Heterogeneity of Cervical Cancer-Associated Tertiary Lymphoid Structures (TLSs) and Their Specific Interrelation With Clinicopathological Parameters.

OBJECTIVE: The study investigates morphological variants of tertiary lymphoid structures (TLSs) in relation to cervical cancer development, from intraepithelial neoplastic lesions to invasive carcinomas with locoregional lymph node metastases. MATERIALS AND METHODS: This retrospective analysis comprised 100 cervical cancer cases who had had total hysterectomy with lymphadenectomy in the Obstetrics and Gynecology Clinic of the Municipal Emergency Clinical Hospital of Timisoara, Romania, from 2020 to 2023. Bilateral ilio obturator lymphadenectomy and total hysterectomy were used to acquire biopsy samples. The presence of germinal centers, other stromal structures, TLS density, topography relative to the tumor lesion, and malignant cell islets are used to evaluate and classify TLS. RESULTS: We first globally evaluated the total number of TLSs (TLS.T). We observed topographically two places in the cervical stroma: TLS immediately peritumorally positioned and TLS away from tumor lesions. Invasive carcinomas have bigger superficial TLSs with a well-defined germinal center. As they approached the tumor, TLSs increased in size and density. We also detected a special type of TLS associated with nerve fibers, which we named tertiary lymphoid structures associated with nerves (TLS.N). The total number of TLSs did not correlate with age, but 85.71% of patients presenting TLS.N were aged between 59 and 72 years old. Our findings showed a strong correlation between age (postmenopausal, p = 0.005) and TLS-N presence. Similarly, TLS parameters evolved with tumor differentiation. Only in the TLS.N group did the tumoral grading (G) 3 correlate with TLS (p = 0.041), while TLS.T did not correlate with G. All TLS.N. patients, except one, had lymphovascular invasion and massive histiocytosis. On the first point, TLS.N correlated with lymphovascular invasion (p = 0.032). CONCLUSION: Tertiary lymphoid structures associated with nerves have not been previously reported in cervical cancer, and their effects on prognosis and aggression are unknown. There was a substantial association between TLSs.N presence and age over 60, suggesting it is exclusive to menopausal women. They were also substantially connected with lymphovascular invasion and G3, suggesting they may be a poor cervical cancer prognostic factor.

Risk Factors of Thrombophilia-Related Mutations for Early and Late Pregnancy Loss.

Background and Objectives: This retrospective cohort study investigates the role of genetic thrombophilia in pregnant women experiencing early pregnancy loss compared to those with late pregnancy loss. Materials and Methods: Participants were categorized into early and late pregnancy loss groups based on gestational age. A total of 156 patients were included, out of which 103 had early-trimester pregnancy losses and 96 had multiple miscarriages. Results: The study revealed a synergistic effect of Factor V Leiden (FVL G1691A) and Methylenetetrahydrofolate Reductase (MTHFR C677T) mutations (coefficient 3.42). Prothrombin (PT) G20210A and ß-Fibrinogen 455 G>A mutations exhibited a significant interaction (coefficient 1.98). Additionally, MTHFR A1298C and Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G) mutations showed a significant interaction (coefficient 1.65). FVL G1691A and Endothelial Protein C Receptor (EPCR) allele A1/A2 mutations also demonstrated a significant association (coefficient 2.10). Lastly, MTHFR C677T and Glycoprotein IIb/IIIa T1565C mutations interacted significantly (coefficient 1.77). Risk factor analysis identified several mutations associated with early pregnancy loss, including PAI-1 4G/5G homozygous (OR 3.01), FVL G1691A heterozygous (OR 1.85), and MTHFR A1298C heterozygous (OR 1.55). Both homozygous and heterozygous MTHFR C677T mutations were significant risk factors (OR 2.38; OR 2.06), as was PT G20210A homozygous mutation (OR 1.92). The PAI-1 4G/4G homozygous variant posed a risk (OR 1.36). Late pregnancy loss was associated with MTHFR A1298C homozygous mutation (OR 3.79), ß-Fibrinogen 455 G>A heterozygous mutation (OR 2.20), and MTHFR A1298C heterozygous mutation (OR 2.65). Factor XIII G1002T heterozygous mutation (OR 1.18) and PAI-1 4G/5G homozygous mutation (OR 2.85) were also significant risk factors. EPCR allele A1/A2 (OR 1.60) and A2/A3 (OR 1.73) mutations were identified as significant risk factors for late pregnancy loss. Furthermore, FVL G1691A homozygous mutation, PT G20210A homozygous mutation, MTHFR C677T heterozygous mutation, MTHFR A1298C heterozygous mutation, and EPCR allele A1/A2 were identified as significant risk factors for multiple miscarriage. Conclusions: This study highlights significant interactions and risk factors related to genetic thrombophilia mutations in different types of pregnancy loss, contributing valuable insights for miscarriage management guidelines.

