Erroneous presentation of respiratory-hemodynamic disturbances and postsurgical inflammatory responses in patients having undergone abdominal cavity cancer surgery.

In this letter to the editor, the authors discuss the findings and shortcomings of a published retrospective study, including 120 patients undergoing surgery for gastric or colon cancer under general anesthesia. The study focused on perioperative dynamic respiratory and hemodynamic disturbances and early postsurgical inflammatory responses.

Myomectomy in adult women of reproductive age: a propensity score-matched study for pregnancy rates.

PURPOSE: To study whether it is better to perform or not a myomectomy, in terms of surgical and reproductive outcomes in patients of advanced reproductive age, by an observational prospective study in university-affiliated and Community Hospitals. MATERIALS AND METHODS: 40 years and older patients affected by non-submucous symptomatic uterine fibroids and desiring future fertility were enrolled and treated by laparoscopic intracapsular myomectomy by (LIM) or by open laparotomy (OIM), or by a non-surgical management as control group, while attempting to conceive. The primary outcome measures were fibroid characteristics, pre- and post-surgical parameters, pregnancy achievement; the secondary outcome measures were the spontaneous or ART pregnancy outcomes, eventual week of abortion and type of delivery. Propensity scores have been calculated with logistic regression for binary and continuous variables. RESULTS: 202 patients completed the study: 112 operated by LIM, 40 by OIM and 50 patients as control group. Patients undergoing OIM have a worse surgical outcome than LIM. No difference was seen in pregnancy either after myomectomy or control group during follow-up. In the LIM group, there were 44 pregnancies (39.2%), and in the OIM group, there were 9 (22.5%) and 16 in the control group (32%). The weeks of delivery were statistically greater for the control group versus the surgical groups, with no difference in Apgar score between the 3 groups. CONCLUSION: Patients aged over 40 years did not show substantial differences in reproductive outcome, whether operated or not. Myomectomy in over 40-year-old patients has no detrimental effect on future pregnancy rates and over when compared to expectant management.

COVID-19-The Shift of Homeostasis into Oncopathology or Chronic Fibrosis in Terms of Female Reproductive System Involvement.

The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus remains a global public health concern due to the systemic nature of the infection and its long-term consequences, many of which remain to be elucidated. SARS-CoV-2 targets endothelial cells and blood vessels, altering the tissue microenvironment, its secretion, immune-cell subpopulations, the extracellular matrix, and the molecular composition and mechanical properties. The female reproductive system has high regenerative potential, but can accumulate damage, including due to SARS-CoV-2. COVID-19 is profibrotic and can change the tissue microenvironment toward an oncogenic niche. This makes COVID-19 and its consequences one of the potential regulators of a homeostasis shift toward oncopathology and fibrosis in the tissues of the female reproductive system. We are looking at SARS-CoV-2-induced changes at all levels in the female reproductive system.

The impact of cervical conization size with subsequent cervical length changes on preterm birth rates in asymptomatic singleton pregnancies.

The study aimed to explore the impact of cervical conization size (CCS) with subsequent cervical length (USCL) changes on preterm birth (PTB) rates in asymptomatic singleton pregnancies as compared to pregnancy outcomes in healthy women with an intact cervix (ICG), and to estimate PTB prevention efficiency in patients with a short cervix. Pregnancy outcomes in populations of similar age, ethnicity, residency, education and harmful habits having undergone cervical conization (CCG) were retrospectively analyzed and compared to ICG and cervical conization sub-populations adjusted by USCL during pregnancy (adequate cervical length vs. a short cervix) and a progesterone-only group (POG) vs. a progesterone-pessary group (PPG). Cervical conization was not associated with an increased PTB risk (CCG vs. ICG) when parameters of CCS and USCL were not adjusted (p = NS). A significantly higher proportion of parous women was observed in the CCG population than in the ICG (p = 0.0019). CCS turned out to be a key PTB risk during pregnancy, the larger CCS being associated with a short cervix (p = 0.0001) and higher PTB risks (p = 0.0001) with a notably increased PTB rate (p = 0.0001) in nulliparous women (p = 0.0022), whereas smaller CCS with adequate cervical length and a lower PTB rate was predominantly observed in women with prior parity. An initial equal USCL size was to be considerably elongated in women with adequate cervical length (p < 0.0001), and shortened in those with a short cervix (p < 0.0001). USCL assessment during pregnancy proved to be the PTB risk-predicting tool, with CCS supplementation apt to increase its diagnostic value. No substantial impact on pregnancy outcomes could be linked to any particular PTB prevention mode (POG or PPV). However, during pregnancy, the USCL changes relating to CCS proved to be more critical in pregnancy outcomes.

