History and Perspectives of Hyperradical, Laterally Extended Parametrectomy (LEP).

Cervical cancer has been and still is a major global health problem and a major treatment challenge for which surgical interventions have played a key role throughout the past century. In early stages (I/A2-II/B), where high-risk factors are not present, the efficacy of surgical and radiotherapy treatment has been considered equivalent with different (treatment modality specific) complications and quality of life consequences. Negative prognostic factors in early stages of the disease (pelvic lymph-node positivity) and in more advanced stages (parametrial and/or surgical margins' tumor involvement) forecast the deterioration of outlooks for good life expectancy. In these high-risk cases, when radio- or chemoradiotherapy is contraindicated, we investigated the potential role of a more radical surgical approach than the traditional radical hysterectomy. Twenty-five years ago, a hyperradical surgical procedure for the treatment of high-risk cervical cancer patients was introduced in Budapest. The procedure was named as laterally extended parametrectomy (LEP) in Budapest Hungary. The surgical intention was the complete removal of the fibro-fatty tissue content of the pelvis, which contains the lymphatic vessels, lymph nodes, and tumor-affected pelvic side wall structures. We initiated observational studies on the primary treatment in parametrium and/or lymph-node tumor-positive early-stage cases and on second-line surgical therapy of pelvic side wall recurrent tumors following radiotherapy. Promising results of our observational studies propose that prospective randomized trials are worth to be initiated to clarify the potential of this treatment modality in this poor prognosis cohort of patients.

[Endometrial cancer: our experience with roboticassisted technique]. / Endometriumkarcinóma ­ robotasszisztált technikával szerzett tapasztalataink.

Endometrial carcinoma is the most common type of gynaecological cancer. Its primary incidence is highest around the age of 60. The majority of cases are detected at an early stage and therefore have a good prognosis. The majority of patients suffer from obesity, which makes primary surgical treatment difficult. Minimally invasive surgery, as recommended by international protocols, is the first choice for appropriate surgical treatment and significantly reduces the incidence of complications for patients. Robotic techniques are particularly important in the care of patients with often abnormal obesity. In this article, we summarise our knowledge of endometrial carcinoma and our experience with da Vinci robot-assisted surgery, which started almost 2 years ago at Semmelweis University.

Management of Malignant Bowel Obstruction in Patients with Gynaecological Cancer: A Systematic Review.

Objectives: This systematic review aimed to evaluate current surgical and non-surgical management strategies for malignant bowel obstruction (MBO) in patients with gynaecological cancer. Methods: Comprehensive literature searches were conducted across MEDLINE, Embase, CENTRAL, and Scopus, without restrictions on language or publication date. Following the removal of duplicates, 4866 articles were screened, with 34 meeting the inclusion criteria. Results: Surgical intervention remains the definitive treatment for MBO, offering longer symptom-free periods and improved survival, particularly when conservative methods fail. However, the selection of surgical candidates is crucial due to the high risk of morbidity and the potential for significant complications. Non-surgical treatments, such as the use of Gastrografin, Octreotide, and Dexamethasone, along with invasive procedures like nasogastric tubing, percutaneous gastrostomy, and stent placement, offer varying degrees of symptom relief and are often considered when surgery is not feasible. Conclusions: In this article we provide a potential therapeutic algorithm for the management of patients with MBO. This review underscores the urgent need for high-quality research to develop clear, evidence-based guidelines for MBO management in patients with gynaecologic cancer. Establishing standardised protocols will improve patient outcomes by aiding clinicians in making informed, individualised treatment decisions.

Comprehensive Evaluation of a Levonorgestrel Intrauterine Device (LNG-IUD), Metformin, and Liraglutide for Fertility Preservation in Endometrial Cancer: Protocol for a Randomized Clinical Trial.

