Challenges in Diagnosis and Treatment of a Cervical Carcinoma Complicated by Genital Prolapse.

Cervical squamous cell carcinoma of the uterus associated with pelvic organ prolapse is very rare and usually occurs in elderly women. We hereby present an 81-year-old postmenopausal woman presented to the outpatient department with an ulcerated irreducible uterine procidentia. The prolapse was reduced under general anesthesia and biopsy of the lesions confirmed a cervical squamous cell carcinoma. Pretreatment clinical staging revealed a 16 cm enlarged uterus and mild to moderate unilateral hydroureteronephrosis, secondary to periureteric infiltration, clinical stage IIIB. The patient was disqualified from surgery, and palliative chemotherapy plus radiotherapy was recommended. Patient's general condition was rapidly deteriorated, and three months after the diagnosis, the patient passed away. Therapeutic management of cervical cancer associated with uterovaginal prolapse is not well established. Hence, this article presents the clinical concerns that arise in such rare and neglected cases.

Spontaneous Intraoperative Rupture of a Large Interstitial Pregnancy: Laparoscopic Management.

We present a case of a large interstitial pregnancy which was intraoperatively ruptured, but was eventually laparoscopically treated. The patient experienced 9 weeks of amenorrhea, and a right cornual pregnancy measuring 6 cm was diagnosed. The patient consented on having a minimal surgical treatment, and a laparoscopic right cornuotomy was decided. During surgery, and prior to any manipulation to the uterus, there was a spontaneous rupture of the ectopic which resulted in excessive bleeding. Temporal pressure at the bleeding site and ligation of the superior branches of the right uterine artery allowed for a careful dissection of the right uterine cornua and achieved hemostasis. The surgery proceeded uneventfully thereafter. Although surgical intervention in such cases entails a high risk of hemorrhage, successful completion of the laparoscopy lies on the meticulous preoperative planning and the controlled precise surgical steps during the procedure.

Prenatal sonographic diagnosis of biliary tract malformations.

Congenital anomalies of the biliary tract include a variety of pathologic conditions, such as biliary atresia, choledochal cysts, gallbladder agenesis, congenital cholelithiasis, and gallbladder duplication. Although most of these malformations are rare and benign conditions, they may occasionally represent a major threat to extrauterine life. Visualization of a normal-sized gallbladder should be a mandatory component of the second-trimester anomaly ultrasound scan. Advances in prenatal sonography enable the detection of biliary tract congenital malformations. In this review, we discuss the detection rates, sonographic features, and prognosis of the most frequently prenatally diagnosed biliary tract malformations.

Gastrointestinal and Urinary Tract Endometriosis: A Review on the Commonest Locations of Extrapelvic Endometriosis.

Extrapelvic endometriosis is a rare entity that presents serious challenges to researchers and clinicians. Endometriotic lesions have been reported in every part of the female human body and in some instances in males. Organs that are close to the uterus are more often affected than distant locations. Extrapelvic endometriosis affects a slightly older population of women than pelvic endometriosis. This might lead to the assumption that it takes several years for pelvic endometriosis to "metastasize" outside the pelvis. All current theories of the pathophysiology of endometriosis apply to some extent to the different types of extrapelvic endometriosis. The gastrointestinal tract is the most common location of extrapelvic endometriosis with the urinary system being the second one. However, since sigmoid colon, rectum, and bladder are pelvic organs, extragenital pelvic endometriosis may be a more suitable definition for endometriotic implants related to these organs than extrapelvic endometriosis. The sigmoid colon is the most commonly involved, followed by the rectum, ileum, appendix, and caecum. Most lesions are confined in the serosal layer; however, deeper lesion can alter bowel function and cause symptoms. Bladder and ureteral involvement are the most common sites concerning the urinary system. Unfortunately, ureteral endometriosis is often asymptomatic leading to silent obstructive uropathy and renal failure. Surgical excision of the endometriotic tissue is the ideal treatment for all types of extrapelvic endometriosis. Adjunctive treatment might be useful in selected cases.

Subcutaneous emphysema to the head and neck: an unlikely traumatic origin.

