Metaproteomic analysis from cervical biopsies and cytologies identifies proteinaceous biomarkers representing both human and microbial species.

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity.

Antiphospholipid syndrome in cardiovascular disease and cancer.

Antiphospholipid syndrome is an autoimmune disorder which is characterized by the presence of heterogeneous antiphospholipid antibodies. There is an evidence on antiphospholipid (aPL) antibodies related to thromboembolic events in cancer patients. In fact, the thrombotic complications in patients with malignancy occur at a rather high frequency, compared to other risk factors. In parallel with standard therapies available, there is need of case-by-case monitoring of each patient and the introduction of new therapies and need for more clinical trials which will address many questions for the optimal management of patients. This paper presents a basic review of the literature on the aPL antibodies associated with cardiovascular disease and cancer, as well as its complications, which are reported so far in the bibliography.

Surgical management of abdominal wall sheath and rectus abdominis muscle endometriosis: a case report and literature review.

Introduction: Endometriosis, defined as the presence of endometrial glands and stroma outside the uterine cavity, mainly affects the pelvic viscera and peritoneum. Endometriosis can also occur at sites of surgical incisions on the abdominal wall, mainly in women with a history of cesarean section (CS). The incidence of abdominal wall endometriosis after CS reaches 1%. Clinical suspicion, along with imaging, plays a crucial role in diagnosis. The preferred treatment involves extensive surgical excision with clear margins, ensuring a definitive diagnosis through histopathology examination. Case presentation: This case report is of a 44-year-old woman with a history of two CS procedures who developed pain and pigmentation at the incisional site one year after the last CS. Thirteen years after the surgical excision of an abdominal wall endometriosis (AWE) mass, followed by hormone therapy, she presented in our hospital with worsening pain for further management. Pelvic MRI findings were consistent with AWE. During surgery, the abdominal wall endometriosis foci were removed, and the defect in the aponeurosis was repaired using a dual-sided mesh in a tension-free procedure. Conclusion: Although AWE is a rare condition, we foresee an increase in cases because of the ever-increasing CS rates and the important association between AWE and CS. Healthcare practitioners should remain vigilant for this condition in women of reproductive age who exhibit cyclic pain, a palpable mass in the abdomen, and a background of previous uterine surgeries.

Laparoscopic Management of Cornual Ectopic Pregnancy: A Step-by-step Approach.

Interstitial and cornual pregnancies are dangerous, yet rare, forms of ectopic pregnancy, accounting for 2%-4% of all ectopic pregnancies. A 38-year-old female, para 1, gravida 3 had undergone another in vitro fertilisation (IVF) cycle (a salpingectomy performed elsewhere for treating a hydrosalpinx before a previous IVF attempt). Duration of pregnancy is 6 weeks and 5 days, a transvaginal ultrasound revealed an embryo with a positive foetal heartbeat, located in the left cornuum. As no conservative treatment option could be followed, we proceeded with laparoscopic removal of ectopic pregnancy through cornual resection. Since a specific surgical methodology has not yet been established, presenting more step-by-step surgical approaches that can be used in clinical practice is of high importance. We present a step-by-step surgical approach that we have implemented in cases of cornual pregnancy in our department.

Conjoined Twins Complicating a Dichorionic Triplet Pregnancy after Intracytoplasmic Sperm Injection: A Case Report and Review of the Literature.

Conjoined twins represent a rare type of monoamniotic twins. Ultrasound assessment during the first trimester can facilitate the diagnosis, however further assessment by colour Doppler studies, 3D imaging, fetal echocardiography and fetal magnetic resonance imaging (MRI) is usually required in order to determine the specific fetal abnormalities and to guide appropriate pregnancy management. This case report presents a rare case of conjoined twins complicating a dichorionic-diamniotic triplet pregnancy, achieved after intracytoplasmic sperm injection (ICSI) and blastocyst transfer. A 44-year-old woman was referred for chorionicity determination to our Fetal Medicine Centre due to suspicion of conjoined twins in a triplet pregnancy. Ultrasound assessment at 11 weeks demonstrated a dichorionic triplet pregnancy which was also complicated by a rare type of conjoined twins (thoracoomphalopagus) and after a successful embryo reduction a neonate of 2200 g was delivered by caesarean section at term. The accurate diagnosis and early detection of conjoined twins by a fetal medicine specialist is crucial, especially as far as multiple pregnancies with three or more fetuses are concerned.