Endometrial cancer is a leading gynecological malignancy, with obesity being a significant risk factor due to increased estrogen production in body fat. Current treatments often involve hysterectomy, which precludes fertility, thus highlighting the need for fertility-preserving options. This study aims to evaluate the combined efficacy of a levonorgestrel intrauterine device (LNG-IUD), metformin, and liraglutide for treating women with endometrial hyperplasia or early stage endometrial cancer while preserving fertility. The study will enroll 264 women aged 18-45 with a BMI > 30 who desire uterine preservation. Participants will be randomized into three groups: LNG-IUD alone, LNG-IUD plus metformin, and LNG-IUD plus metformin and liraglutide. Primary outcomes will include complete pathological remission, while secondary outcomes will assess histological changes, glucose, insulin levels, and weight changes over a 12-month period. This study protocol hypothesizes that LNG-IUD combined with metformin and liraglutide may potentially lead to higher regression rates of endometrial hyperplasia (EH) and early stage endometrial cancer (EC) compared to LNG-IUD alone. Furthermore, the protocol anticipates that these combination therapies will demonstrate good tolerability with minimal adverse effects, suggesting the potential benefit of integrating metabolic interventions with LNG-IUD to enhance treatment efficacy while preserving fertility in women with EH and EC.

Sociodemographic and Medical Characteristics of Women Applied for Emergency Contraception-A Retrospective Observational Study.

Background: Lifestyle factors significantly impact overall health. Our aim was to assess reproductive health awareness among patients who applied for emergency contraceptive pills. Methods: This present retrospective observational study between July 2021 and September 2021 is embedded in the MEEC (Motivation and Epidemiology of Emergency Contraceptive Pill) based on the study cohort of a Hungarian data bank containing follow-up data of 447 women who applied for EC telemedicine consultation. Collected data: age, history of previous pregnancy, lifestyle factors like smoking, alcohol consumption, sexual characteristics: partner consistency and protection during intercourse, cervical cancer screening within the past 2 years, previous HPV screening, and the preference for future contraceptive methods. The investigation also compiled accurate data on intercourse (elapsed time to request a medical consultation). Lifestyle factors were scored. Results: The more health-conscious patients were quicker to report for a post-event pill. Earlier pregnancies and older age were associated with greater reproductive health awareness. Conclusions: Reproductive health awareness is increased by previous pregnancies and older age. More health-conscious women consult a doctor earlier, which can reduce the chance of various health damage. Our study emphasizes the significance of lifestyle factor influence on reproductive health decisions.

PARP inhibitor era in ovarian cancer treatment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer. METHODS: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses. RESULTS: In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases. CONCLUSIONS: PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.

Use of abdominal radical trachelectomy to treat cervical cancer greater than 2 cm in diameter.

OBJECTIVE: Invasive cervical cancer is one of the most common cancers, with 500,000 new cases diagnosed annually. Fertility preservation has become an important component of the overall quality of life of many cancer survivors. Expert opinion has suggested that fertility-sparing surgery should be limited to those patients diagnosed with cervical cancer less than 2 cm in diameter. Our objective was to report our abdominal radical trachelectomy (ART) experience in the opposite group of patients-those with a cervical cancer more than 2 cm in diameter. METHODS: Between 1999 and 2006, a total of 45 patients with cervical carcinoma at International Federation of Gynecology and Obstetrics stage IB1-IB2 measuring more than 2 cm in diameter underwent fertility-sparing ART and pelvic lymphadenectomy at the 3 institutions where the authors are based (Budapest, Hungary; London, United Kingdom; New York, United States). They were followed up for more than 5 years. RESULTS: For 69% of patients (n = 31), completed ART was considered to have been curative, and no adjuvant treatment was advised. Of those patients, 93.5% (n = 29) were alive at the time of follow-up. Thirty-one percent of patients (n = 14) underwent immediate completion of radical hysterectomy. Three of 8 patients who wished to fall pregnant delivered healthy neonates. CONCLUSIONS: The 5-year survival rate (93.5%) for this case series is equal (or better) to rates reported in the literature for patient treated with radical hysterectomy. Our survival data seem to support the hypothesis that ART is a safe treatment option for patients with invasive cervical cancer lesions of more than 2 cm.

