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The rectovaginal septum is a rare location for gastrointestinal stromal tumors (GIST) to occur. The aim of this study was to present a case of synchronous local recurrence of solitary liver metastasis originating from an extra gastrointestinal tumor (E-GIST) of the rectovaginal space. A 55-year-old woman, with a medical history of a resected meningioma, was referred to our department due to a 5 cm solitary liver metastasis located within the left lateral segment. The patient had undergone a transvaginal resection of a low-risk E-GIST 6 months prior without receiving adjuvant chemotherapy. The patient underwent a synchronous laparoscopic left lateral hepatectomy and a transvaginal resection with posterior vaginal wall reconstruction. Her postoperative course was uneventful and was discharged on the fifth postoperative day. The histological examination of the vaginal lesion revealed the development of neoplasm with pathological characteristics consistent with the initial histology expect for a mitotic index exceeding >20%. Liver histology report also included a high-risk GIST with CKIT (+), DOG1 (+), ki67 ≥30%, high mitotic activity and clear resection margins. The patient was referred for adjuvant chemotherapy. E-GISTs are rare neoplasms with low malignant potential. However, these tumors may exhibit metastatic potential and require aggressive treatment.

Paraovarian tumors of borderline malignancy (PTBM) are exceedingly rare, with only slightly over 60 cases reported worldwide. This report presents the case of a 22-year-old nulliparous patient who incidentally discovered a left paraovarian mass during a routine abdominal ultrasound. Subsequent MRI revealed a 2.5×2.1 cm cystic lesion located in close proximity to, but outside of, the left ovary, with no other pathological findings. A laparoscopic cystectomy was performed with meticulous care to prevent tumor spillage, and the patient experienced an uneventful recovery. Histopathological examination unveiled irregularly shaped tissue measuring 2.2×1.2×1 cm, characterized by fibrous tissue/wall with spindle cell stroma and an epithelium displaying features consistent with a serous borderline tumor. Our multidisciplinary team recommended diligent follow-up. This case contributes to the existing literature on PTBM and highlights the imperative for additional cases to enhance our comprehension of the optimal management of these exceedingly rare tumors.

Abstract Background Several variables influence the serum concentration of thyroid hormones in dogs, including breed, age, drugs, and concurrent diseases. However, data regarding the interaction between thyroid function and the estrous stage of female dogs are limited. Hypothesis Estrous stage may influence thyroid function in German Shepherd dogs. Methods Longitudinal, observational, non‐randomized cohort study. The dogs were monitored during the complete estrous cycle, and different stages were determined by vaginal cytology. Two blood samples were collected at the beginning and end of each stage to analyze the following: total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3), canine thyrotropin (cTSH), progesterone, 17‐β‐estradiol, triglycerides, and cholesterol concentrations. Hematological and biochemical evaluations were performed at the beginning and end of the study period. Animals Seventeen German Shepherds were included, of which 7 were bred during the study period. One dog was excluded for estrus interruption and another for suspected hypothyroidism. Results Serum concentrations of T4, fT4, and fT3 were negatively correlated with age. Total thyroxine demonstrated significant changes in serum concentrations between estrous stages, with higher concentrations in estrus and diestrus. Total thyroxine concentrations were positively correlated with progesterone concentrations and negatively correlated with 17‐β‐estradiol concentrations. Free thyroxine did not show significant variations but was positively correlated with progesterone concentrations. Canine TSH concentrations were positively correlated with 17‐β‐estradiol concentrations. No significant differences in thyroid hormones and cTSH concentrations were observed between diestrus during pregnancy and pseudopregnancy. Conclusions Different stages of estrus can influence the measurement of TT4 in female dogs.

