal disseminated intravascular coagulopathy, hydrops and massive umbilical vein thrombosis consequence of a rare placental condition: multifocal chorangiomatosis.

Purpose: Villous capillary lesions are rare abnormal placental developmental conditions which include chorangiosis, chorangiomatosis, chorangioma and a rare variant of the latter called multiple chorangioma syndrome. The causes of villous capillary lesion are not completely clear but appear to involve excessive angiogenesis. MATERIALS AND METHODS: In this paper we start illustrating our experience of multifocal chorangiomatosis with the newborn affected by massive umbilical vein thrombosis, disseminated intravascular coagulopathy and hydrops, going to a literature review of cases available.Results: Two other similar cases have been previously published in literature. Comparing clinical characteristics and fetal outcomes, we confirm the association with unfavorable neonatal outcome mentioned in literature. Our case is the first characterized by severe hemolytic anemia, thrombocytopenia, heart congestion with the overlap of disseminated intravascular coagulopathy and massive umbilical vein thrombosis and congenital anomalies. CONCLUSIONS: Our clinical case and the review of literature highlight how multifocal chorangiomatosis, within the three subgroups identified, is the rarer form with distinct placental features and the worst outcomes for neonates. No cases of multifocal chorangiomatosis have never been described prenatally and, for further studies, could be reasonable investigate the involvement of some growth factors like vascular endothelial growth factor and placental growth factor that could lead to a detection of a subgroup of patient at higher risk to manifest placental vascular lesions and the follow fetal and maternal complications.

Impact of COVID-19 on surgical activities and personnel: lessons for the future.

BACKGROUND: COVID-19 pandemic has impacted professional, economic and social activities. In the surgical field, it has brought changes to operating activities, the organization of workforces, the protection measures for patients and personnel against possible intraoperative transmissions as well as training young surgeons. This study intends to assess the extent of this impact in our institution. METHODS: The patients operated on in nine Operating Units (OUs) in the period February 1 - March 31, 2020, with follow-ups on April 30, 2020, were evaluated both retrospectively and prospectively. Organizational, clinical and impact parameters on staff were evaluated. RESULTS: Of the 833 consecutive admitted patients, 742 were operated on, 705 of whom were recruited for the study. Compared to the same period in 2019 there was a decrease in the number of operations (742 compared to 1187), similar use of intensive care unit (ICU), a diagnostic activity only for symptomatic patients, heterogeneity in organizational behaviors, an impact on staff who highlighted concerns about getting sick or passing the infection on to others (87.64%) or their family members (75.14%). CONCLUSIONS: The present study made it possible to detect the need to make significant changes in the clinical, organizational and teaching fields, for which some operational proposals are suggested.

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. METHODS: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. RESULTS: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). CONCLUSION: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.

MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining.

PURPOSE: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138. METHODS: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC. RESULTS: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138. CONCLUSION: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

Association between Endometrial Polyps and Chronic Endometritis: Is It Time for a Paradigm Shift in the Pathophysiology of Endometrial Polyps in Pre-Menopausal Women? Results of a Systematic Review and Meta-Analysis.

BACKGROUND: Chronic endometritis (CE) and endometrial polyps (EPs) are common conditions in reproductive age women. CE is an infectious disorder of the endometrium characterized by signs of chronic inflammation at hysteroscopic and histological analyses. EPs are abnormal endometrial growths containing glands, stroma and blood vessels projecting from the lining of the uterus. During the last years, different authors have investigated the correlation between CE and EPs, with controversial results. The aim of this study was to summarize available evidence on the potential correlation between CE and EPs. DESIGN: Systematic literature review and meta-analysis. METHODS: Observational-studies were identified by searching electronic databases from their inception to September 2021. Only studies on pre-menopausal women were included. Statistical analysis was performed using MedCalc 16.4.3 (Ostend, Belgium) and Review Manager version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). The summary measures were reported as pooled proportion or odds ratio (OR) with 95% confidence interval (CI). The primary outcome was to evaluate the prevalence of CE in women with EPs. The secondary outcome was to determine the prevalence of CD-138-positive EPs among EPs. Tertiary outcomes were to compare the prevalence of CE in women with EPs versus women with a non-polypoid endometrium and to compare the prevalence of CE in women with a single EP versus women with multiple EPs. RESULTS: Eight observational studies (n = 3225 patients) were included in quantitative synthesis. Pooled prevalence of CE among women with EPs was 51.35% (95% CI, 27.24-75.13%). Pooled proportion of CD-138-positive EPs among EPs was 70.73% (95% CI, 55.73-83.68%). Women with EPs showed higher prevalence of CE compared to women without EPs (OR 3.07, 95% CI 1.59-5.95). Women with ≥3 EPs had higher prevalence of CE then women with a single EP (OR 3.43, 95% CI 1.83-6.46). CONCLUSIONS: In pre-menopausal women, CE and EPs may have a dependent relationship and may represent two consequent steps of a common pathological process.