Current Approaches to the Management of Patients with Endometrial Cancer.

The incidence of endometrial cancer (EC) is rising and healthcare professionals need to be informed about the latest data on the constant developments in the field of its management. With particular interest in the classification and management of EC, we surveyed current literature, national and international data, and guidelines, as well as the latest studies to present the most recent data regarding the management of EC. It became evident that despite the consensus on low-risk EC, there are still controversies surrounding the management of high-risk EC, especially regarding the role of sentinel lymph node biopsy (SLNB). Our aim is to present the old and new perspectives in the management of EC, the different available surgical routes, the possible desire for fertility preservation, the role of adjuvant therapies and the focus on the advantages and the limitations of the implementation of SLNB in therapeutic strategies. It became evident throughout our search and based on literature data that minimally invasive surgery (MIS) leads to satisfying outcomes, thus becoming gradually the preferred route of surgery, while SLNB could provide essential information and guidance about the overall management needed in cases of both low-risk and high-risk EC.

Familial Aggregation of a Novel Missense Variant of COL2A1 Gene Associated with Short Extremities: Case Report and Review of the Literature.

We present two cases of family members (first cousins) with short extremities caused by a novel variant of COL2A1 gene (NM_001844.5). Case 1 description: A 29-year-old woman presented in her first pregnancy for a second trimester anomaly scan at 23 weeks of gestation. Fetal long bones were measured below the third centile for gestational age. Follow-up scans revealed fetal long bone growth deceleration. Initial genetic work-up was negative and the rest of the maternal follow-up was unremarkable. A male baby weighing 3180 g was delivered at 39 weeks and 4 days of gestation. Case 2 description: A 33-year-old pregnant woman presented for a routine second trimester anomaly scan at 20 weeks and 4 days of gestation. All fetal measurements were appropriate for the gestational age. The routine growth scan performed at 32 weeks showed fetal long bone measurements below the third centile for gestational age, while the follow-up growth scan at 36 weeks and 4 days of gestation revealed consistent, below the third centile, fetal long bone growth. Given that the fetuses of these two cases were related (first cousins), whole exome sequencing (WES) was performed on Case 2. WES revealed a novel heterozygous missense variant c.1132G>A (p. Gly378Ser) of COL2A1 gene (NM_001844.5). Subsequently, targeted genetic sequencing for the variant was performed on Case 1 and the same novel variant was found. Targeted sequencing revealed the same variant in the mother of Case 1 and the father of Case 2 (siblings). A female baby weighing 3200 g was delivered at 40 weeks and 4 days of gestation.

Ovarian Tissue Cryopreservation in Children and Adolescents.

Cancer during childhood and adolescence remains a major public health issue, affecting a significant portion of this age group. Although newer anti-cancer treatments have improved survival rates, this comes at a cost in terms of gonadotoxic effects. As a result, the preservation of fertility is important. Ovarian tissue cryopreservation, one of the newest methods, has some advantages, especially for prepubertal patients: no need for ovarian stimulation, thus, no further risk for estrogen-sensitive cancer types, and preservation of more and better-quality primordial follicles of the ovarian cortex. The most frequent indications include treatment with alkylating agents, ovarian-focused radiotherapy, leukemias, lymphomas, brain and neurological tumors, as well as Turner syndrome and benign hemoglobinopathies. An expected survival exceeding 5 years, the absence of systematic disease and an overall risk of premature ovarian insufficiency over 50% are among the criteria that need to be fulfilled in order for a patient to undertake this method. Orthotopic transplantation is more frequently used, since it can allow both live birth and the recovery of endocrine function. Reimplantation of malignant cells is always a major risk and should always be taken into consideration. Histological analysis, as well as immunohistochemical and molecular methods, are needed in order to improve the search for malignant cells before transplantation. Ovarian tissue cryopreservation appears to be a method with specific benefits, indications and risks which can be an important tool in terms of preserving fertility in younger women.