Background: Isolated mediastinal metastases from ovarian carcinoma are considered exceptional. Since such metastases are considered advanced stage disease, systemic therapy is the indicated therapeutic approach; however, some articles report that surgical excision is also feasible. Methods: We reviewed the English-language literature to detect cases of isolated mediastinal ovarian cancer metastases and present the management applied as well as their outcomes. Results: From 1998 to 2022, 15 such cases have been reported, with 4 of those cases being primary ovarian cancer presentation and 11 being ovarian cancer recurrence. The histology of the tumor was serious in all of the cases. Regarding the management of cancer, various methods were applied. In total, 11 of the patients underwent a surgical resection of the mediastinal metastasis, 2 received systemic therapy, 1 received a combination of palliative chemotherapy and radiation and the last patient was treated with laser debulking and radiotherapy. The mean reported follow-up was 11 months. Conclusions: Solitary mediastinal metastasis from ovarian cancer is very rare; physicians should pay close attention when routinely evaluating thoracic scans from patients with ovarian malignancy as well as individualizing the management in such patients, since surgical resection can also be performed. However, definitive conclusions cannot be drawn from the small number of case reports available.

Panagiotis Peitsidis,1 Panagiotis Tsikouras,2 Antonio Simone Laganà,3 Alexandros Laios,4 Ioannis D Gkegkes,5 Christos Iavazzo6 1Department of Obstetrics and Gynecology Helena Venizelou Hospital, Athens, Greece; 2Department of Obstetrics and Gynecology.The Democritus University of Thrace, Alexandroupolis, Greece; 3Unit of Gynecologic Oncology ARNAS “Civico-Di Cristina-Benfratelli”, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Palermo, Italy; 4Department of Gynecological Oncology St James Institute of Oncology, Leeds Teaching Hospitals, Leeds, Uk; 5Department of Colorectal Surgery, Royal Devon and Exeter NHS Foundation, Devon, UK; 6Gynaecological Oncology Department, Metaxa Cancer Hospital, Piraeus, GreeceCorrespondence: Panagiotis Peitsidis, Department of Obstetrics and Gynecology, Helena Venizelou Hospital Athens Greece, Helena Venizelou 2 Street, P.C, Athens, 11521, Greece, Tel +306972221553 ; +302107473793, Email peitsidiobgyn@gmail.comAbstract: Endometriosis is a chronic gynecologic condition that affects around 6– 10% of reproductive age women. This clinical entity is characterized with pelvic pain, dysmenorrhea, dyspareunia, and infertility which are the most often presenting symptoms. Aromatase P450 is the key enzyme for ovarian estrogen biosynthesis and there is evidence that endometriotic lesions express aromatase and are able to synthesize their own estrogens. Aromatase inhibitors (AIs) are potent drugs that suppress the estrogen synthesis via suppression of aromatase. We performed a systematic review of systematic reviews and narrative reviews on the use of aromatase inhibitors in the medical management of endometriosis. We searched: PubMed (1950– 2022), Google Scholar (2004– 2022), Cochrane Library (2010– 2022) and Researchgate (2010– 2022). The search included the following medical subject headings (MeSH) or keywords: “Aromatase Inhibitors” AND “Endometriosis” AND “Systematic reviews” OR “Systematic review” AND “Reviews” OR “Reviews” AND “Endometriosis”. The electronic database search yielded initially 12,106 studies from the different databases. Further assessment of the studies resulted in exclusion of (n = 12,015) studies due to duplicates and irrelevance; Finally, 24 studies were selected for inclusion, 5 were Systematic reviews and 19 were Narrative reviews. The 5 systematic reviews were assessed by AMSTAR-2 criteria and were found to have low quality. Narrative reviews were assessed with SANRA criteria and were found to have high-quality aromatase inhibitors are potent drugs that can manage the endometriosis-related symptoms in cases where initial medical management has failed to show positive results. However, their use is limited by the adverse effects that are linked with menopausal symptoms. aromatase inhibitors can be administered as an alternative treatment in patients. Future studies with randomized design are required to reach safer conclusions and further investigation. These studies should define the therapeutic dose, new add-back therapy modalities. Future directions should examine the most-appropriate way of administration and the duration of therapy.Keywords: endometriosis, aromatase inhibitors, systematic review, pelvic pain, adverse effects

