Risk factors for Charcot foot development in individuals with diabetes mellitus.

AIMS/HYPOTHESIS: Charcot foot is a complication of diabetes mellitus that has potentially disastrous consequences. Although it was first described in 1868 and found to be associated with diabetes in 1936, there is still uncertainty about the risk factors affecting the development of the condition. Here, we aim to identify risk factors for Charcot foot in a nationwide cohort study. METHODS: A retrospective register-based cohort study was performed for the period 2001-2016, using nationwide registries. Individuals with diabetes and Charcot foot were identified and matched by diabetes type and with similar diabetes duration with individuals with diabetes but not Charcot foot. Logistic regression analyses were used to identify risk factors. RESULTS: A total of 3397 participants with diabetes mellitus and Charcot foot and 27,662 control participants with diabetes but without Charcot foot were included. HbA1c, duration of diabetes, micro- and macroalbuminuria, retinopathy and atherosclerosis (general and peripheral) were identified as risk factors for Charcot foot in participants with type 1 diabetes and participants with type 2 diabetes. CONCLUSIONS/INTERPRETATION: In the most extensive study on Charcot foot to date, we identified distinctive and common risk factors associated with the development of Charcot foot in individuals with type 1 diabetes and type 2 diabetes.

Cervical Twin Heterotopic Pregnancy: Overview of Ectopic Pregnancies and Scanning Detection Algorithm.

Background: Ectopic pregnancy is the leading cause of gestation-related deaths during the first trimester. Cervical twin heterotopic pregnancies, when ectopic, constitute a small and rare part of gynecological surgery. Case Presentation: A 30-year-old pregnant woman (gravida 3, para 2) presented with mild pain in the lower abdomen and traces of bleeding per vaginum for three days. Transvaginal ultrasonography revealed a balloon-shaped cervical canal with a visible gestational sac measuring 3.5 × 3.9 cm. A second gestational sac was seen in the uterine cavity. The measurements of the gestational sacs corresponded to 7 + 4 weeks' pregnancy. A decision for medical abortion with mifepristone and misoprostol was made. However, due to an incomplete abortion and continuous bleeding, a curettage was performed. Conclusions: Spontaneous heterotopic pregnancy with the ectopic pregnancy located in the cervix is an extremely rare clinical condition requiring urgent treatment in order to reduce maternal mortality and morbidity and preserve fertility.

Breast Cancer Apoptosis and the Therapeutic Role of Luteolin.

Breast cancer represents one of the three most common gynecological cancers, with each subtype having distinct risk profile and treatment strategies. Optimal therapy for each case depends not only on tumor subtype and cancer stage, but also on patient preferences. Thus, the final therapeutic choice seems complicated to be reached. In addition, frequent relapses and the aesthetic effects have led to the search for more effective and less invasive methods. Surgical interventions have become less complex and new hormonal and chemotherapeutic drugs are established, that promise great results, either combined to surgical treatment or used exclusively. Luteolin is a representative of natural flavonoid that has proven to modulate various signaling pathways involved in cancer development. Recent data demonstrate that luteolin induces apoptotic cell death via antioxidant activity, acting as an anticancer agent against various types of human malignancies including breast cancer. The aim of this review is to summarize latest data considering the therapeutic role of luteolin in breast cancer.

Ductoscopy Coupled to Duct Lavage and Duct Brushing in Pathologic Nipple Discharge: Our Experience.

PURPOSE: to present our experience in the management of pathological nipple discharge using the procedure D.DL.DB: "ductoscopy" (D) coupled to "duct lavage" (DL) plus "duct brushing" (DB) for etiologic diagnosis. Also to compare the diagnosis obtained with D.DL.DB to the final histology. MATERIAL AND METHOD: Eighty-five patients with organic unilateral nipple discharge were enrolled in two Breast Units. 82 of 85 patients were investigated successfully with D.DL.DB. Results:: The final histological results were: papilloma 46.3%, duct ectasia 36.5%, breast cancer 8.5%, precancer lesions 4.9%, and mixed benign lesions 3.8%. Pyramidectomy and radical ductectomy were performed in 76 and 6 cases respectively. In 80% of the cases, DLDB cytology results were identical to the final histology. (Kappa=0;69 CI=[0.56 -0.82]. The sensitivity of D.DL.DB versus pathology, for cancer or precancer lesions was 81.8% (CI=0.59 -1) and the specificity was 97.1% (CI=0.93 -1). Using Koch scale, the concordance between the two methods D.DL.DB and surgery was high and the sensitivity was in the upper range regarding the literature (58% to 90%). CONCLUSION: Our experience confirms the high value of D.DL.DB in the management of organic nipple discharge.