Laparoscopic Pectopexy versus Vaginal Sacrospinous Ligament Fixation in the Treatment of Apical Prolapse.

OBJECTIVES: To compare the follow-up results of a sacrospinous ligament fixation (SSLF) technique for laparoscopic bilateral fixation of the vagina to the iliopectineal ligament via a PVDF-mesh (laparoscopic pectopexy technique, LP) in terms of cure rate and postoperative complications rate. MATERIAL AND METHODS: This prospective study included 160 patients diagnosed with pelvic organ prolapse stage II-IV according to the POP-Q system. Eighty-two patients (51.25%) underwent vaginal sacrospinous ligament fixation and seventy-eight patients (48.75%) underwent the laparoscopic pectopexy procedure. RESULTS: The cure rate was high in both groups, 95.12% of the patients (78 out of 82) in the SSLF group and 93.59% of the patients (73 out of 78) in the LP group were cured post surgery, leading to an overall cure rate of 151 out of 160 patients. Pelvic pain was present in 5.00% of all patients, but was notably more frequent in the SSLF group (7, 8.54%) than in the LP group (1, 1.28%). Dyspareunia occurred in 4.37% of all patients, slightly more frequently in the SSLF group (6, 7.32%) than the LP group (1, 1.28%), but without significant difference. CONCLUSIONS: The laparoscopic pectopexy procedure has comparably positive follow-up results with the conventional sacrospinous ligament fixation procedure. Both SSLF and LP are effective in the treatment of pelvic organ prolapse, with favorable anatomical and subjective results, a high cure rate and low rates of serious postoperative complications.

Minimizing blood loss in laparoscopic myomectomy with temporary occlusion of the hypogastric artery.

Introduction: Uterine leiomyomas are common benign pelvic tumors. Currently, laparoscopic myomectomy (LM) is the preferred treatment option for women in the fertile age group with symptomatic myomas. The authors hypothesize that combining LM with a bilateral temporary occlusion of the hypogastric artery (TOHA) using vascular clips minimizes uterine blood flow during surgery and can significantly reduce surgery-associated blood loss. Materials and methods: This single-center, prospective randomized study was conducted at the Department of Obstetrics and Gynecology, Municipal Emergency Clinical Hospital Timisoara, Romania. Patients aged between 18 and 49 who preferred laparoscopic myomectomy and wished to preserve fertility were included, provided they had intramural uterine leiomyomas larger than 4 cm in diameter that deformed the uterine cavity. The study analyzed data from 60 laparoscopic myomectomies performed by a single surgeon between January 2018 and December 2020. Patients were randomly assigned to either: "LM + TOHA" group (29 patients), and "LM" group (31 patients). The study's main objective was to evaluate the impact of TOHA on perioperative blood loss, expressed as mean differences in Hb (delta Hb). Results: Delta Hb was statistically lower in the "LM + TOHA" group compared to "LM" group, with mean ± standard (min-max): 1.68 ± 0.67 (0.39-3.99) vs. 2.63 ± 1.06 (0.83-4.92) g/dL, respectively (p < 0.001). There was a statistically significant higher need for postoperative iron perfusion in the "LM" group, specifically 0 vs. 12 patients (p < 0.001), and lower postoperative anemia in "LM + TOHA" group (p < 0.001). Necessary artery clipping time was 10.62 ± 2.47 (7-15) minutes, with no significant impact on overall operative time: 110.2 ± 13.65 vs. 106.3 ± 16.48 (p = 0.21). There was no difference in the length of hospitalization or 12-month post-intervention fertility. Discussion: Performing bilateral TOHA prior to laparoscopic myomectomy has proven to be a valuable technique in reducing surgery-associated blood loss, while minimizing complications during surgery, with no significant increase in the overall operative time. Clinical trial registration: ISRCTN registry, (www.isrctn.com), identifier ISRCTN66897343.

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies.