Subcutaneous emphysema to the neck represents a rare entity mainly derived from iatrogenic and traumatic origin. We report a case of a subcutaneous emphysema resulted from an intraoral injury aiming to emphasise the significance of precise medical history to identify an unlikely mechanism. A 40-year-old female patient was presented with subcutaneous emphysema extending from the region underneath the left eye up to the submandibular area of the neck. The patient complained of painful, swollen neck. The patient mentioned that the symptoms began after an intraoral injury accidentally caused by the use of a high-pressure water jet device meant for car wash. The patient was managed conservatively and was discharged after 2 days. This case highlights the urgency for clinical suspicion for unlikely mechanisms. Moreover, the manufacturer companies should alert and give official warning for the contingency of injury due to incorrect or careless usage.

Placental expression of PAPPA, PAPPA-2 and PLAC-1 in pregnacies is associated with FGR.

Fetal growth restriction (FGR) is a gynecological disorder of varying etiology. In the present study, an expression analysis of pregnancy-associated plasma protein A (PAPPA), pregnancy-associated plasma protein A2 (PAPPA2) and placenta-specific-1 (PLAC-1) was conducted in pregnancies with FGR and control pregnancies. Placental tissues were collected from pregnancies with FGR (n=16) and control pregnancies (n=16) and the expression of the genes of interest was examined by qPCR. The mean expression levels of PAPPA and PAPPA2 were significantly lower (P<0.001) in placental tissues from FGR pregnancies compared with tissues from healthy subjects, whereas the opposite pattern was observed for PLAC-1 (P<0.001). PAPPA and PLAC-1 expression in FGR and control subjects correlated with birth weight (P<0.001). The findings suggest a possible pathophysiological link between the development of FGR and the expression of PAPPA, PAPPA2 and PLAC-1.

Macroscopic Hematuria due to Placenta Percreta: Report of Two Cases and Short Review.

Herein we present two cases of pregnant women with placenta percreta and severe hematuria during the 24th and 35th weeks of pregnancy, respectively. A timely sonographic diagnosis was feasible in the first case and cesarean section was performed during the 29th week. During the operation, the placenta was invading the bladder wall and concomitant hysterectomy with cystotomy and bladder wall reconstruction was performed. The second case presented in our emergency department with vaginal bleeding during the 35th weeks of pregnancy. She underwent an emergency cesarean section with uterine preservation, cystotomy, and bladder reconstruction.

Laparoscopic excision of an inflammatory myofibroblastic tumour of the bladder disguised as deep infiltrating endometriosis.

Inflammatory myofibroblastic tumour (IMT) of the bladder is a rare tumour of indeterminate malignant potential with myofibroblastic differentiation, with a generally benign but rarely aggressive behaviour. Vesical IMT is usually treated by transurethral resection or partial cystectomy. Herein we describe a case of a woman who underwent laparoscopic excision of an IMT of the bladder, initially diagnosed as deep infiltrating endometriosis.

DNA methylation in endometriosis (Review).

Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis.

Laparoscopic treatment of a large uterine cystic adenomyosis in a young patient.

We describe a rare case of a young woman with a large cystic adenomyotic lesion that was treated laparoscopically. The patient presented with severe dysmenorrhoea refractory to common analgaesics. She was initially diagnosed with right-sided ovarian endometrioma. MRI revealed a cystic lesion of 4 cm attached to the right uterine wall. Under laparoscopic vision, the uterine lesion was identified on the right portion of the uterine fundus close to the round ligament. Monopolar diathermy was used to dissect the lesion. When the incision reached the cystic cavity, dark-brown content flowed from the cyst. After resection was complete, the surgical wound was closed with two-layer interrupted sutures. The patient made a good recovery and was discharged the following day. Since patients with cystic adenomyosis are young, a minimally invasive procedure such as laparoscopic excision is considered optimal. The exact topography of the lesion is crucial in determining the site of the incision.

A rapidly growing vulvar condyloma acuminatum in a young patient.

A young woman presented to the outpatient gynaecology clinic with a rapidly growing bulky tumour located at the external genitalia, which she first noticed 10 days prior to her visit. Examination revealed a 6 × 3 cm cauliflower-like mass located on the left genitofemoral fold. The initial biopsy had several features suggestive of a human papilloma virus (HPV) infection. A broad excision of the mass was subsequently performed. The biopsy confirmed the presence of a large condyloma acuminatum. Condyloma acuminatum is a slow-growing benign exophytic tumour that is associated with HPV infection. In cases where the tumour has aggressive features, as in our patient, the differential diagnosis has to include carcinoma or Buschke-Löwenstein tumour. The initial biopsy of the tumour in our patient, however, excluded malignancy.