Laparoscopic Intracapsular Myomectomy in Women 40 Years Old and Over with Symptomatic Uterine Fibroids. A Pilot Study.

Authors evaluated the impact of laparoscopic intracapsular myomectomy (LIM) in women 40 years of age and over with desire of future fertility compared with medical management of symptomatic fibroids, by a prospective cohort study in University affiliated Hospitals. This study includes a cohort of women 40 years of age and older with symptomatic intramural fibroids with desire of future fertility. Women with symptomatic fibroid uterus were offered to undergo LIM or medical management. They were encouraged to attempt conception either spontaneously or by assisted reproductive technology (ART) according to their individual preference. All women were followed for 2 years. Fibroid characteristics, pre- and post-surgical variables, including surgical complications, days of hospitalization, pregnancy rate, and obstetrical outcomes were collected. A total of 100 patient were included in the analysis. Fifty patients were assigned to the LIM group and 50 to the medical treatment group (MT). Groups were similar regarding age (43.5 ± 2.4 and 43.5 ± 2.4, p = 0.99), body mass index (23.8 ± 3.1 and 24.2 ± 3.1, p = 0.54), parity (0.46 ± 0.09 and 0.58 ± 0.09, p = 0.37), fibroid number (1.38 ± 0.6 and 1.46 ± 0.6, p = 0.53), and fibroid size (5.92 ± 1.62 cm vs. 5.94 ± 1.49 cm, p = 0.949). Of the patients who underwent LIM, 62% conceived within the study period compared with 56% in the control group ( p = 0.54). Pregnancy was achieved by ART in 44% of the patients of the LIM group and 30% in control group. There was no significant difference in pregnancy rates among the two groups regarding spontaneous pregnancy rate ( p = 0.332), nor in pregnancies obtained by ART with own eggs ( p = 0.146) and oocyte or embryo donation ( p = 0.821). The take home baby rate was 65% (20/31) in the LIM group and 61% (17/28) in the control group ( p = 0.7851). Both groups had similar rate of miscarriage ( p = 0.748). Patients 40 years old and over with symptomatic fibroid uterus who undergo LIM have similar subsequent fertility and obstetrical outcomes than women treated with medical management. LIM has no detrimental impact on future fertility in women 40 years old and over.

Human Papillomavirus Selected Properties and Related Cervical Cancer Prevention Issues.

High-risk human papillomavirus strains are widely known to be the causative agents responsible for cervical cancer development. Aggregated damage caused by papillomaviruses solely is estimated in at least 5% of all malignancies of the human body and 16% in cancers that affect the female genital area. Enhanced understanding of the complex issue on how the high extent of carcinogenicity is eventually formed due to the infection by the Papoviridae family would contribute to enhancing current prevention strategies not only towards cervical cancer, but also other HPV associated cancers. This review article is aimed at presenting the key points in two directions: the current cervical cancer prevention and related aspects of HPV behavior. Virtually all applied technologies related to HPV diagnostics and screening programs, such as HPV tests, colposcopy-based tests (VIA/VILI), conventional and liquid-based cytology, currently available are presented. Issues of availability, advantages, and drawbacks of the screening programs, as well as vaccination strategies, are also reviewed in the article based on the analyzed sources. The current point of view regarding HPV is discussed with emphasis on the most problematic aspect of the HPV family concerning the observed increasing number of highly carcinogenic types. Present trends in HPV infection diagnostics throughout the human fluids and tissues are also reported, including the latest novelties in this field, such as HPV assay/self-sample device combinations. Besides, a brief outline of the related prevention issues in Kazakhstan, the leading country of Central Asia, is presented. Kazakhstan, as one of the post-soviet middle-income countries, may serve as an example of the current situation in those terrains, concerning the implementation of globally accepted cervical cancer prevention strategies. Along with positive achievements, such as the development of a nationwide screening program, a range of drawbacks is also analyzed and discussed.