Vitamin D deficiency has been correlated with various conditions, including the risk of developing lymphoid malignancies. This systematic review aimed to assess the association between vitamin D levels at diagnosis of lymphoid malignancies, patient outcomes, and survival. A systematic review was conducted, encompassing 15 studies published until January 2023, involving 4503 patients, examining the relationship between vitamin D and lymphoid cancers. The median age of the patients was 56.5 years, with a median follow-up duration of approximately 36 months across studies. The overall median vitamin D level at initial measurement was 20.4 ng/mL, while a <20 ng/mL threshold was used to define vitamin D insufficiency. The results demonstrated significant associations between vitamin D levels and patient outcomes in several lymphoid malignancies, with a pooled risk in disease progression of 1.93 and a pooled hazard ratio of 2.06 for overall survival in patients with 25-(OH)D levels below the normal threshold of 20 ng/mL. Among findings, it was demonstrated that supplemental vitamin D improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. Vitamin D had a protective effect for patients with DLBCL under R-CHOP treatment, while vitamin D insufficiency was associated with the impairment of rituximab treatment and showed worse clinical outcomes in chimeric antigen receptor T-cell (CAR-T) recipients. Although one study found no association between vitamin D deficiency and the cause of death, most associated vitamin D insufficiency with early clinical failure and lower survival probability. In conclusion, his systematic review highlights the importance of vitamin D levels in the prognosis and survival of patients with lymphoid malignancies. Further research is needed to better understand the underlying mechanisms and explore the potential benefits of vitamin D supplementation in managing these cancers.

Assessment of CA-125 First-Trimester Values as a Potential Screening Marker for Pre-Eclampsia.

Background: Pre-eclampsia is a major public health issue. Current screening methods are based on maternal characteristics and medical history, but complex predictive models combining different clinical and biochemical markers have been proposed. However, although their accuracy is high, the implementation of these models in clinical practice is not always feasible, especially in low- and middle-resource settings. CA-125 is a tumoral marker, accessible and cheap, with proven potential as a severity marker in the third trimester of pregnancy in pre-eclamptic women. Assessment of its use as a first-trimester marker is necessary. Methods: This observational study involved fifty pregnant women between 11 and 14 weeks of pregnancy. Clinical and biochemical markers (PAPP-A), known for their value in pre-eclampsia screening, were recorded for every patient as well as first-trimester value of CA-125 and third-trimester data regarding blood pressure and pregnancy outcome. Results: No statistical correlation between CA-125 and first-trimester markers was observed except with PAPP-A, with which it exhibited a positive correlation. Additionally, no correlation was made between it and third-trimester blood pressure or pregnancy outcomes. Conclusions: CA-125 first-trimester values do not represent a valuable marker for pre-eclampsia screening. Further research on identifying an accessible and cheap marker to improve pre-eclampsia screening in low- and middle-income settings is needed.

Evaluating Patient Preferences and Clinical Outcomes in Stress Urinary Incontinence Treatment: A Short-Term Follow-Up Study of the Transobturator Tape Procedure and Pubourethral Ligament Plication (a Minimally Invasive Technique).

OBJECTIVE: This study aims to provide an in-depth analysis of patient preferences and clinical outcomes associated with two surgical techniques for treating stress urinary incontinence (SUI): the transobturator suburethral sling (TOT) procedure and the pubourethral ligament plication (PUL) procedure. We evaluated the rates of postoperative complications, the duration of each procedure, hemoglobin loss, and days of hospitalization. MATERIALS AND METHODS: This prospective study included 80 patients who underwent surgery for SUI: 40 patients for the TOT procedure and 40 patients for the PUL procedure. Clinical data on patient characteristics, treatment efficacy, and post-surgical outcomes were analyzed to assess patient preferences and real-world clinical effectiveness. RESULTS: Regarding patient preferences, those who underwent TOT surgery were more likely to be older, had a higher average number of pregnancies, and were more often postmenopausal, in contrast to those who underwent PUL surgery (p < 0.001 for each comparison). TOT patients had a hospital stay on average of 1.02 days, while PUL patients benefited from ambulatory stays only. In addition, the TOT group had a significantly longer average operating time (16.80 min) compared to the PUL group (9.90 min, p < 0.001). The study revealed notable outcomes in both groups, with high cure rates for both TOT (N1 = 33, 82.5%) and PUL (N2 = 28, 70%) procedures. Specifically, 76.25% of the patients (61 out of 80) were cured after the procedures. Chronic pelvic pain was present in 3.75% of all patients and was notably only observed in the TOT group, with 3 (7.5%) cases being noted. Similarly, vaginal erosion was experienced by 5% of all patients, with 10% of patients in the TOT group and none in the PUL group being affected. Dyspareunia occurred in 2.5% of all patients, with there being two (5%) cases in the TOT group and none in the PUL group. CONCLUSIONS: This study highlights that while the PUL procedure achieves cure rates comparable to TOT, it offers a less invasive option with shorter operating times and no hospitalization required. These findings suggest that PUL could be a viable alternative for stress urinary incontinence (SUI) treatment, especially in contexts where avoiding mesh use is preferred. This adds significant value to patient-centered care in SUI management, offering tailored treatment options based on patient characteristics, preferences, and risk profiles.

