Minerva Medica

Gynecological cancers and urinary dysfunction: a comparison between endometrial cancer and other gynecological malignancies

The purpose of this paper is to provide a narrative overview of the available literature about voiding dysfunction in women with gynecological cancer before and after surgical, chemo- and radiotherapy treatments. Radical surgery, radiotherapy, and chemotherapy may cause lower urinary tract dysfunction such as stress and urge urinary incontinence, and voiding difficulties. However, nerve-sparing radical hysterectomy may be a valid surgical approach in order to reduce bladder innervation impairment and maintain normal urinary function. Also, newer radiotherapy techniques significantly reduce the number of adverse effects, including bladder dysfunction. Pelvic floor muscle physiotherapy and training with biofeedback and urethral bulking agents represent some additional therapies that can be used in oncologically treated patients with urinary symptoms in order to improve a significant aspect of their quality of life. Considering the important impact on the patients' quality of life, a full urogynecological evaluation should be considered as an important part of oncological treatment and follow-up.

Decoding uterine leiomyosarcoma: is ultrasound diagnosis still a daunting challenge?

This narrative review, based on the current literature, aims to evaluate whether or not preoperative ultrasound can effectively distinguish between uterine leiomyosarcomas (ULMS) and leiomyomas (ULM). By using PubMed, Scopus and WOS, an extensive literature search was conducted to identify ultrasound characteristics that specifically differentiate uterine ULMS from ULM. This review analyzed several ultrasound features to distinguish ULMS from ULM, including the maximum diameter of myometrial growth, the number of lesions (solitary/multiple), tissue echogenicity (homogeneous/heterogeneous), growth borders (regular/irregular), the presence of cystic regions, shadow presence, subjective color grading, and the vascular pattern of the myometrial lesion (circumferential/intralesional). Our findings suggest that in postmenopausal patients with abnormal uterine bleeding and a new or enlarging mesenchymal mass, ULMS should be suspected. Features such as irregular tumor margins, moderate-to-abundant intralesional blood flow, cystic regions, and lack of calcifications indicate a higher risk of ULMS. Benign and malignant myometrial lesions should be disclosed by algorithms including ultrasound combined with clinical presentations and, if necessary, magnetic resonance imaging. This means that further prospective studies should be conducted to consolidate our findings.

Sentinel lymph node for endometrial cancer treatment: review of the literature

Endometrial cancer is the most common gynecologic malignancy and in two thirds of patients it is apparently uterine confined at presentation. Lymph nodal status represents one of the main prognostic factors. Nodal evaluation with sentinel lymph node (SLN) mapping has gained more ground in clinical practice after the publication of different studies demonstrating the feasibility and accuracy of this technique. However, at the moment there are no RCTs available evaluating the long-term oncologic safety of SLN technique compared to LND. This review aims at summarizing the available evidence on oncologic outcomes between SLN mapping alone and LND. Differences in operative complications and long-term complications were also analyzed. The literature search was conducted in the PubMed database and it focused on comparative studies published from inception to September 2020 analyzing differences in oncological outcomes or complications between nodal evaluation with SLN technique alone and nodal evaluation with lymphadenectomy. Comparative studies with more than 10 cases, published in English, were included. A total of 5 retrospective comparative studies have been identified reporting data on oncologic outcomes of patients who underwent SLN mapping alone vs. LND. Non significative difference has been reported in terms of overall survival and recurrence free survival between the two groups. Six studies evaluated differences in terms of complications between the two techniques. A total of 2302 patients were identified. Postoperative complications were detected in 9.6% and 7.7% of patients who underwent lymphadenectomy and SLN mapping respectively and no significant difference was noted (P=0.3). Looking at major postoperative complications the rate in the LND group was significantly higher than in the SLN group (3.6% vs. 1.5%, P=0.02). Two of these six studies reported data on lymphatic long-term complications. The prevalence of lymphedema ranged from 0% to 1.3% in the SLN group and from 10% to 18% in the LND group. The absolute difference reported (13.35%) was similar to the one found in literature. SLN mapping in apparently uterine confined disease has been demonstrated to be a feasible and accurate technique for nodal evaluation and high-quality evidence support this. Moreover, SLN mapping resulted to be associated with less major postoperative and long-term complications when compared to LDN. Conversely, high-quality evidence is not available on long-term oncologic safety of this technique compared to the standard LND. Randomized trials are requested to provide reliable data on this aspect.