The impact of Mayer-Rokitansky-Küster-Hauser Syndrome on Psychology, Quality of Life, and Sexual Life of Patients: A Systematic Review.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital syndrome characterized by uterovaginal agenesis. Most patients are diagnosed during adolescence, when body image and sexual identity are shaped. Our main objective was to investigate how MRKH syndrome affects psychology, quality of life (QoL), and the sexual life of patients compared with non-affected individuals. METHODS: Original peer-reviewed research papers examining psychological outcomes, QoL, and sexual function of MRKH patients were searched in PubMed. Titles, abstracts, and full text from potentially eligible records were reviewed by two independent reviewers. Case reports and papers published not in English were excluded. RESULTS: Our search identified 63 records, of which 20 were included: 10 examined psychological and psychosocial outcomes, 14 examined sexual function outcomes, and 6 examined QoL outcomes. Results may be affected by selection bias and confounding due to differences between MRKH patients and controls. CONCLUSIONS: MRKH could be associated with a higher prevalence of anxiety and depression symptoms and social insecurity compared with women of a similar age without the condition. MRKH could also be associated with greater pain and discomfort during sexual intercourse and limitations in arousal, lubrication, and orgasm. MRKH patients more commonly experience impairment of mental-health-related QoL, but physical-health-related QoL is not affected.

Preeclampsia and Cerebral Palsy in Offspring.

The aim of this systematic review and meta-analysis is to examine the association between exposure to preeclampsia during pregnancy and the occurrence of cerebral palsy in offspring. For this reason, the authors searched PubMed/Medline, EMBASE, and Google Scholar databases (end-of-search: 22 November 2021) and identified the most relevant studies. Then, a meta-analysis of all the eligible studies was performed. Subgroup and meta-regression analyses by study design, degree of adjustment, and geographical region were also conducted. A total of 10 studies were finally included, and no statistical significance was noted in the association between preeclampsia and cerebral palsy (pooled OR = 1.16, 95% CI: 0.77-1.74). The subgroup of studies that provided adjusted odds ratios for any variable except for gestational age showed a statistically significant association (pooled OR = 1.62, 95% CI: 1.36-1.93), whereas the association dissipated in studies also adjusting for gestational age (pooled OR = 1.63, 95% CI: 0.48-5.50). In conclusion, it seems that preeclampsia is not associated with cerebral palsy independently of gestational age; however, further research is needed to shed light on this topic.

Common Malignancies During Pregnancy: A Comprehensive Review.

Malignant disease complicates pregnancy in up to 1 per 1,000-2,000 cases. Pregnancy itself does not constitute a predisposing factor for malignancy. Management and treatment of patients suffering from a malignancy during pregnancy still represents a challenge in everyday clinical practice. Recent advances in imaging, diagnostic and overall treatment modalities have tailored the management of patients, specifically those who wish to maintain the pregnancy. The aim of this review was to provide clinicians with concise information on the management of the most common malignancies during pregnancy. We performed a review of the current literature including review articles, original research articles and guidelines, which are used for the management of the most common malignancies during pregnancy. Breast, cervical and ovarian malignant tumours are the most common during pregnancy. However, the overall outcome and survival per stage for these cancers do not appear to be influenced by pregnancy. Ethical, emotional and treatment dilemmas may be encountered during treatment planning. Individualization of treatment planning should be made by a multidisciplinary team but the final decision rests with the parents.

Definitive chemoradiotherapy for cervical cancer: A 11-year population-based study.