Primary Cervical Carcinosarcoma: Report of a Rare Case.

Background Carcinosarcomas are malignant mixed Müllerian tumors (MMMT), containing both epithelial and mesenchymal components. Carcinosarcomas of the uterine cervix comprise an extremely rare histopathological entity, with less than 150 cases reported in the literature to date. Materials and Methods A 79-year-old postmenopausal female patient was referred to our gynecological department due to a pelvic mass and vaginal bleeding. A cervical curettage was performed and the histological report revealed a malignant neoplasm with high cellularity consisting of two components; the first was a chondrosarcoma and the latter a adenocarcinoma. A diagnosis of MMMT was confirmed through immunohistochemical (IHC) staining. Neoadjuvant chemotherapy and radiotherapy were implemented, and a year later the patient underwent a radical hysterectomy and oncological pelvic lymph node dissection. She remains disease-free 12 months postoperatively. Conclusion Primary cervical carcinosarcomas are extremely rare tumors demonstrating a bipartite profile. Preoperative diagnosis with appropriate immunochemistry testing of this rare entity is crucial to decision making.

Mastitis and Risk of Breast Cancer: a Case Control-Retrospective Study and Mini-Review.

Objective: To investigate a possible association between mastitis and breast cancer risk in a cohort of Greek women. Material and methods:A series of 343 women who visited two breast clinics in Greece and delivered live neonates were studied in our case-control retrospective study. The case group comprised women with breast cancer and the control group women without breast cancer. All participants were subjected to a clinical examination with breast ultrasound and those aged over 40 years underwent digital bilateral mammography. Results:The χ2 (chi-square) test was the statistical tool used by us. We noted a statistically significant relationship between mastitis and risk for breast cancer (p=0.04). Moreover, the relative risk for breast cancer among patients with mastitis was RR: 2.069. Conclusion:Our study showed a relation between mastitis and breast cancer. Mastitis could be a potential risk factor. Further studies with larger number of patients are mandatory in order to confirm this possible relationship.

Breastfeeding and Breast Cancer Risk: Our Experience and Mini-review of the Literature.

Background: According to data from World Health Organization, breast cancer constitutes the second most common diagnosed malignancy after lung cancer and the second leading cause of death among women in 2020, worldwide. The protective role of breastfeeding in the emergence of breast malignancy has been mentioned in several studies, indicating the important part it can have in the effort of reducing breast cancer's incidence. Objective: To investigate a possible association between breastfeeding and breast cancer risk in Greek women. Methods: Totally, 391 women participated in our case-control retrospective study. In the case group included 238 women with breast cancer, while in control group 153 women without breast cancer who were enrolled in two breast clinics in Greece. All women were examined clinically and with breast ultrasound, while those older than 40 years old also with bilateral digital mammography. Results: The x2 (chi-square) test found a statistically significant reverse correlation between breast cancer and breastfeeding ⩾12 months (cumulative) (p = 0.001). It was observed that the percentages of patients who breastfed ⩾12 months were lower than those of healthy women. Conclusion: Breastfeeding and particularly the cumulative period of ⩾12 months is related to the maximum of the protection from breast cancer.

A Potential Pathogenic Link Between Cancer of Female Reproductive System and Infertile Women Treated With Assisted Reproduction Techniques.

Prevention and treatment of infertility remains a priority for developed countries where a large proportion of women undergo in vitro fertilization (IVF) after ovarian stimulation. Latest data suggest that, in the USA alone, almost eight million women of fertile age will have sought medical advice for fertility problems by 2025. However, over the last years, attention has been increasingly focused, and questions have risen, on the long-term health effects in women who underwent assisted reproductive technologies (ARTs). Since the emergence of ART, reports highlight a possible connection of ovarian stimulation and several types of gynaecological cancer, including ovarian, endometrial and cervical types, but due to limited scientific evidence, such a speculation is still under investigation. The objective of this review is to summarize the latest data of ovarian hyperstimulation and IVF, associated with the risk of gynecological tract cancer development.

Risk Factors of Synchronous Breast and Thyroid Cancer: a Controlled Multicenter Study and Review of the Literature.