Abstract Background Tumor-initiating cells (TIC), also known as cancer stem cells, are considered a specific subpopulation of cells necessary for cancer initiation and metastasis; however, the mechanisms by which they acquire metastatic traits are not well understood. Methods LAMC2 transcriptional levels were evaluated using publicly available transcriptome data sets, and LAMC2 immunohistochemistry was performed using a tissue microarray composed of PDAC and normal pancreas tissues. Silencing and tracing of LAMC2 was performed using lentiviral shRNA constructs and CRISPR/Cas9-mediated homologous recombination, respectively. The contribution of LAMC2 to PDAC tumorigenicity was explored in vitro by tumor cell invasion, migration, sphere-forming and organoids assays, and in vivo by tumor growth and metastatic assays. mRNA sequencing was performed to identify key cellular pathways upregulated in LAMC2 expressing cells. Metastatic spreading induced by LAMC2- expressing cells was blocked by pharmacological inhibition of transforming growth factor beta (TGF-β) signaling. Results We report a LAMC2-expressing cell population, which is endowed with enhanced self-renewal capacity, and is sufficient for tumor initiation and differentiation, and drives metastasis. mRNA profiling of these cells indicates a prominent squamous signature, and differentially activated pathways critical for tumor growth and metastasis, including deregulation of the TGF-β signaling pathway. Treatment with Vactosertib, a new small molecule inhibitor of the TGF-β type I receptor (activin receptor-like kinase-5, ALK5), completely abrogated lung metastasis, primarily originating from LAMC2-expressing cells. Conclusions We have identified a highly metastatic subpopulation of TICs marked by LAMC2. Strategies aimed at targeting the LAMC2 population may be effective in reducing tumor aggressiveness in PDAC patients. Our results prompt further study of this TIC population in pancreatic cancer and exploration as a potential therapeutic target and/or biomarker.

Background and Objectives: Available evidence reports the overexpression of β1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of β1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10–25%, 1+ (weak); 25–50%, 2+ (medium); ≥50%, and 3+ (high)) for β1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher β1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: β1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

Background: Despite the considerable progress made in recent years in fetal assessment, the etiology of fetal growth disturbances is not as yet well understood. In an effort to enhance our knowledge in this area, we investigated the associations of the amniotic fluid angiotensinogen of the renin–angiotensin system with fetal growth abnormalities. Methods: We collected amniotic fluid samples from 70 pregnant women who underwent amniocentesis during their early second trimester. Birth weight was documented upon delivery, after which the embryos corresponding to the respective amniotic fluid samples were categorized into three groups as follows: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Amniotic fluid angiotensinogen levels were determined by using ELISA kits. Results: Mean angiotensinogen values were 3885 ng/mL (range: 1625–5375 ng/mL), 4885 ng/mL (range: 1580–8460 ng/mL), and 4670 ng/mL (range: 1995–7250 ng/mL) in the SGA, LGA, and AGA fetuses, respectively. The concentrations in the three groups were not statistically significantly different. Although there were wide discrepancies between the mean values of the subgroups, the large confidence intervals in the three groups negatively affected the statistical analysis. However, multiple regression analysis revealed a statistically significant negative correlation between the angiotensinogen levels and gestational age and a statistically significant positive correlation between the birth weight and angiotensinogen levels. Discussion: Our findings suggest that fetal growth abnormalities did not correlate with differences in the amniotic fluid levels of angiotensinogen in early second trimester pregnancies. However, increased angiotensinogen levels were found to be consistent with a smaller gestational age at birth and increased BMI of neonates.