Role of CA-125 Level as a Marker in the Management of Severe Pre-Eclampsia.

BACKGROUND AND OBJECTIVES: Hypertensive disorders of pregnancy remain one of the leading causes of morbidity and mortality in maternal-fetal medicine worldwide, particularly in low-resource settings. Despite extensive research in the last decades, pre-eclampsia prediction and, thus, effective prevention remains an unsolved problem. Current evidence suggests that CA-125, an already recognised tumoral marker and, lately, a valuable severity marker of heart failure, can be used to evaluate pre-eclampsia severity and thus improve the identification and management of high-risk patients; Materials and Methods: This is a case-control study involving 100 pregnant patients over 25 weeks of gestation, grouped based on the severity of hypertension in gestational hypertension (n = 22), non-severe pre-eclampsia (n = 11), severe pre-eclampsia (n = 17), and a control group (normotensive) (n = 50). Clinical and biochemical parameters recommended by the international guidelines for evaluating hypertensive pregnant patients were gathered from every patient in addition to CA-125 levels. The correlation was analysed. RESULTS: Mean CA-125 levels increased with the severity of hypertension from a mean of 8.97 U/mL (±2.84) in the normotensive group to a mean of 21.23 U/mL (±11.18) in the severe pre-eclampsia group. Significant differences were observed between each group. The correlation of CA-125 levels with the assessed clinical and biochemical parameters showed positive correlations with MAP, 24 h proteinuria, and LDH values and negative correlations with platelet count, gestational age at birth, and birth weight Conclusions: The reported results support this marker's promising role as a severity marker and its potential to improve pre-eclampsia management allowing a better selection of high-risk patients, aiding in decision making related to hospitalisation and/or timing of birth. Further studies are needed to improve the accuracy of the obtained results, identify an accurate cut-off and an optimal time of measurement, and achieve standardisation in measuring the marker.

Assessing Pretransplant and Posttransplant Therapy Response in Multiple Myeloma Patients.

Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a number of treatment breakthroughs. Frontline standard-of-care has little long-term success, with the majority of patients eventually relapsing, although the overall progression-free survival (PFS) has improved significantly in the last ten years. Patients who are eligible for a transplant have the highest PFS rate at 5 years, depending on medication response and other various factors that are yet to be discovered. Therefore, the current study aimed to evaluate the response to VCD (bortezomib, cyclophosphamide, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) used as pretransplant regimens, as well as to compare responses between thalidomide and lenalidomide used as maintenance therapy posttransplant. This retrospective study was performed on a group of 105 hospitalized patients in the Hematology Department of the Timisoara Municipal Emergency Clinical Hospital between January 2016 and December 2021. Data was collected from the paper records of patients with MM who were under-followed. The treatment regimens used as induction therapy were either VCD or VTD if cyclophosphamide was contraindicated. Of the 105 patients, 27 became eligible for bone marrow transplantation. Furthermore, they received maintenance therapy which was based on either lenalidomide with dexamethasone or thalidomide with dexamethasone. Of the 62 patients treated with VTD, 17.7% were in complete remission before stem cell transplantation. Of the 43 patients treated with VCD, 37.2% were in complete remission. The 5-year mean progression-free survival (PFS) in the entire cohort was better in the group treated with the VTD regimen (31.6 vs. 27.2 months). However, in the 27 patients undergoing maintenance after ASCT, the PFS with thalidomide was 35.5 months (95% CI = 27-42), while the PFS rate in those receiving maintenance treatment with lenalidomide was 46.1 months (95% CI = 20-73). VCD proved to be superior to VTD in inducing complete pretransplant responses. Regarding maintenance therapy, patients from the lenalidomide group had superior responses compared with those under thalidomide.

New Insights in the Diagnosis of Rare Adenocarcinoma Variants of the Cervix-Case Report and Review of Literature.