Adrenergic and Cholinergic Uterine Innervation and the Impact on Reproduction in Aged Women.

In recent years, the development of Assisted Reproductive Technique, the egg and embryo donation changed substantially the role of the uterus in recent years. It provided a higher chance for a pregnancy even in women over 45 years or post-menopause. In fact, the number of aged patients and in peri/post-menopause in pregnancy is nowadays increasing, but it increases obstetrical and neonatal related problems. The human uterus is richly innervated and modified especially during pregnancy and labor, and it is endowed with different sensory, parasympathetic, sympathetic and peptidergic neurofibers. They are differently distributed in uterine fundus, body and cervix, and they are mainly observed in the stroma and around arterial vessel walls in the myometrial and endometrial layers. Many neurotransmitters playing important roles in reproductive physiology are released after stimulation by adrenergic or cholinergic nerve fibers (the so called sympathetic/parasympathetic co-transmission). Immunohistochemical study demonstrated the localization and quantitative distribution of neurofibers in the fundus, the body and cervix of young women of childbearing age. Adrenergic and cholinergic effects of the autonomous nervous system are the most implicated in the uterine functionality. In such aged women, the Adrenergic and AChE neurofibers distribution in the fundus, body and cervix is progressively reduced by increasing age. Adrenergic and AChE neurotransmitters were closely associated with the uterine arteries and myometrial smooth muscles, and they reduced markedly by ageing. The Adrenergic and AChE neurofibers decreasing has a dramatical and negative impact on uterine physiology, as the reduction of pregnancy chance and uterine growth, and the increase of abortion risk and prematurity.

The Medical Device Applied to Uterine Fibroids Morcellation: Analysis of Critical Biological Issues and Drawbacks from A Medical-Legal Prospective.

Following the FDA safety communication of 2014 increasing attention has been to the treatment of uterine fibroids, due to the suspicion of a potential leiomyosarcoma (ULM). FDA banned the use of power morcellation in the US, since this technique is likely to spread malignant cells from an unsuspected ULM. We criticized the medical legal consequences of this banning among gynecologists and patients, focusing on the drawbacks of biology and surgery. The authors analyzed literature data on one side, on the incidence, diagnosis and treatment of leiomyoma and ULM, and the other side, on the power morcellations and related critical issues, trying to highlight their main controversial aspects and to outline the possible impact on patients and on medical responsibility. The alternative methods to power morcellation are more invasive surgical solutions (as mini laparotomy or culdotomy), which inevitably involve associated risks with the surgical procedure as such and always request the containing bags. Although the in-bag morcellation is a promising technique, currently the used devices are largely off-label. This highlights the surgical risk, in case of complications, of suffering for malpractice claims both for not having used a containment system, favoring the spread of the neoplasm, and for its off-label use. Since the diagnosis of ULM is by histology after surgery, the fear of legal consequences or medical malpractice for unknown ULM power morcellation, should be targeted to analyze, in terms of cost/benefit ratio, the surgical priority. It should focus on the prevention of the risk of having a rare and statistically limited ULM or on the surgical-related complications, often linked to a slowdown minimally invasive surgery, or on the use of the authorized in-bag morcellations.

The Biological Impact of Ulipristal Acetate on Cellular Networks Regulating Uterine Leiomyoma Growth.