The impact of orthotopic reconstruction on female sexuality and quality of life after radical cystectomy for non-malignant bladder conditions.

OBJECTIVE: To review the literature on the impact on female quality of life and sexual function of orthotopic reconstruction after radical cystectomy for non-malignant bladder conditions. Radical cystectomy is commonly required to treat malignant conditions but may also be considered for the treatment of non-malignant diseases. These heterogeneous group of disorders includes interstitial cystitis, painful bladder syndrome, neurogenic bladder, haemorrhagic/ radiation cystitis, endometriosis and refractory genitourinary fistula. Treatment begins with non-invasive medical therapies but, in non-responder cases, a surgical solution should be considered. Such invasive techniques include urinary diversion and reconstructive procedures that have an impact on healthrelated quality of life, physical, social, and mental status. MATERIALS AND METHODS: This narrative review research was done using the PubMed database up until 2020, July. All papers referring to cystectomy for benign indication were considered. RESULTS: In comparison to other reconstructive options, orthotopic neobladder allows the restoration of a normal self-image and consequently it is the most suitable procedure when a surgical reconstruction is necessary for non-malignant conditions. However, women can face many disorders that impact on everyday life, such as voiding dysfunction or sexual activity problems. CONCLUSIONS: Scant data is available about quality of life, sexual life and self-perception in women treated by cystectomy for benign conditions and most literature is dedicated to those indicators in cancer patients. More research is needed to understand the tolerability and the quality of life results of the female population affected by benign conditions undergoing this kind of surgical approach.

Targeting the NLRP3 Inflammasome as a New Therapeutic Option for Overcoming Cancer.

Inflammasomes are multiprotein complexes that regulate the maturation and secretion of the proinflammatory cytokines interleukin-1beta (IL-1ß and interleukin-18 (IL-18) in response to various intracellular stimuli. As a member of the inflammasomes family, NLRP3 is the most studied and best characterized inflammasome and has been shown to be involved in several pathologies. Recent findings have made it increasingly apparent that the NLRP3 inflammasome may also play a central role in tumorigenesis, and it has attracted attention as a potential anticancer therapy target. In this review, we discuss the role of NLRP3 in the development and progression of cancer, offering a detailed summary of NLRP3 inflammasome activation (and inhibition) in the pathogenesis of various forms of cancer. Moreover, we focus on the therapeutic potential of targeting NLRP3 for cancer therapy, emphasizing how understanding NLRP3 inflammasome-dependent cancer mechanisms might guide the development of new drugs that target the inflammatory response of tumor-associated cells.

Diagnostic accuracy of prenatal ultrasound in identifying the level of the lesion in fetuses with open spina bifida: A systematic review and meta-analysis.

INTRODUCTION: The role of prenatal ultrasound in correctly identifying the level of the lesion in fetuses with open spina bifida has yet to be determined. The primary aim of this systematic review was to report the diagnostic accuracy of ultrasound in determining the level of the lesion in fetuses with open spina bifida. The secondary aim was to elucidate whether prenatal magnetic resonance imaging (MRI) improves the diagnostic performance of prenatal imaging in correctly identifying the level of the lesion. MATERIAL AND METHODS: Inclusion criteria were studies reporting the agreement between ultrasound, MRI and postnatal or postmortem assessment of fetuses with spina bifida. Agreement was defined as: complete (when the upper level of the lesion detected prenatally was the same recorded at postnatal or postmortem evaluation), within one (when the upper level of the lesion recorded prenatally was within one vertebral body higher or lower than that reported postnatally) and within two vertebral bodies (when the upper level of the lesion recorded prenatally was within two vertebral bodies higher or lower than that reported postnatally or postmortem evaluation). Meta-analyses of proportions were used to combine data. RESULTS: Fourteen studies (655 fetuses) were included. Ultrasound was able to identify the correct level of the lesion in 40.9% (95% confidence interval [CI] 26.9-55.6) of cases. The upper level of the lesion recorded on ultrasound was within one vertebral body in 76.2% (95% CI 65.0-85.9) of cases and within two segments in 92.4% (95% CI 84.3-97.7). Fetal MRI detected the exact level of the lesion in 42.5% (95% CI 35.9-45.2) of cases; the level of the lesion recorded on MRI was higher in 26.4% (95% CI 20.0-33.3) of cases and lower in 32.4% (95% CI 25.5-39.7) than that confirmed postnatally. The upper level of the lesion recorded on MRI was within one vertebral body in 76.2% (95% CI 65.9-85.2) of cases and within two segments in 94.2% (95% CI 90.2-97.2). CONCLUSIONS: Both ultrasound and MRI have a moderate diagnostic accuracy in identify the upper level of the lesion in fetuses with open spina bifida.