We report the case of a 29-year-old patient with low-grade squamous intraepithelial lesion (L-SIL), negative human papilloma virus (HPV), positive p16/Ki-67 dual-staining and colposcopy suggestive for severe dysplastic lesion. The patient underwent a loop electrosurgical excision procedure (LEEP), the pathology report revealing mesonephric hyperplasia and adenocarcinoma. The patient also opted for non-standard fertility-sparing treatment. The trachelectomy pathology report described a zone of hyperplasia at the limit of resection towards the uterine isthmus. Two supplementary interpretations of the slides and immunohistochemistry (IHC) were performed. The results supported the diagnosis of mesonephric adenocarcinoma, although with difficulty in differentiating it from mesonephric hyperplasia. Given the discordant pathology results that were inconclusive in establishing a precise diagnosis of the lesion and the state of the limits of resection, the patient was referred to a specialist abroad. Furthermore, the additional interpretation of the slides and IHC were performed, the results suggesting a clear cell carcinoma. The positive p16/Ki-67 dual-staining prior to LEEP, the non-specific IHC and the difficulties in establishing a diagnosis made the case interesting. Given the limitations of cytology and the fact that these variants are independent of HPV infection, dual staining p16/Ki-67 could potentially become useful in the diagnosis of rare adenocarcinoma variants of the cervix, however further documentation is required.

Case Report: Laparoscopic Isthmocele Repair on an 8 Weeks Pregnant Uterus.

An isthmocele, also known as a caesarean scar defect, is a long-term complication of caesarean sections with an increasing incidence. Although is often asymptomatic, it is a novel recognised cause of abnormal uterine bleeding, and it is a major risk factor for caesarean scar pregnancies or uterine ruptures in subsequent pregnancies. Currently there are no guidelines for the diagnosis and management of this condition. Several surgical techniques for the correction of isthmocele are proposed, including laparoscopic excision, vaginal repair, a combined laparoscopic-vaginal approach or more recently hysteroscopic resection. We present the case of a GII PI, 29 years old patient with a previous c-section who presented in our clinic with a positive pregnancy test for pregnancy confirmation. The ultrasound examination revealed an intrauterine evolutive 8 weeks pregnancy and a caesarean scar defect. After counselling the patient opted for pregnancy continuation and laparoscopic correction of the isthmocele. The surgery was performed under ultrasound guidance. The defect was resected, and the uterus was closed with a continuous two-layer suture. No intraoperative or postoperative complications were present. The pregnancy continued uneventfully A caesarean section was performed at term revealing a fully healed scar.

Role of Dual-Staining p16/Ki-67 in the Management of Patients under 30 Years with ASC-US/L-SIL.

Patients diagnosed with low-grade squamous intraepithelial lesion ((L-SIL) or atypical squamous cells of undetermined significance (ASC-US) are subjected to additional investigations, such as colposcopy and biopsy, to rule out cervical intraepithelial neoplasia 2+ (CIN 2+). Especially in young patients, lesions tend to regress spontaneously, and many human papilloma virus (HPV) infections are transient. Dual-staining p16/Ki-67 has been proposed for the triage of patients with ASC-US or L-SIL, but no prospective study addressing only this subgroup of patients has been conducted so far. We performed a prospective study including all eligible patients referred for a loop electrosurgical excision procedure (LEEP) in the Department of Obstetrics and Gynecology of Timișoara University City Hospital. HPV genotyping and dual-staining for p16/Ki-67 were performed prior to LEEP, at 6 and 12 months after LEEP. A total of 60 patients were included in the study and completed the follow-up evaluation. We analyzed the sensitivity and specificity for biopsy-confirmed CIN2+ using the 95% confidence interval (CI) of high-risk human papilloma virus (HR-HPV), dual-staining p16/Ki-67, colposcopy, and combinations of the tests on all patients and separately for the ASC-US and L-SIL groups. Dual-staining p16/Ki-67 alone or in combination with HR-HPV and/or colposcopy showed a higher specificity that HR-HPV and/or colposcopy for the diagnosis of biopsy confirmed CIN2+ in patients under 30 years. Colposcopy + p16/Ki-67 and HR-HPV + colposcopy + p16/Ki-67 showed the highest specificity in our study.

A Case Report of Left Atrial Isomerism in a Syndromic Context.