PURPOSE: To assess the recurrence pattern and survival in women treated with definitive chemoradiotherapy for cervical cancer. METHODS: A retrospective cohort study of women FIGO (2012) stage IB2 to IVA from the Grampian region of Scotland between February 2000 and March 2011. These women were followed up until April 2018. RESULTS: A total of 121 eligible women allocated with mean age at treatment 50.59 years (SD = 13.98, range 22-82). Tumours staged: IB2: n = 24 (19.8%), II: n = 45 (37.2%), III: n = 43 (35.5%) and IVA: n = 7 (5.8%). Two (1.7%) women had no available data. Fifty-five (45.5%) women had recurrence after treatment, and 51 (42.15%) women died from the disease. The sites of recurrence were as follows: central pelvic only (n = 4, 7.27%), pelvic and distant (n = 39, 70.91%) and distant only (n = 12, 21.82%) with median time from end of treatment to first recurrence 44 months (range 2-98), 26 months (range 1-146) and 22 months (range 3-66) respectively. 5-and 8-year overall survival was 76.0% (95% CI: 68.8%-84.0%) and 64.4% (95% CI: 56.4%-73.5%) respectively. CONCLUSIONS: Though overall survival is better than with radiotherapy alone, recurrence occurs up to 10 years after treatment. This raises the issues of how to reduce late recurrence and the appropriateness of current follow-up protocols.

An update on the use of immunohistochemistry and molecular pathology in the diagnosis of pre-invasive and malignant lesions in gynecological oncology.

OBJECTIVE: One of the most common challenges in everyday clinical practice of gynecological oncology is to identify the type and the primary origin of a tumor. This is a crucial step in the management, treatment, prognosis, and survival of patients suffering from a gynecological malignancy. Immunohistochemistry has been widely adopted over the last three decades in pathology laboratories all over the world. Recent advances in our understanding of the differentiation of gynecological tumors based on immunohistochemical expression have resulted in use of immunohistochemistry as a major diagnostic tool in gynecology, for precise tumor classification. More recently, advances in molecular pathology, have taken this disease sub-classification further resulting in more effective personalised treatment regimens. The aim of this review is to provide clinicians with up to date information on the various immunohistochemical and molecular tests used in the diagnosis of gynecological malignancies of the female genital tract and an understanding of how to interpret them. METHODS: We performed a review of the current literature including review articles, original research articles, and guidelines on various immunohistochemical markers and molecular techniques which are used for the differential diagnosis of gynecologic malignancies. CONCLUSIONS: Immunohistochemistry is useful as an objective means for improved diagnostic reproducibility, accuracy, and precise classification in cases where the diagnosis with histochemical stains is inconclusive, providing a more reliable estimate of clinical outcomes. The diagnosis, in some cases, can be further refined by the use of molecular techniques leading to personalised medical treatments.

Endometrial cancer after endometrial ablation or resection for menorrhagia.

OBJECTIVE: To assess the incidence of endometrial cancer after endometrial ablation or resection (EA/R) for menorrhagia. METHOD: The present retrospective observational cohort study included women who underwent EA/R for menorrhagia at Aberdeen Royal Infirmary between February 1, 1990 and December 31, 1997. Follow-up data until 2015 were examined. To assess risk of endometrial cancer, each woman was matched by age to the annual observed incidence of endometrial cancer in northeast Scotland for each year from the date of EA/R until 2015. RESULTS: During the 7-year study period, 901 eligible women (mean age 42.3 ± 5.7 years; range 26-50 years) underwent EA/R. Of these patients, 204 (22.6%) subsequently had a hysterectomy for reasons other than endometrial cancer, and 695 (77.1%) did not. The overall incidence of endometrial cancer was 0.2% (2/901); the risk of developing endometrial cancer after EA/R was calculated as 11.1 per 100 000 women years. The mean expected incidence for all women and the subgroup with no hysterectomy was estimated to be 26.5 and 35.6 occurrences per 100 000 women years, respectively. The observed incidence was significantly lower versus the mean expected risk for both groups (P<0.001). CONCLUSION: The findings indicate that the risk of endometrial cancer could be significantly reduced but not eliminated by EA/R.

Primary small cell ovarian cancer of pulmonary type: A case report.