DNA methylation profiles in ovarian cancer: implication in diagnosis and therapy (Review).

Genetic alterations alone cannot account for the complexity of ovarian cancer. The potential reversibility of epigenetic mechanisms makes them attractive candidates for the prevention and/or treatment of ovarian carcinoma. Detection of the epigenetic signature of each cancer cell may be useful in the identification of candidate biomarkers for disease detection, classification and monitoring and may also facilitate personalized cancer treatment. In ovarian cancer, in addition to other non­gynaecological cancers, two opposite epigenetic phenomena occur. The first involves an overall global decrease in DNA methylation of heterochromatin leading to demethylation of several oncogenes, while the second involves specific CpG island hypermethylation associated with the promoters of tumor suppressor genes. Early studies focused on the methylation patterns of single genes associated with tumorigenesis. However, newer genome-wide methods have identified a group of genes whose regulation is altered by DNA methylation during ovarian cancer progression.

Reduced ANXA5 mRNA and protein expression in pregnancies complicated by preeclampsia.

INTRODUCTION: The placental anticoagulant protein Annexin A5 (ANXA5) is a multifunctional protein that is highly expressed on the apical surfaces of syncytiotrophoblasts, and plays an important role in haemostatic regulations, maintaining blood fluidity of the placenta. The aim of this study was to investigate the expression of ANXA5 in pregnancies complicated by preeclampsia (PE). MATERIALS AND METHODS: Placental tissue samples were collected from 23 pregnancies with PE and 34 normal pregnancies. ANXA5 mRNA levels were measured by quantitative Real-Time PCR (qPCR), while ANXA5 protein expression was measured by Western Blot (WB) and immunohistochemistry. RESULTS: ANXA5 mRNA expression in PE samples was lower than 1% of its expression in normal samples (mean ± SD: 0.002 ± 0.004 vs. 0.55 ± 0.38, p < 0.001), while ANXA5 protein levels in PE samples were approximately at 65% of the average normal expression (mean ± SD: 0.53 ± 0.30 vs. 0.81 ± 0.25, p=0.001). Immunohistochemical analysis also verified the above results, since PE placentas tended to have low labelling indexes (LIs), in contrast to controls which demonstrated high LIs (p=0.020). Statistical analysis of the WB data revealed that ANXA5 protein expression was increased in PE smokers vs. PE non-smokers (mean ± SD: 0.64 ± 0.23 vs. 0.41 ± 0.33, p=0.027). CONCLUSIONS: These results suggest that ANXA5 downregulation could be part of the pathophysiology of PE and the possible impairment in coagulation processes, which are seen in pregnancies that demonstrate PE. Further studies may investigate whether ANXA5 could be used as a biomarker for the early detection of PE and for the prediction of its severity.

Long-term quality of life and patient satisfaction following anterior vaginal mesh repair for cystocele.

PURPOSE: The aim of this study was to assess the relationship between long term quality of life (QoL), patient satisfaction, and Pelvic Organ Prolapse Quantification (POPQ) scores following anterior vaginal repair with mesh. METHODS: This cross-sectional study included 127 patients who underwent anterior pelvic floor repair with mesh and were assessed 1.03-2.69 years post surgery. One hundred and four women completed the King's Health Questionnaire (KHQ), the Sheffield Prolapse Symptoms Questionnaire, the EurolQoL EQ-5D, and the Patient Satisfaction Index. POPQ scores were recorded for up to 1 year. RESULTS: Patients reported good current QoL and high patient satisfaction. POPQ Aa and Ba scores showed significant improvements from a pre-surgery median of +1 to a median of -3 at 12-month follow-up (P < .001). Patient satisfaction was inversely correlated with Aa scores at 12 months (r(s) = -.360, n = 49, P < .011). There were high QoL scores at an average 2 years after anterior compartment mesh repair. CONCLUSIONS: QoL outcomes were good. There was a significant relationship between Aa scores and patient satisfaction, suggesting that this outcome is a key to patient satisfaction.