The objective of our paper is to underline the importance of assessing microarray genetic analysis for the detection of chromosomal abnormalities in rare cases such as left atrial isomerism, mostly in the context of antenatally detected syndromes. We present the case of a 26-year-old primipara, at 26 weeks of gestation, with prior first trimester normal anomaly scan, who presented in our department accusing lower abdominal pain. An anomaly ultrasound examination of the fetus revealed cardiomegaly with increased size of the right atrium, non-visualization of the atrial septum or the foramen ovale, malalignment of the three-vessel view, location of the superior vena cava above the two-vessel view, slight pericardial effusion, and no interruption of the inferior vena cava nor presence of azygos vein being noted. Associated extracardiac abnormalities, such as small kidneys at the level of the iliac fossa, micrognathia, dolichocephaly with hypoplasia of the cerebellum, increased nuchal fold, and reduced fetal movements were also reported. A diagnostic amniocentesis was performed, and, while the conventional rapid prenatal diagnostic test of the multiplex quantitative fluorescent polymerase chain reaction (PCR) came as normal, the microarray analysis (ChAS, NCBI Built 37 hg 19, detection of microdeletions or microduplications larger than 100 kb) revealed two chromosomal abnormalities: a 22.84 Mb loss of genetic material in the 18q21.31-18q23 chromosomal region and a gain of 22.31 Mb of genetic material in the 20p13-20p11.21 chromosomal region. After the termination of pregnancy, a necropsy of the fetus was performed, confirming heterotaxy syndrome with a common atrium, no atrial septum, superior vena cava draining medianly, and pulmonary veins that drained into the lower segment of the left atrium due to an anatomically enlarged single common atrium. The extracardiac findings consisted of two bilobar lungs, dysmorphic facies, low-set ears, nuchal fold edema, and small kidneys located in the iliac fossa. These findings are conclusive evidence that left atrial isomerism is a more complex syndrome. The genetic tests of the parents did not reveal any translocations of chromosomes 18 and 20 when the Fluorescent in situ Hybridization (FISH) analysis was assessed. The antenatal detection of corroboration between different structural abnormalities using serial ultrasound examinations and cardiac abnormalities, together with the detection of the affected chromosomes, improves the genetic counseling regarding the prognosis of the fetus and the recurrence rate of the condition for siblings.

Endometriosis in Menopause-Renewed Attention on a Controversial Disease.

Endometriosis, an estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial tissue, has been the topic of renewed research and debate in recent years. The paradigm shift from the belief that endometriosis only affects women of reproductive age has drawn attention to endometriosis in both premenarchal and postmenopausal patients. There is still scarce information in literature regarding postmenopausal endometriosis, the mostly studied and reported being the prevalence in postmenopausal women. Yet, other important issues also need to be addressed concerning diagnosis, pathophysiology, and management. We aimed at summarizing the currently available data in literature in order to provide a concise and precise update regarding information available on postmenopausal endometriosis.

p16/Ki-67 dual staining has a better accuracy than human papillomavirus (HPV) testing in women with abnormal cytology under 30 years old.

Due to a high rate of transient human papillomavirus (HPV) infection, HPV genotyping has a low specificity for high-grade cervical lesions, especially in young women. p16/Ki-67 dual immunocytochemical staining can also be used for the detection of oncogenic changes in cervical cells. Our aim was to compare the performance of p16/Ki-67 dual staining and HPV genotyping in the detection of high-grade cervical lesions in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We retrospectively analyzed 310 patients with ASCUS/LSIL on Pap smear, who underwent colposcopy. Among these, 161 patients with suspected lesions detected by colposcopy were referred for biopsy. HPV genotyping by LINEAR ARRAY HPV Genotyping Test (CE-IVD) and p16/Ki-67 dual staining by CINtec PLUS Cytology kit was performed prior to cervical biopsy. The overall sensitivity and specificity of HPV genotyping for the detection of cervical intraepithelial neoplasia (CIN) 2-3 was 79% and 72%, respectively in patients with ASCUS, and 85% and 64%, respectively in patients with LSIL. For p16/Ki-67 test, sensitivity and specificity rate was 66% and 93%, respectively in ASCUS and 59% and 79%, respectively in LSIL group. The specificity of p16/Ki-67 staining was significantly higher in both groups in patients aged <30 years compared to patients >30 years old (p < 0.001). Our results showed that p16/Ki-67 dual staining has a higher specificity compared to HPV genotyping, especially in patients under 30 years old. This indicates the usefulness of p16/Ki-67 testing in the triage of patients with ASCUS/LSIL and <30 years old, prior to referral for colposcopy and biopsy.

Laparoscopic Resection of Cesarean Scar Ectopic Pregnancy after Unsuccessful Systemic Methotrexate Treatment.