Uterine angiolipoleiomyomas are rare, benign mixed mesenchymal lesions. A manifestation in the gynecological region is quite uncommon, with few cases described in the literature so far. We present an interesting case of a 59-year-old woman diagnosed with uterine angiolipoleiomyoma, and the results of the conducted systematic review of the literature. The patient presented with a pelvic mass masquerading as a leiomyoma on the ultrasound and postmenopausal vaginal bleeding. At laparotomy, a large uterus was noticed and the histopathology set the diagnosis of angiolipoleiomyoma. Immunohistochemistry revealed negativity for Melan-A and HMB-45 melanoma-specific antibodies and positivity for Van Gieson and orcein histochemical stains. We systematically reviewed the literature. The eligible articles were those written in English, excluding animal studies and studies reporting angiolipoleiomyomas in other regions beside the uterus. The present case is one of the 10 cases of uterine angiolipoleiomyoma reported in the literature. In 8 out of 11 (72.7%) cases, uterine angiolipoleiomyomas arose from the corpus of the uterus, while in 2 (18.1%) cases they were located at the cervix, and in one case (9%) angiolipoleiomyoma was located in the broad ligament. Concerning symptoms, four of the patients (36.4%) presented with abdominal and pelvic pain, two (18.1%) with postmenopausal vaginal bleeding, one with menometrorrhagia (9%), and one with uterine prolapse and cystocele (9%). Immunohistochemical staining of uterine angiolipoleiomyomas was positive for SMA in 4 patients (36.4%), positive for desmin in 3 cases (27.3%), positive for anti-S-100 protein antibody in 2 patients (18.1%), while in one case (9%) immunopositivity was observed for CD31. Only our case (9%) was also tested for CD34, Van Gieson and orcein, the first of these being negative and the other two positive (at the blood vessels in a specialized pattern). Three of the patients (27.3%) were also tested for HMB-45 and all three were immunonegative. In order to establish the diagnosis of uterine angiolipoleiomyomas, ultrasonography and additional MRI may help the preoperative prediction of a benign mass. Immunohistochemistry will show strong positivity of alpha-smooth muscle actin and desmin. Complete abdominal hysterectomy is the preferable treatment.

Crohn’s disease is a multi-systemic chronic inflammatory disease that can affect various organs besides the gastrointestinal tract such as joints, uvea, and the skin. Vulvar Crohn’s disease is a rare entity occurring with vulvar lesions that show typical Crohn’s disease granulomatous inflammation but are not contiguous with the gastrointestinal involvement. Vulvar Crohn’s disease can be easily confused with other granulomatous diseases and awareness that such involvement may precede gastrointestinal symptoms must be raised. Few cases of vulvar Crohn’s disease have been reported in the literature to date. Here, we report a case of a 43-year-old woman with a 6-month history of a vulvar lesion; the patient was diagnosed with Crohn’s disease of the large bowel just over a year ago.

Broad mountainous areas in the western Campania (southern Italy), where young pyroclastic deposits extensively outcrop, frequently experience rainfall-induced slope movements of different degrees of mobility, causing heavy damage and fatalities. Such landslides cannot be easily mitigated, and the implementation of physically based early warning systems is still not able to predict the post-failure evolution of slope movements and the exposed areas at risk. This paper is devoted to overcoming this limit. To this end, the mechanical characterization of pyroclastic soil, carried out through an extensive laboratory testing program, is presented and compared with those of two other ashy soils of different depositional mechanisms. The results show that the depositional mode influences soil properties; to begin with, it affects the unsaturated shear strength, whose intercept of cohesion is up to 5 kPa higher in ashes of flow deposition than in airfall ash deposits. The saturated undrained soil response allowed for the identification of different levels of susceptibility to the liquefaction of pyroclastic deposits, which is one of the main factors governing the post-failure evolution of landslides. Gathering all the acquired information, including saturated and unsaturated soil shear strength, permeability function, and water retention curves, into a soil database, it was possible to present all data under a unitary framework. Finally, the implementation of the proposed flowchart for a simplified assessment of post-failure evolution to be employed in regional early warning systems can enhance our knowledge of the areas at risk.

The change in life expectancy affects the clinical presentation and the prognosis of elderly patients with gynecological cancer. The in-crease of life expectancy and increased numbers of elderly patients, the healthcare systems have to deal more frequently with patients who are not simply older adults but have also severe comorbidities and physiological, psychological, functional, and social needs that require individualised management. Discussing every individual after detailed assessment in a multidisciplinary meeting is extremely important. Several studies have shown that elderly patients with gynecological malignancies are not treated to the same extent as young-er patients and have lower odds of receiving standard care according to the oncological protocols. Individualization of management in these patients could be identified in several studies in the literature showing that increasing age at diagnosis predicts deviation from guidelines for surgical therapy, adjuvant radiotherapy or chemotherapy. The authors performed a literature review to clarify whether there are any changes in the treatment of such patients, and whether their management should be considered to be individualized, depending on their age and comorbidities.