BACKGROUND: Breast cancer (BC) is one of the most common cancers diagnosed in women in the United States. Thyroid cancer (TC) is also one of the fastest increasing cancer types in the United States, with most cases being papillary thyroid carcinomas. OBJECTIVE: To identify possible risk factors for the synchronous or metachronous co-occurrence of breast and thyroid cancers. METHODS: We carried out a study, which consisted of data from four gynecological clinics: two in Greece (Athens, Alexandroupolis, Ioannina) and one in Germany, collected from June 2017 to June 2020. The patients were divided into two groups: the first group consisted of 58 patients with breast cancer and a personal history of thyroid cancer. The second group (control group) included 50 patients with the same characteristics as to age, parity, type of pregnancy, treatment for sterility, polycystic ovaries, regularity of the menstrual cycle, breast density, BMI, family history of cancer, blood group rhesus and histological results of breast cancer. The data we collected were analyzed using version 20 of the SPSS statistical package. The Chi-square test was used for statistical analysis and a p-value<0.005 was considered statistically significant. RESULTS: The only factors that seem to be related with the association of breast and thyroid cancer were: history of abortion and multiparity. CONCLUSION: In our study there is a higher chance of developing breast cancer after diagnosing thyroid cancer and vice versa. More than genetic mutations, a possible hormonal pathway of these two malignancies is possible. The hormonal change in women who had many children or abortions could be a risk factor to develop both cancers. More studies are necessary to confirm our findings.

Neonatal Birth Weight of the Woman as a Risk Factor for Breast Cancer in her Life: a Case-Control Bicentric Study.

BACKGROUND: It is a global fact that the birth weight is increasing during the years around the world and for this reason it is very important to be examined as a potential risk factor for breast cancer. According to data from World Health Organization, breast cancer is the second most frequent malignancy across the world, after lung cancer, in Europe including Greece in incidence and mortality for women between the ages 0-85 years old. OBJECTIVE: The aim of this study was to investigate a possible association between neonatal birth weight of the women and breast cancer risk in Greek women. Although that many studies concluded that birth weight is positively related with breast cancer reinforcing the theory that breast cancer may originate in utero, some studies found no association. Moreover, the results from previous studies are inconsistent maybe due to several factors such as the study design and the number of cases. METHODS: This study was a case-control retrospective bicentric study. The case group included 238 women with breast cancer, while the control group included 153 women without breast cancer who consulted in two breast clinics in Greece. In all women, a clinical examination and breast ultrasound were achieved. Moreover, digital bilateral mammography was performed in patients older than 40 years. RESULTS: According to Fisher's exact analysis, there is a statistically significant relationship between the higher women's neonatal birth weight and the risk for breast cancer (p<0.001). More specifically in the group of women with breast cancer, 61% of them had more than 3500 grams birth weight, in contrast with 7.8 % in the control group. In our cohort, women who had birth weight more than 3500 grams are more likely to develop breast cancer in their life. CONCLUSION: Our study trend to show that the increased neonatal birth weight may influence future risk of breast cancer. However, further studies with larger number of participants are needed in order to clarify the role of birth weight as a complementary risk factor of breast cancer.

Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review.

Cancer is a medical condition which has a molecular basis. Proto-oncogenes are the first regulatory factors of this biological process. They act in transmitting signals, resulting as growth factors. Modifications of these genes, called oncogenes, lead to the appearance of cancer cells. The activation process leading to proto-oncogenes are chromosomal translocation, point mutation, and gene amplification. Concerning the clonal theory of oncogenesis, it is believed that a tumor starts from a cell. Furthermore, there is close association between tumor development and inhibition of apoptosis or programmed cell death, providing cell immortality. Angiogenesis and angiogenic factors found to be expressed in tumors and may play a key role in tumor formation and development. Tumor-suppressor genes block the growth of cancer and contribute to the normal development of cells. This article highlights the evidence that neoplasms develop as the after-effect of the increase of acquired and physical genetic variations in proto-oncogenes and tumor-suppressor genes; these form a target group in the cells of neoplasms. Tumor formation and development are characterized by individual processes, working synergistically, and an understanding of each individual process may provide a better basis for further anticancer research.

Primary Malignant Melanoma of the Cervix: A Case Report and a Review of the Literature.