BACKGROUND: Primary small cell ovarian cancer of pulmonary type (SCCOPT) is a rare aggressive ovarian tumour with an incidence of <1%, usually occurring in perimenopausal or postmenopausal women and known to have a poor prognosis. Current treatment is platinum based but has not resulted in long term survival. CASE PRESENTATION: We report a case of a 77-year old Caucasian woman who presented initially with a one-week history of abdominal discomfort with raised inflammatory markers and Ca125 of 50 µ/ml. Calcium levels were normal. She underwent primary debulking surgery, and histology showed a tumour comprising areas of classical small-cell carcinoma morphology. 6 cycles of adjuvant chemotherapy with carboplatin was offered. Relapsed/progressive disease was noted after 3 months of chemotherapy and patient died 7 months after treatment completion. CONCLUSIONS: SCCOPT is a rare aggressive malignancy with majority of the women having an overall survival of 2 years. There is no clear consensus for the diagnosis and optimal treatment.

Effect of High-Risk Human Papillomavirus but Normal Cytology at Test of Cure on Achieving Colposcopy Standards.

OBJECTIVE: In United Kingdom., test of cure after treatment of any grade of cervical intraepithelial neoplasia (CIN) incorporates high-risk human papillomavirus (Hr-HPV) test and cytology at 6-month follow-up. The aims of the study were to determine the rate of recurrent CIN in women who are Hr-HPV positive and cytology negative and to explore possible associated risk factors. METHODS: A retrospective observational cohort study was performed in women treated for any grade CIN between 2010 and 2015 from a regional population, who were Hr-HPV positive and cytology negative at first follow-up. RESULTS: A total of 2729 women were identified as treated for any grade CIN, and 213 (7.8%) were re-referred to colposcopy having Hr-HPV-positive test and negative cytology at test of cure. Their mean age was 31.56 years (range = 19-62 years). The mean time of follow-up per woman was 30.50 months (range = 2-63 months). At colposcopy, 171 (80.3%) had colposcopy examination only and 42 women (19.7%) had a biopsy. Twenty-four cases (11.3%) of CIN were identified of which 4 (1.9%) were CIN 2/3. Eleven women (5.2%) in total had a repeat treatment. Five women (2.3%) had biopsy-proven CIN 2/3 within 12-months after treatment. No cases of CIN 3+ after negative colposcopy were identified during the follow-up period. CONCLUSIONS: The incorporation of Hr-HPV testing yielded a very small number of women with residual CIN within 12 months of treatment. Our results suggest that women who are Hr-HPV positive and cytology negative after treatment of CIN with normal and adequate colposcopy could be discharged to routine recall if confirmed by larger national data.

Surgical Outcomes and Morbidity After Radical Surgery for Ovarian Cancer in Aberdeen Royal Infirmary, the Northeast of Scotland Gynaecologic Oncology Centre.

BACKGROUND/AIM: Ovarian cancer (OC) has a high mortality rate and usually presents late in advanced stage, which poses challenges to management. Better understanding of the disease biology and application of radical surgery (RS) to achieve no visible residual tumor, alongside with chemotherapy, may lead to longer survival amongst these patients. Our purpose was to examine the demographic characteristics, surgical morbidity and outcomes of patients undergoing RS for OC. MATERIALS AND METHODS: A retrospective cohort study of women undertaking surgery for OC between February 2014 and September 2016 in Aberdeen Royal Infirmary. RESULTS: A total of 121 women had surgery for OC of whom 78 (64.5%) were stage II and above. Of these, 40 (51.3%) women had primary and 38 (48.7%) had interval debulking surgery with 42 (53.8%) having radical surgery. The most common procedures that were performed as part of RS included rectosigmoid resection (n=20, 47.6%), small bowel resection (n=10, 23.8%), splenectomy (n=9, 21.4%). Morbidity outcomes included blood loss >1.5 lt. (n=14, 33.3%), hospitalization >7days (n=31, 73.8%), sepsis (n=8, 19%). There was no short-term mortality. Debulking outcomes were: no macroscopic residual disease (n=36, 85.7%), ≤10 mm disease (n=2, 4.8%), and ≥10 mm disease (n=3, 7.1%). CONCLUSION: Our findings support the practise where RS for OC can be offered to selected patients, with good surgery outcomes and low morbidity rates.