STUDY OBJECTIVE: To present a case of a cesarean scar ectopic pregnancy treated by laparoscopic resection followed by isthmocele repair. DESIGN: A case report. SETTINGS: The University Gynecology Clinic of the Emergency Clinical City Hospital Timișoara, Timișoara, România. BACKGROUND: Cesarean scar pregnancy is a rare form of ectopic pregnancy. In recent years, its prevalence has risen because of the increasing number of cesarean sections. An early diagnosis can lead to early management, decreasing the risk of life-threatening complications such as uterine rupture and massive hemorrhage. Many therapeutic options are available, medical and surgical, but the current literature suggests that the laparoscopic approach with ectopic pregnancy resection is the best option. CASE REPORT: We present the case of a 30-year-old woman with a previous cesarean section in 2012 who was diagnosed by transvaginal ultrasound with a 6-week live pregnancy implanted at the level of the cesarean scar. The initial management was the administration of a 2-dose methotrexate protocol, but after 72 hours the transvaginal ultrasound showed an embryo with cardiac activity still present associated with an increased beta human chorionic gonadotropin level. We decided on laparoscopic surgical treatment, aiming to extract the pregnancy and repair the scar defect. A similar case was presented by Mahgoub et al [1], but their case had a different evolution, with decreasing levels of hCG. INTERVENTIONS: In order to reduce the blood loss, the anterior trunks of the hypogastric arteries were clipped. The side wall peritoneum was cut bilaterally, and the ureters and the hypogastric arteries were dissected. Next, we performed the dissection of the vesicouterine space. Because of the previous cesarean section, the identification of the correct dissection plane was difficult. A uterine manipulator was used to facilitate the dissection. The exact location of the gestational sac was demonstrated using intraoperative transvaginal ultrasound. To reduce the bleeding, Glypressin (Ferring GmbH, Saint Prex, Switzerland) was injected at the level of the uterine scar. The cesarean scar was cut using a monopolar knife. The gestation sac was reached easily and then extracted from the abdominal cavity with the use of an endobag. In order to obtain proper healing, the margins of the scar were resected using cold scissors. The hysterotomy was closed using a double-layered suture with 2.0 Vicryl (Ethicon Inc., Cincinnati, OH). We used methylene blue to verify the tightness of the suture. The final step was the removal of the clips. MEASUREMENTS AND MAIN RESULTS: The operative time was 85 minutes with minimal blood loss of about 20 mL. The patient recovered well and was discharged 2 days after the procedure. A transvaginal ultrasound was performed 1 month after the surgery showing good healing of the anterior uterine wall. CONCLUSION: The laparoscopic approach with excision and repair of the uterine wall represents a safe and efficient therapeutic option for the treatment of the cesarean scar ectopic pregnancy.

HPV genotyping and p16÷Ki-67 dual staining in the detection of high-grade cervical lesion in patients with LSIL on Pap smear.

p16÷Ki-67 dual-stained cytology, either alone or combined with human papillomavirus (HPV) 16÷18 genotyping, could be a useful tool for triage for colposcopy of HPV-positive patients. Based on this background, we aimed at comparing the diagnostic performance of the p16÷Ki-67 dual staining test, and high-risk HPV test for the detection of high-risk cervical intraepithelial neoplasia (CIN2÷3) in patients diagnosed with low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We performed a retrospective study including 184 patients with LSIL cytology on Pap smear, of which 64 were referred for biopsy after colposcopy. Prior biopsy HPV genotyping and dual staining test were performed on all 64 patients. The mean age of the patients selected for conization was 36 years and seven months. The pathological exam showed that 28.13% (18÷64) from the patients LSIL on cytology were actually having CIN2÷3: 12 cases with CIN2, five cases with CIN3 and one case of in situ cervical carcinoma. HPV positive were 56.25% (36÷64) of the patients with LSIL. The p16÷Ki-67 dual staining test was positive in 29.69% (19÷64) of the patients with LSIL. Among women with LSIL cytology, the sensitivity and specificity of the HPV genotyping test for predicting CIN2÷CIN3 were 94.44% (17÷18) and 58.7% (27÷46), respectively. The sensitivity and specificity of the p16÷Ki-67 dual staining test were 66.67% (12÷18) and 84.78% (39÷46), respectively. Our results agree with other data available in literature and suggest that the p16÷Ki-67 dual staining test could be included in the management protocol of patients with modified cytology as a triage test before referring those patients for colposcopy.

Laparoscopic Promontohysteropexy During Pregnancy.