Trichomonas vaginalis infection is associated with increased risk of cervical carcinogenesis: A systematic review and meta-analysis of 470 000 patients.

BACKGROUND: Trichomonas vaginalis infection is the most prevalent non-viral sexually transmitted infection (STI) in women and has been suggested as a risk factor for developing cervical cancer. OBJECTIVE: We aimed to investigate the associations between T. vaginalis infection and cervical carcinogenesis. SEARCH STRATEGY: A comprehensive systematic search was conducted in five databases on 21 October 2021. SELECTION CRITERIA: Studies assessing the relationship between T. vaginalis infection, HPV co-infections, cervical dysplasia, and cervical cancer were found eligible. DATA COLLECTION AND ANALYSIS: Summary estimates for pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with a random-effects model. Statistical heterogeneity was measured with I2 and Cochran's Q tests. MAIN RESULTS: The 29 articles included 473 740 women, of whom 8518 were T. vaginalis-positive. Our results showed that T. vaginalis-infected women had 1.79 times higher odds of being diagnosed with HPV co-infection (95% CI 1.27-2.53; I2 95%). We also found that T. vaginalis infection was associated with high-grade squamous intraepithelial lesion diagnosis (OR 2.34, 95% CI 1.10-4.95; I2 75%) and cervical cancer (OR 5.23, 95% CI 3.03-9.04; I2 3%). CONCLUSIONS: Our results showed an association between T. vaginalis and cervical carcinogenesis in sexually active women.

Surgical treatment of stage IB cervical cancer.

INTRODUCTION: Recurrence originating from the pelvic lymph node containing fibro-fatty tissue has consistently been identified as the most frequent pattern of treatment failure in early-stage cervical cancer. A surgical technique for the complete removal of the connective tissue content of the pelvis was introduced at St. Stephen Hospital in 1993 to improve oncological outcome by reducing the risk of recurrence from the pelvis. Efficacy and toxicity of the procedure were studied in 563 patients with stage IB cervical cancer with a completed 5-year follow-up. METHODS: Final pathology in 492 (87.4%) of 563 consecutive completed radical hysterectomies suggested that all tissue, which could contain tumor dissemination, was removed from the pelvis; thus, no adjuvant treatment was applied. Adjuvant chemoradiotherapy was advised in 71 cases (12.6%), where pathologic finding alluded tumor spread beyond the study criteria. FINDING: At completed 5-year follow-up, the overall survival of 492 patients who had surgery without adjuvant therapy was 94.0%. Pathologic stage, lymphovascular space involvement, pelvic lymph node metastases, histology classification, and grade had no significant influence on prognosis. The only factor that influenced the overall survival was International Federation of Gynecology and Obstetrics stage (IB1 or IB2). Five-year overall survival of 71 patients to whom adjuvant therapy was recommended was 56.3%. Five-year overall survival of the whole cohort (n = 563) was 88.8%. The complication rate did not seem to be different from the published data on traditional radical surgery in cervical cancer. CONCLUSIONS: Our results (in accordance with other recent publications) suggest that complete excision of the connective tissue content of the pelvis provides equal or better survival chances without any adjuvant treatment for almost 90% of operable patients with stage IB cervical cancer than less radical surgery with or without adjuvant treatment. We suggest this strategy to be mentioned as one alternative in future treatment protocols.

[Different radical surgical treatment of cervical cancer based on the histopathological characteristics of the tumour]. / A méhnyakrák különbözo radikalitású mutéti kezelése a daganat hisztopatológiai jellemzoi alapján.

The surgical treatment of cervical tumours is a complex problem that often puzzles the gynaecological surgeon. The operation was previously named after Ernst Wertheim, who performed the first radical hysterectomy more than a century ago, and has since undergone many modifications. Today, almost 50% of patients are diagnosed at an early stage, when the disease is still localised to the cervix, with a 5-year survival rate of more than 90%. Surgical treatment is the first-line treatment for this group of patients, which offers a good solution in terms of long-term quality of life through ovarian preservation and surgical technique. In the majority of cases where fertility preservation is not an option, radical removal of the uterus and removal of lymph nodes is the basis for surgery. For both interventions, there have been many changes in the last decades and a detailed description of these changes and treatment planning is the main aim of this study.