Cause analysis and nursing care of digestive tract reaction in patients with ovarian cancer during chemotherapy

LncRNA ANRIL suppresses proliferation and promotes apoptosis of ovarian cancer cells by regulating MiR-125a-3p/MAPK signaling pathway

MicroRNA-196b promotes cell growth and metastasis of ovarian cancer by targeting ZMYND11

The purpose of this study was to explore the mechanism by which microRNA-196b exerts a tumor promotion effect on ovarian cancer (OCa). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of microRNA-196b in 60 pairs of tumor samples and paracancerous ones collected from patients with ovarian cancer, meanwhile, microRNA-196b expression in human ovarian cancer cell lines and normal ovarian epithelial cell lines were also analyzed by qRT-PCR. Bioinformatics methods suggested that ZMYND11 was predicted the target gene of microRNA-196b and its binding relationship was verified by dual luciferase reporter gene experiment. Then cell counting kit (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay were performed to analyze the influence of microRNA-196b overexpression on OCa cell proliferation. QRT-PCR results showed that microRNA-196b level in OCa tissues was remarkably higher than that in normal ovarian tissues, which was closely relevant to the poor prognosis of tumors. The dual luciferase reporter gene experiments confirmed that microRNA-196b could directly bind to the 3'-UTR of ZMYND11. Overexpression of microRNA-196b remarkably enhanced the proliferation, invasiveness and migratory ability of OCa cells. Meanwhile, overexpression of microRNA-196b significantly decreased ZMYND11 mRNA and protein expression. In addition, ZMYND11 level was also significantly increased in ovarian cancer cells. Compared with the miRNA-NC group, microRNA-196b-mimics + ZMYND11-OE treatment reversed the effect of microRNA-196b-mimics on OCa cell functions. MicroRNA-196b was highly expressed in OCa tissues, which can promote the proliferation, invasiveness and migratory ability of OCa cells by targeting ZMYND11. In addition, the expression disorder of microRNA-196b was associated with the malignant development of OCa.

miR-106b exerts tumor suppressive functions in ovarian carcinoma by directly targeting ZBTB7A

Updates on endometrial cancer

Study on the main types and vaginal microecological status of persistent cervical high-risk human Papillomavirus infection in women of childbearing age

Evaluation of Light's criteria in cytologically proved malignant pleural effusions

Malignant pleural effusions are usually described as exudates. However, several studies have determined a high incidence of cytologically proved malignant effusions in transudates. The study aims to determine the compliance of cytologically proved malignant pleural effusions with Light's Criteria and to assess when it is necessary to perform more studies in transudates. We have retrospectively reviewed all the cytologically positive effusions at our institution over six years. Biochemical characteristics were recorded, and Light's criteria were determined for each effusion. We analyzed the effusions' compliance with the criteria and determined whether its primary tumor or the presence of cirrhosis, acute kidney injury or congestive heart failure could interfere in the criteria being met. Overall, 224 patients presented malignant pleural effusions with biochemical pleural fluid analysis. Two (0.9%) were transudative effusions and two hundred and twenty-two (99.1%) were exudative effusions. Lung carcinoma, breast carcinoma and ovarian carcinoma were the most frequent primary tumors. One hundred and two (45.94%) patients met three Light criteria, 77 (34.68%) patients met two criteria and 43 (19.36%) met one criterion. Both patients with transudative malignant pleural effusions presented concomitant malignant ascites. Malignant transudative pleural effusions were 0.9% of our patients. We found no relation between transudative malignant effusions and the presence of cirrhosis, acute kidney injury or congestive heart failure, or the type of tumor. We found no difference between the tumor type and the distribution of Light's criteria met.