Uterine Fibroids (UFs), or leiomyomas, represent the most frequent pelvic tumor in reproductive-aged women. Although of benign origin, UFs decrease fertility and cause significant reproductive dysfunctions. Compared to normal myometrium, UFs are characterized by a clinical and molecular heterogeneity as demonstrated by the presence of multiple genetic alterations and altered signaling pathways. Recently, selective progesteronereceptor modulators (SPRM), as ulipristal acetate (UPA), have demonstrated their clinical benefits by reducing tumor growth and extracellular matrix deposition. For these reasons, UPA is used in the clinical practice as an intermittent treatment for women symptomatic for UFs or, sometimes, before a myomectomy. However, drug effects on signaling pathways frequently upregulated in UFs remain largely unknown. In fact, the mechanisms of action of the UPA on UFs and on the surrounding areas are not yet understood. To learn more about UPA molecular mechanisms, UF samples were treated ex vivo with UPA and profiled for drug effects on selected markers. During this preliminary ex vivo UPA administration, significant changes were observed in the expression levels of proteins related to cell cycle regulation, cytoskeleton remodeling, and drug resistance. The UPA administration reduced cofilin, Erk and Src phosphorylation, p27 and ezrin protein levels, but not Akt phosphorylation and cyclin D1 and ß-catenin levels. This preliminary ex vivo biological analysis provided new insights into the mechanism of action of UPA in the treatment of UFs, which could better explain the biological functioning of the drug on UFs.

The Extracellular Matrix-Derived Biomarkers for Diagnosis, Prognosis, and Personalized Therapy of Malignant Tumors.

The tumor biomarkers already have proven clinical value and have become an integral part in cancer management and modern translational oncology. The tumor tissue microenvironment (TME), which includes extracellular matrix (ECM), signaling molecules, immune and stromal cells, and adjacent non-tumorous tissue, contributes to cancer pathogenesis. Thus, TME-derived biomarkers have many clinical applications. This review is predominately based on the most recent publications (manuscripts published in a last 5 years, or seminal publications published earlier) and fills a gap in the current literature on the cancer biomarkers derived from the TME, with particular attention given to the ECM and products of its processing and degradation, ECM-associated extracellular vesicles (EVs), biomechanical characteristics of ECM, and ECM-derived biomarkers predicting response to the immunotherapy. We discuss the clinical utility of the TME-incorporating three-dimensional in vitro and ex vivo cell culture models for personalized therapy. We conclude that ECM is a critical driver of malignancies and ECM-derived biomarkers should be included in diagnostics and prognostics panels of markers in the clinic.

Submucous Fibroids, Fertility, and Possible Correlation to Pseudocapsule Thickness in Reproductive Surgery.

BACKGROUND AND OBJECTIVES: Fibroids are related to infertility. Fibroid pseudocapsule is a neurovascular bundle surrounding leiomyomas rich of neurofibers involved in myometrial biology. Authors evaluated, by a case-control study, the fibroid pseudocapsule (FP) thickness by ultrasound (US) and the histological measurements, according to uterine location of fibroids. METHODS: 137 consecutive patients undergoing hysterectomy for uterine myomas were enrolled and 200 myomas were evaluated. Before surgery, patients underwent an ultrasound (US) investigation to evaluate the number, the size, and the location of fibroids. After surgery, myoma-pseudocapsule-myometrium specimens were measured and evaluated by a single expert pathologist. Both US and histological data were collected and statistically analyzed. RESULTS: Our results confirm the relevant difference of FP thickness, particularly represented under the endometrium for submucous LMs. FPs near the endometrial cavity were considerably thicker than those of both intramural fibroids and subserous fibroids measured by US (P=0.0001) and histology (P=0.0001). A clear cut-off measurement at 2 mm (P=0.0001) was found between endometrial FPs and all other FPs for either US or histology measurements. CONCLUSION: The thickness of FP is considerably higher near the endometrial cavity when compared to those of both intramural and subserous LMs, suggesting a potential role either in fertility or in myometrial healing.