[The need, potential and unresolved issues of fertility preservation in the early stages of cervical cancer]. / A méhnyakrák korai stádiumaiban a fertilitás megtartásának igénye, lehetoségei és lezáratlan kérdései.

In the choice of a planned fertility preservation procedure for stage IA1 and IB1 cervical cancer, optimal oncological safety is the main focus of virtually all protocols. The surgeon should remove the appropriate proportion of the cervix for oncological safety, ensuring an adequate tumour-free surgical margin. However, some of the literature on fertility preservation, referring to histological parameters, still considers conisation with excellent fertility results to be optimal for the treatment of tumours with a diameter of 2 cm. With regard to fertility preservation in the case of radical trachelectomy versus simple conisation, we are aware of several ongoing studies, the results of which may provide an answer as to whether a more conservative surgical therapy for smaller tumours (less than 2 cm in diameter) represents an acceptable oncological safety.

First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects: A Systematic Review and Meta-Analysis.

Viral infections during pregnancy raise several clinical challenges, including birth defects in the offspring. Thus, this systematic review and meta-analysis aims to prove and highlight the risk of birth defects after first-trimester maternal influenza infection. Our systematic search was performed on 21 November 2022. Studies that reported maternal influenza infection in the first trimester and non-chromosomal congenital abnormalities were considered eligible. We used odds ratios (OR) with 95% confidence intervals (CIs) to measure the effect size. Pooled ORs were calculated with a random effects model. Heterogeneity was measured with I² and Cochran's Q tests. We found that first-trimester maternal influenza was associated with increased odds of developing any type of birth defects (OR: 1.5, CI: 1.30-1.70). Moreover, newborns were more than twice as likely to be diagnosed with neural tube defects (OR: 2.48, CI: 1.95-3.14) or cleft lip and palate (OR: 2.48, CI: 1.87-3.28). We also found increased odds of developing congenital heart defects (OR: 1.63, CI: 1.27-2.09). In conclusion, influenza increases the odds of non-chromosomal birth defects in the first trimester. The aim of the present study was to estimate the risk of CAs in the offspring of mothers affected by first-trimester influenza infection.

Laterally extended parametrectomy.

OBJECTIVE: To describe the laterally extended parametrectomy (LEP) surgical technique, emphasizing the main challenges of the procedure. METHODS: LEP was designed as a more radical surgical procedure aiming to remove the entire parametrial tissue from the pelvic sidewall. Its initial indications were for lymph node positive Stage Ib (current International Federation of Gynecology and Obstetrics 2018 Stage IIIc) and Stage IIb cervical cancer. Currently, with most guidelines recommending definitive radiochemotherapy for these cases, initial LEP indications have become debatable. LEP is now mainly indicated for removing tumors involving the soft structures of the pelvic sidewall during a pelvic exenteration, aiming to obtain lateral free margins. This expands the lateral borders of the dissection to not only the medial surface of internal iliac vessels, but also to the true limits of the pelvic sidewall. RESULTS: During LEP, the parietal and visceral branches of the hypogastric vessels are divided at the entry and exit level of the pelvis. Consequently, the entire internal iliac system is excised, and no connective or lymphatic tissue remain on the pelvic sidewall. The main technical challenges of LEP are caused by the difficulty in ligating large caliber vessels (internal iliac artery and vein) and the variable anatomic distribution of pelvic sidewall veins. CONCLUSION: LEP is a feasible technique for removing pelvic sidewall recurrences, aiming to obtain surgical free margins.

[Hindgut cyst in the presacral region]. / Praesacralis utóbélcysta.

Authors review a case of a 53 years old female patient with a cystic alteration 9 cm in diameter, located in the presacral region, in the medial line. Histological examination proved the mass to be a quite rare hindgut cyst which during surgery, however, did not show any connection with the rectum. The case is reported due to its relative rareness and the differential diagnostic questions emerging.