Fibroids are the most common benign tumors affecting fertility and quality of life. Different methods either definitive or fertility sparing are used for their management by using open, laparoscopic and robotic techniques. This is a narrative review presenting the role and the advantages of robotic surgery in fibroids (myomectomies or hysterectomies). Such a management is effective, safe and feasible in hands of well-trained teams even for multiple, large or deep located fibroids.

Background: Isolated mediastinal metastases from ovarian carcinoma are considered exceptional. Since such metastases are considered advanced stage disease, systemic therapy is the indicated therapeutic approach; however, some articles report that surgical excision is also feasible. Methods: We reviewed the English-language literature to detect cases of isolated mediastinal ovarian cancer metastases and present the management applied as well as their outcomes. Results: From 1998 to 2022, 15 such cases have been reported, with 4 of those cases being primary ovarian cancer presentation and 11 being ovarian cancer recurrence. The histology of the tumor was serious in all of the cases. Regarding the management of cancer, various methods were applied. In total, 11 of the patients underwent a surgical resection of the mediastinal metastasis, 2 received systemic therapy, 1 received a combination of palliative chemotherapy and radiation and the last patient was treated with laser debulking and radiotherapy. The mean reported follow-up was 11 months. Conclusions: Solitary mediastinal metastasis from ovarian cancer is very rare; physicians should pay close attention when routinely evaluating thoracic scans from patients with ovarian malignancy as well as individualizing the management in such patients, since surgical resection can also be performed. However, definitive conclusions cannot be drawn from the small number of case reports available. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is defined as an autoimmune inflammatory disease that affects the skin, the blood vessels and the muscles. It typically presents with erythema affecting mostly the eyes and the hands as well as proximal muscle weakness. It has been also correlated with various types of cancer, including ovarian cancer. A systematic PubMed and Scopus search was conducted. A total of 110 women were included in our review. The median age of the patients was 52.5 years (8–85). The most frequent histological type of malignancy was epithelial (87 cases, 79.1%) and in only one patient (0.9%) DM was co-existing with a cancer recurrence. A clinical diagnosis of DM or PM preceded the diagnosis of ovarian cancer in 69.1% (76/110), while paraneoplastic DM after the diagnosis of ovarian cancer was reported in 31% (34/110). Serum antibodies were present in 22.5% (25/110) and the median creatine kinase during first evaluation was 886 (56.6–16,596). Postoperative improvement of the symptoms was observed in 24.6% (27/110) while also 24.6% (27/110) needed post-treatment rheumatological management. Neoadjuvant chemotherapy or radiotherapy was necessary in 58.2% (64/110) and a cancer recurrence was identified in 28.2% (31/110), with a median follow up of 24.5 months (5–210). Finally, 52 (47.3%) deaths were reported in a median follow-up period of 16 months (0–210). It is crucial that DM patients should receive a thorough evaluation for ovarian cancer, among other malignancies, encompassing an abdominal CT or MRI scan and serum Ca-125 marker measurements. Treatment of ovarian cancer is usually accompanied by remission of DM symptoms in most of the cases.

Primary peritoneal serous carcinoma (PPSC) is a rare malignancy, the clinical characteristics of which resemble ovarian serous carcinoma. We present a rare case of PPSC detected by an abnormal cervical smear, the first one with an absence of ovarian tissue at the time of the initial diagnosis.A 59-year-old asymptomatic woman presented with glandular atypia on routine Papanicolaou smear. Endocervical and endometrial curettage showed an adenocarcinoma with focal squamous differentiation and uncertain further classification. The patient had a past surgical history of bilateral salpingoophorectomy due to endometriosis. Abdominal MRI depicted omental multinodularity, great amount of ascites and possible endometrial tumor. The patient underwent total hysterectomy, omentectomy and biopsies of implants on Douglass pouch. Surgical and histological findings were consistent with primary peritoneal serous carcinoma. Abnormal pap smear could rarely be suggestive of extrauterine malignancies, such as peritoneal cancer.

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual’s diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = −0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term.