BACKGROUND: Gynecologic melanomas are extremely rare malignancies, and primary malignant melanoma of the cervix (PMMC) is the rarest among them all, with less than 100 cases reported so far. Although some conditions have been correlated with the pathogenesis of this entity, no specific risk factor has been yet identified, with vaginal bleeding being the most common symptoms. The diagnosis is based on physical examination with speculum assessment and cytologic and histopathologic findings accompanied with immunohistochemical staining of lesion's biopsies. Case Presentation. We report a case of PMMC in a 34-year-old para-2 patient, among the youngest cases of PMMC reported, that presented to our clinic for routine examination. Gynecologic examination demonstrated a dark, heavily fully pigmented cervical growth completely covering the entire external cervical os. Biopsy obtained and showed malignant melanoma. She underwent radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The pathological diagnosis was FIGO stage IB1 PMMC. Despite 2 courses of anti-PD-1 antibody (Nivolumab) treatment, the patient passed away 13 months after diagnosis (12 months after surgery). CONCLUSIONS: Early diagnosis and subsequently early treatment are of high importance regarding patients' prognosis and survival. No standardized protocols or treatment guidelines specific for this rare cancer have been issued; thus, clinicians are called to assess each case individually. Current treatment options are based on surgical excision mostly with radical hysterectomy, but in advanced or recurrent state of the disease, other treatment modalities, such as chemotherapy, radiotherapy, and immunotherapy, can be employed. Prognosis for these patients is very poor, and survival rate remains extremely low, with the median OS reported being less than 2 years. Reporting and publishing of such cases are both of paramount importance for the better understanding of this uncommon cervical malignancy, and further biological and clinical investigations are required for more suitable and effective therapies to be determined. A new staging system, specific to PMMC, could be of great use for the better correlation of the disease's stage and prognosis of these patients.

A Rare Case of Massive Hematometra with a Tubo-ovarian Abscess in a 16-year-old Female.

Imperforate hymen is a congenital defect of the lower genital tract and specifically the vagina. The examination of a neonatal can be quite helpful to avoid a multitude of complications in puberty like hematocolpos and tubo-ovarian abscess. We present the case of a 16-year-old who presented to the emergency department with fever (37.9° C), which was progressive the last two days, swollen abdomen, and pain in the lower abdomen. She also had a one-year history of cyclic abdominal pain. The patient had primary amenorrhea, the secondary sexual characteristics were normal for her age (Tanner III), and there was no family history of primary amenorrhea. The physical and ultrasound examination revealed an imperforate and bulging vaginal membrane and a multilocular adnexal mass, respectively. Every doctor should suspect this medical condition when there is a triad of symptoms like cyclic lower abdominal pain, primary amenorrhea, and swollen abdomen. Early diagnosis of an imperforate hymen can prevent serious complications for young patients.

The Role of ARID1A in Endometrial Cancer and the Molecular Pathways Associated With Pathogenesis and Cancer Progression.

AT-rich interaction domain 1A gene (ARID1A) encodes for a subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, a chromatin remodeling complex, and it has been implicated in the pathogenesis of various cancer types. In this review, we discuss how ARID1A is linked to endometrial cancer and what molecular pathways are affected by mutation or inhibition of ARID1A. We also discuss the potential use of ARID1A not only as a prognostic biomarker, but also as a target for therapeutic interventions.

Comparative Evaluation of Arabin Pessary and Cervical Cerclage for the Prevention of Preterm Labor in Asymptomatic Women with High Risk Factors.

OBJECTIVE: Preterm labor is one of the most significant obstetric problems associated with high rate of actual and long-term perinatal complications. Despite the creation of scoring systems, uterine activity monitoring, cervical ultrasound and several biochemical markers, the prediction and prevention of preterm labor is still a matter of concern. The aim of this study was to examine cervical findings for the prediction and the comparative use of Arabin pessary or cerclage for the prevention of preterm birth in asymptomatic women with high risk factors for preterm labor. MATERIAL AND METHODS: The study group was composed of singleton pregnancies (spontaneously conceived) with high risk factors for preterm labor. Cervical length, dilatation of the internal cervical os and funneling, were estimated with transvaginal ultrasound during the first and the second trimesters of pregnancy. RESULTS: Cervical funneling, during the second trimester of pregnancy, was the most significant factor for the prediction of preterm labor. The use of Arabin cervical pessary was found to be more effective than cerclage in the prolongation of pregnancy. CONCLUSION: In women at risk for preterm labor, the detection of cervical funneling in the second trimester of pregnancy may help to predict preterm labor and to apply the appropriate treatment for its prevention. Although the use of cervical pessary was found to be more effective than cerclage, more studies are needed to classify the effectiveness of different methods for such prevention.