DNA methylation in the human placenta and fetal growth (review).

Throughout in utero development, the placenta plays a key role in controlling growth and development. The placenta acts not only as a gatekeeper of nutrient and waste exchange between mother and developing fetus, but also as a regulator of the intrauterine environment. Its functions can be influenced by the environment encountered throughout pregnancy, thereby altering the appropriate genetic programming needed to allow for appropriate fetal growth. Epigenetic alterations related to environmental exposures have been linked to aberrant fetal growth. DNA methylation, which is the best known DNA epigenetic modification, may provide an attractive mechanism linking environmental cues to placental pathology, with consequences for fetal growth and adult life. Alteration of the methylation patterns of genes expressed in the placenta has recently been found to modify gene expression and subsequently impair function of the placenta. Although there is strong evidence to demonstrate that the environment can affect the pattern of DNA methylation of the placenta during fetal development, a direct association between environmental conditions, methylation alterations and gene expression is difficult to confirm. DNA methylation in the placenta has mainly been investigated in the context of imprinted and non-imprinted genes transcription. Several environmental factors have also been assessed in regard to their association with changes to the epigenetic motives of embryonic and extraembryonic tissues and their impact on pregnancy outcome. In this review, we briefly present the available evidence regarding the role of DNA methylation patterns of the placenta on aberrant fetal growth.

Loss of imprinting and aberrant methylation of IGF2 in placentas from pregnancies complicated with fetal growth restriction.

The objective of this study was to investigate the hypothesis that the altered epigenetic mechanisms that regulate IGF2 imprinting in placentas from fetal growth restricted (FGR) pregnancies affect IGF2 expression leading to impaired fetal growth. We investigated gene transcription, genotyping and the methylation patterns of IGF2 from 31 and 17 placentas from FGR-complicated and normal pregnancies, respectively. A statistically significant decrease in IGF2 mRNA levels was observed in the placentas from the FGR pregnancies. Loss of imprinting (LOI) was only detected in the abnormal placentas. The evaluation of the percentage of the methylated reference (PMR) of two different potentially differentially methylated regions (DMR) demonstrated significant PMR values in both sites for the normal and FGR pregnancies with no significant differences. Our results suggest the involvement of the IGF2 imprinted gene in placental function and fetal growth and the possible association of epigenetic alterations with the pathophysiology of fetal growth restriction.

Decreased placental expression of hPGH, IGF-I and IGFBP-1 in pregnancies complicated by fetal growth restriction.

OBJECTIVE: The human Placental Growth Hormone (hPGH) and the Insulin-like Growth Factor (IGF) system are implicated in fetal development. This study aimed to evaluate the expression of hPGH, IGF-I, IGFBP-1 and IGFBP-3 genes in placentas from pregnancies complicated by fetal growth restriction (FGR). DESIGN: The study group was comprised of term placentas from 47 FGR-complicated pregnancies of no recognizable cause. Thirty-seven placentas from normal pregnancies with appropriate for gestational age birth weight were used as controls. The expression status of the genes was evaluated by quantitative real-time PCR. RESULTS: hPGH, IGF-I and IGFBP-1 exhibited significantly lower expression compared to the controls (p=0.003, p=0.049 and p=0.001, respectively). Numerically, lower IGFBP-3 expression was also demonstrated in the FGR-affected group, without however reaching statistical significance (p=0.129). Significant co-expression patterns were detected among the study genes in both the FGR and normal pregnancies. CONCLUSION: Decreased placental expression levels of hPGH, IGF-I and IGFBP-1 were demonstrated in pregnancies with FGR. Whether these alterations are a causative factor of FGR or accompany other pathogenetic mechanisms requires further investigation.

Urethral diverticulum mimicking anterior vaginal wall prolapse: case report.

Unfamiliar cystic formations may develop in the anterior vaginal wall. In view of the close proximity of the anterior vagina to the urethra and bladder, it is important that management of such masses is carefully planned after detailed examination and investigation. Herein, we present the case of an unusual painful swelling in the anterior vaginal wall that was first diagnosed as vaginal wall prolapse. Despite thorough preoperative investigations, the origin of the mass as a urethral diverticulum was confirmed only at pathologic analysis.