Five case studies of ovarian cancer patients presenting pulmonary embolism

MiRNA-98 inhibits ovarian carcinoma cell proliferation, migration and invasion via targeting SALL4

MiR-127 inhibits ovarian cancer migration and invasion by up-regulating ITGA6

The effect of different doses of dexmedetomidine anesthesia on the recovery time of laparoscopic surgery for cervical cancer

Effect of psychological intervention combined with family model on postoperative rehabilitation in patients with cervical cancer

KGFR and MMP9 expression are correlates with cancer growth in cervical carcinoma

Association between HPV16 infection and expression of ERK12 signaling pathway in cervical cancer

The generally low sensitivity of CA 125 for FIGO stage I ovarian cancer diagnosis increases for endometrioid histotype

The serum marker CA 125 is still the most widely used biomarker for ovarian cancer (OC) diagnosis in gynecological and oncological setting, but its predictive role in early-stage OC is still debated. The aim of this study was to explore the value of CA 125 in distinguishing between early-stage OC and borderline ovarian tumor (BOT) and to evaluate the accuracy of CA 125 in the detection of early stage OC. A retrospective cohort study was performed at the University Hospital of Bologna (Italy) on 1296 consecutive women suffering from OC or BOT (diagnosed at histology) between 1988-2017. Patients for whom CA 125 level was determined preoperatively were included. The positive cut-off level used was >35 U/mL. Of 910 patients, 192 (21.1%) were diagnosed with BOT and 718 (78.9%) with OC. The sensitivity of CA 125 for stage I OC was 54.4 (95% CI: 45.3-63.3) (51.5 for IA, 54.6 for IB, 58.3 for IC), but it increased to 78.0 (95% CI: 63.7-88.0) for stage II. Interestingly, in stage I OC, CA 125 presented a significantly higher sensitivity for the endometrioid histotype [72.4 (95% CI: 52.5-86.5) vs. 49.0 (95% CI: 38.6-59.4), P=0.026]. The positive likelihood ratio of CA 125 for early-stage OC compared to BOT was 1.29 (95% CI: 1.06-1.58). Despite its limited sensitivity for early-stage OCs, CA 125 still represents a useful serum marker to early differentiate between OCs and BOTs. Its sensitivity for stage I OC increases in endometrioid histotype.

New development on hysteroscopy for endometrial cancer diagnosis: state of the art

Endometrial cancer (EC) is the most common gynecologic cancer diagnosed in developed countries and represents the second most frequent gynecologic cancer-related cause of death following ovarian cancer. There are 2 subtypes of EC. Type I tumors (endometrioid adenocarcinoma) representing 85-90% of the cases. They are likely to be low-grade tumors and are thought to have a link to estrogen exposure. Type II tumors represent 10-15% of EC. They are characterized as high-grade carcinomas, with serous or clear cell histology type, and carry poor prognoses. The benefits of hysteroscopy in achieving a targeted endometrial biopsy under direct visualization over blind biopsy techniques are widely accepted. Hysteroscopic endometrial biopsy is performed under direct visualization and is the only technique that allows for the selective biopsy of targeted areas of the endometrium. There is no screening protocol for the early detection of EC. Among the general population, advanced age, obesity, nulliparity and the use of exogenous hormones are known as risk factors for EC. There are additional situations that portend an increased risk of EC that deserve special consideration such as in patients diagnosed with Lynch Syndrome, using tamoxifen, obese, or the young patient with a desire for future fertility. We presented a narrative review of the current role of hysteroscopy for the diagnosis of endometrial cancer.

Histomolecular features of high-grade endometrial cancers

High-grade endometrial cancers (ECs) are an aggressive subset of ECs accounting for 70-80% of EC-related deaths. Currently, staging surgery, together with chemotherapy or radiotherapy, is the primary treatment strategy for these cancers. The widespread use of next-generation sequencing has led to a refined understanding of EC's genomics with important information for diagnosis and therapy for individual patients (precision medicine). However, advances in the genomics assessment of high-grade tumors have been slower due to their lower incidence than low-grade EC. This article will briefly introduce the current state of knowledge of the genomics of G3 endometrioid EC, serous uterine cancer, clear cell uterine carcinoma and uterine carcinosarcoma and discuss its implications for diagnosis and targeted therapy.