STUDY OBJECTIVE: To present a case of uterine prolapse in a pregnant patient at 10 weeks of gestation who was successfully treated by laparoscopic promontohysteropexy. To our knowledge, this is the first case of laparoscopic promontopexy during pregnancy to be reported in the literature. DESIGN: Step-by-step description of the surgery using videos (Canadian Task Force classification 3). SETTING: Uterine prolapse is a rare condition in young patients and is extremely rare in pregnant women. The reported incidence of uterine prolapse during pregnancy is 1/10,000 to 15,000 deliveries [1]. To date, only a few cases of prolapse during pregnancy have reported in the literature, most of which were treated with pessary insertion. A case involving laparoscopic surgery for uterine prolapse during pregnancy was reported by Matsumoto et al 1999 [2], but the authors did not perform the promontohysteropexy technique. INTERVENTION: A 27-year-old patient with uterine prolapse at 10 weeks of gestation was referred to our clinic for severe pelvic pain. Conservative treatment with pessary insertion was attempted but failed. Consequently, the patient was scheduled for laparoscopic promontohysteropexy. The surgery was made difficult by the increased size and softness of the uterus. To create an adequate surgical field, the sigmoid colon and right adnexa were suspended at the abdominal wall. The peritoneum above the promontorium was incised, and the longitudinal ligament was dissected. The paravesical spaces were opened, and the vesicovaginal space was dissected. A polypropylene mesh in the shape of an inverted "T" was introduced. The small arm was sutured to the anterior vaginal wall, and the posterior arms were passed through the posterior leaves of the broad ligament and fixed to the cervix at the level of the uterosacral ligaments. Both posterior arms were fixed at the level of the promontory using the Protack device (Medtronic, Minneapolis, MN). The mesh was completely covered with peritoneum. The patient was discharged 3 days after surgery, with no pain and with normal pelvic floor status. The pregnancy proceeded uneventfully, and she delivered a 3500-g healthy baby by scheduled cesarean section at 39 weeks of gestation. During surgery, the position of the mesh around the uterus was assessed. The mesh was completely covered with peritoneum, and there were no adhesions due to mesh insertion. At 6 months after delivery, pelvic floor status was reassessed and found to be normal. Written informed consent for reporting this case was obtained from the patient before the procedure. The procedure was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The Institutional Review Board and Ethical Committee of Victor Babes University of Medicine and Pharmacy ruled that approval was not required for this study. CONCLUSION: Laparoscopic promontohysteropxy can be performed during pregnancy if conservative treatment, such as pessary insertion, fails to restore the normal pelvic floor status.

The importance of immunocytochemistry in the detection of high-grade cervical lesions.

Despite the implementation of various screening programs in many countries, cervical cancer continues to be a major health problem. Cervical cytology is the most used screening method, but human papillomavirus (HPV) genotyping, alone or in combination with cytology, has gained ground during the last years. Still, one of the major limitations of HPV-genotyping is the low specificity of HPV as a screening method in young women that are HPV-positive, but with no potential for future disease. Obviously, there is a need for a better screening algorithm. The ideal screening test for cervical high-grade lesions should detect the effect of high-risk (HR)-HPV infection after cell transformation, but not before, and should accurately identify the cases that are more likely to experience disease progression to neoplasia. Solid data regarding the benefit of immunocytochemistry in the evaluation of the patients with modified cervical cytology have been published recently. The use of the dual staining with p16INK4a and Ki-67 could increase specificity of the method for the detection of atypical cells and may perform better in predicting the risk of high-grade dysplasia in the near future.

Age and HPV type as risk factors for HPV persistence after loop excision in patients with high grade cervical lesions: an observational study.

BACKGROUND: Persistent infections with high risk human papillomaviruses (HR-HPV) cause virtually all cervical cancers. METHODS: An observational study was conducted aiming to estimate the rate of HPV infection persistence after LEEP in patients with high grade squamous intraepithelial lesions (HSIL). Moreover, the study investigated if persistence is age related. For this reason a total of 110 patients were included between January 2010 and June 2015. RESULTS: At 6 months after LEEP the overall HPV infection persistence rate was 40.9 %, at 12 months 20 % and at 18 months 11.8 %. Type 16 showed the highest persistence rate: 27.3 % at 6 months, 12.7 % at 12 months and 10 % at 18 months after LEEP. The persistence for HPV type 16 at 6 months after LEEP was significantly higher in the group > =36.5 years old compared to the persistence rate in the group <36.5 years old (p = 0.0027, RR = 2.75, 95 %ϵ(1.34; 5.64)) (see Table 3). CONCLUSIONS: LEEP does not completely eradicate HPV infection. HPV persistence rate after LEEP is higher in infections with type 16 and in women older than 36.5 years.