Study on the clinical significance of cervical conization under the guidance of colposcopy in the treatment of cervical lesions

Relationships of expressions of P16 and Ki-67 with tumor markers and prognosis of cervical cancer patients

Long noncoding RNA ZFAS1 promotes cell proliferation and tumor growth by upregulating LIN28 in cervical carcinoma

Ultra-minimally invasive approaches for endometrial cancer treatment: review of the literature

We conducted a systematic review to evaluate the outcomes and role of ultra-minimally invasive surgical approaches for treatment of women diagnosed with endometrial cancer. Although, there is no agreed definition of the term "ultraminimal," we considered the hysteroscopic surgery, single-port surgery, mini/microlaparoscopy and percutaneous laparoscopy as surgical approaches that would best fit this description. The current systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. We performed a literature search using MEDLINE (PubMed), EMBASE and Cochrane Library databases for English-language studies published before August 1, 2020. We used the following keywords including "endometrial cancer," "endometrial malignancy," "fertility-sparing or preserving," "hysteroscopy," "hysteroscopic resection," "dilatation and curettage," "ultra-minimally invasive surgery," "progestin therapy," "hormone therapy," "single port," "single-site," "minilaparoscopy," "microlaparoscopy," "percutaneous" and "3 mm laparoscopy." A total of 21 studies, reporting on 229 patients were included. 219 (95.6%) of the patients were premenopausal. Among premenopausal women, complete disease response was reported in 186 (84.9%) patients. The complete response rate was 77.1% in patients who underwent focal or extensive endometrial resection, 90.9% in patients who had the two-step approach and 88.9% in the group of patients treated with the three-step technique. Among 98 women who wished and attempted to conceive, 65 (66.3%) women became pregnant. Recurrent disease was diagnosed in 26 of 219 (11.9%) patients. No surgical complications were reported. In 10 postmenopausal patients that underwent hysteroscopic resection, no recurrences were detected after 5 years of follow-up. We identified 11 studies that reported on the use single-port laparoscopic surgery and included a total of 447 patients. The rate of intraoperative and postoperative complications was 2.6% and 5.2%, respectively. The majority of the studies did not report on the duration of follow-up or oncological outcomes. Ten studies, including 296 patients, investigated the role of single-port robotic-assisted laparoscopy. The overall rate of intraoperative and postoperative complications was 1.0% and 7.1%, respectively. Two studies, including 38 patients, reported on the role of minilaparoscopy. None of these cases required conversion to laparotomy. Data on overall survival in the cohort of patients that underwent minilaparoscopy were not reported. We found only one publication reporting on the use of percutaneous laparoscopy. This prospective study included 30 patients. No complication was reported, and with a median follow-up time of 14 months (range 12-36) no recurrences were diagnosed. Several ultra-minimally invasive surgical techniques have been developed and implemented in selected patients with endometrial cancer. The results of this review support the feasibility and perioperative safety of these approaches, while long-term outcomes are not adequately studied. However, further work is required in standardization of the techniques, in determining the learning curve of the operator and establishing their oncological safety.

Fertility-sparing management for endometrial cancer: review of the literature

Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management in the case of atypical endometrial hyperplasia, or grade 1 EC limited to the endometrium can be considered. We performed a literature review to identify studies involving women with EC or atypical hyperplasia who underwent fertility-sparing management. We conducted multiple bibliographic databases research from their inception to May 2020. Oral therapy with medroxyprogesterone acetate and megestrol acetate is recommended based on extensive experience, although without consensus on dosages and treatment length. The pooled complete response rate, recurrence rate, and pregnancy rate of EC were 76.3%, 30.7% and 52.1%, respectively. Endometrial hyperplasia was associated with better outcomes. LNG-IUSs appears an alternative treatment, particularly in patients who do not tolerate oral therapy. In a randomized controlled trial, megestrol acetate plus metformin guaranteed an earlier complete response rate than megestrol acetate alone for endometrial hyperplasia. Hysteroscopic resection followed by progestogens is associated with a higher complete response rate, live birth rate, and lower recurrence rate than oral progestogens alone. Pooled complete response, recurrence, and live birth rates were 98.1%, 4.8% and 52.6%. Fertility preservation appears feasible in young patients with grade 1 EC limited to the endometrium or atypical endometrial hyperplasia. Progestins are the mainstay of such management. The addition of Metformin and hysteroscopic resection seems to provide some improvements. However, fertility preservation is not the standard approach for staging and treatment, potentially worsening oncologic outcomes.

Robotic platforms for endometrial cancer treatment: review of the literature

The cornerstone in the management of endometrial cancer (EC) is surgical staging. Over the last few decades, minimally invasive surgery has been widely accepted as a mainstay in the treatment of endometrial cancer. The first robotic-assisted gynecological surgery was performed in 1998. The literature search was conducted using MEDLINE, EMBASE and PUBMED databases from January 1998 to September 2020. Several studies have reported the advantages of robotic-assisted surgery over laparoscopy in the management of EC. These are most pronounced in obese patients. Robotic-assisted surgery is also associated with a shorter learning curve, particularly for lymphadenectomy, which enables more surgeons to perform minimally invasive surgery for EC. The effectiveness and oncological results of robotic surgery for EC appear to be similar to those of other surgical methods, but fewer intraoperative complications occur than with other methods.

Novelties of ultrasound imaging for endometrial cancer preoperative workup

Endometrial cancer (EC) is the most frequent gynecological cancer. Transvaginal ultrasound (TVU) plays a leading role in the preoperative workup and often is the first diagnostic instrumental examination. Despite expert hands' ultrasound is recommended to assess myometrial invasion in early stage EC, this method is a strictly operator-dependent examination, and varying degrees of sensitivity and specificity have been reported. The present review aims to provide an update of ultrasound imaging in the preoperative work-up for EC patients. A double-blind search was performed from May to September 2020. The following keywords: "ultrasound," "transvaginal ultrasound" and "endometrial cancer" were searched in Pubmed search engines, Scopus, and Web of Science. The Prisma statement was followed for the selection of the articles included. The initial search provided 958 studies, of which 11 were included in the analysis. non-English articles, not relevant to the purposes of this study, case reports and articles with fewer than 40 cases were excluded. TVU sensitivity and specificity in myometrial infiltration and cervical invasion is comparable to MRI but has lower costs, greater patient tolerability, and does not require contrast agents. An expert operator should perform the ultrasound examination in patients with suspected EC The presence of myometrial lesions, such as leiomyomas, could lower the diagnostic accuracy of ultrasound, so special attention should be paid to patients with concomitant uterine lesions.

Quality of life and sexual functioning of patient affected by endometrial cancer

Thanks to timely diagnosis and medical advancement the number of endometrial cancer (EC) patients achieving long term survival is constantly increasing and here comes the necessity to move forward with the understanding of post-treatment sexual adjustment and with the strategies to enhance sexual functioning (SF) and quality of life (QoL) in this population. In this scenario we designed this study aiming to summarize and analyze the available scientific evidence regarding QoL and especially SF in patients affected by EC who underwent surgical and adjuvant treatment. A preliminary research was conducted using Pubmed database with specific keywords combinations regarding SF, QoL and endometrial cancer. The main findings considered in the present review were: the study design, the number of patients included in each study, the information about pathology (histology and stage of disease), the questionnaires administered and the principal results concerning SF and QoL. A total of thirteen studies, between 2009 and 2018, treating the aspects of SF and QoL in patients affected by EC were extracted. The principal findings of different studies were organized in the following sections: 1) overall SF in EC patients (reasons for sexual inactivity); 2) impact of EC on SF when compared to benign gynecological disease or healthy controls-focus on surgery; 3) minimally invasive surgery versus classical laparotomic approach and SF of EC patients; 4) surgery alone versus VBT versus EBRT and SF of EC patients; 5) focus on RT; 6) the mutual correlation between sociodemographic, relational, psychological, clinical/metabolic factors and the SF of EC patients. Considering the widespread diffusion of female sexual dysfunction among EC patients and the relatively good prognosis, especially in early stage disease, it undoubtedly looms the need for proactive countermeasures to maximize the sexual well-being and QoL of these patients. A wide range of intervention in a multi-modal physical and mental perspective should be considered.