Malignant mixed Müllerian tumor of the fallopian tube: Case report and literature review.

Carcinosarcoma, also known as malignant mixed Müllerian tumor (MMMT), includes both malignant epithelial and mesenchymal elements. While the endometrium is the most frequent known site for carcinosarcomas, their development in the fallopian tube is rare condition, only accounting for 0.1 to 0.5% among all gynecological malignancies. Fallopian tube MMMT is associated with an aggressive progression. A total of 94 previous case reports were reviewed and divided, after applying the exclusion criteria, into 2 groups: No evidence of disease (NED) Group including 33 patients reported to be without any residual disease at the end of the follow-up period; death of disease (DOD) Group including 51 patients who died due to the progression of fallopian carcinosarcoma or its complications. The gathered data were statistically analyzed together with a case from our clinical experience: a 65-year-old postmenopausal patient with a final histological diagnosis of fallopian carcinosarcoma staged FIGO IC2, synchronous with a serous endometrial intraepithelial carcinoma. Patient age between 41 and 60 years, symptoms at presentation and computed tomography (CT)/magnetic resonance imaging (MRI) tumor evidence are prognostic factors (P<0.05). Omentectomy [odds ratio (OR)=0.3545] and pelvic lymphadenectomy (OR=0.3732) were found to be significant factors for survival (P<0.05). Fimbrial localization of the tumor is a negative prognosis factor (OR=4.263), as well as the heterologous type of tumor (OR=2.880). Chemotherapy was found to improve survival (OR=0.2679) while radiotherapy had no influence on patient prognosis. Reporting these rare cases could be essential for obtaining more precise information regarding the treatment and prognosis of patients with MMMT of the fallopian tube, in order to improve patient survival and quality of life.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Primary pelvic exenteration: Our experience with 23 patients from a single institution.

This study was designed with an aim to share our experience of primary pelvic exenterations. The study included 23 patients with different types of pelvic cancer enrolled at a single institution between November 2011 and July 2020. The patient mean age was 55 years (range, 43-72 years) and the oncological indications included: Stage IVa cervical cancer (11 cases, 48.9%), stage IVa endometrial cancer (1 case, 4.3%), stage IVa vaginal cancer (6 cases, 26%), stage IIIb bladder cancer (3 cases, 13%), stage IIIc rectal cancer (1 case, 4.3%) and undifferentiated pelvic sarcoma (1 case, 4.3%). Total, anterior, and posterior pelvic exenterations were performed on 34.4, 56.5 and 13% of cases, respectively. Related to levator ani muscle, 13 (56.5%) pelvic exenterations were supralevatorian, 10 (43.5%) infralevatorian, and 5 (21.7%) were infralevatorian with vulvectomy. No major intraoperative complications occurred. Seven patients (30.5%) developed early complications, 4 of them (17.4%) required reoperation and 1 (4.3%) perioperative death caused by a pulmonary embolism was recorded. Only 1 patient experienced a late complication, a urostomy stenosis. Over a median follow-up period of 35 months, 8 (34.8%) patients died. The median overall survival (OS) was 33 months (range, 1-96 months). The 2-year and 5-year survival rates were 72 and 66%, respectively. Primary pelvic exenteration may be related with various postoperative complications, without high perioperative morality and with long-term survival.

Abdominal radical trachelectomy as fertility-sparing management for early stages of cervical cancer: Our experience in 18 cases.

The aim of this study was to present our experience of 18 cases of abdominal radical trachelectomy (ART), including 5 performed during pregnancy, analyzing patient selection, surgical complications, and oncological and obstetrical outcomes. This reproductive study included all early stage cervical cancer patients referred for ART at the 1st Obstetrics and Gynecology Clinic of the Emergency Clinical County Hospital Targu Mures, between 2010 and 2020. A total of 19 women were considered for ART, and only 1 case required conversion to radical hysterectomy. The patient mean age was 31 years (range 24-38 years), and 66.67% of the patients were nulliparous. Six women (33.33%) had stage IA2, 4 (22.22%) had stage IB1, 5 (27.78%) had stage IB2, and 4 (22.22%) had stage IB3 disease. One intraoperative complication occurred in this series, which consisted in both right ureteral and bladder injuries. Early postoperative complications were represented by urinary bladder dysfunction (33.33%), symptomatic pelvic lymphocele (11.1%), peritonitis (5.5%), and wound infection (5.5%). Late postoperative complications included cervical stenosis (5.5%), amenorrhea (11.1%), and pelvic abscess (5.5%). Four out of the 18 patients were operated on during pregnancy between 14 and 20 weeks; 2 of them gave birth at term, 2 of them aborted shortly after the surgery. Two vaginal recurrences were recorded; both were managed by hysterectomy, partial colpectomy and adjuvant chemoradiotherapy. At this moment, all patients are alive with no evidence of disease and 3 of them managed to conceive. In conclusion, ART should be recommended as a fertility-preserving procedure for women in their reproductive age. In selected cases, ART can be performed during pregnancy with encouraging results.

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.

The Double Life-Saving Approach of Abdominal Radical Trachelectomy during Pregnancy for Early-Stage Cervical Cancer-An Overview of the Literature and Our Institutional Experience.

(1) Background: Cervical cancer is the most common type of cancer encountered during pregnancy, with a frequency of 0.8-1.5 cases per 10,000 births. It is a dire condition endangering patients' lives and pregnancy outcomes, and jeopardizing their fertility. However, there is a lack of current evidence and consensus regarding a standard surgical technique for pregnant patients who suffer from this condition during pregnancy. The study aims to comprehensively update all published data, evaluating the obstetrical and oncological results of pregnant patients who underwent abdominal radical trachelectomy during early stages of cervical cancer. (2) Methods: A literature search on the Medline, PubMed, and Google Scholar databases was performed, including all articles in question up to July 2020. This study presents an overview of the literature and our institutional experience. (3) Results: A total of 25 cases of abdominal radical trachelectomy were performed during pregnancy for early cervical cancer, including the five cases managed by the authors. Of these, 81% (19 patients) gave birth to live newborns through elective C-section, and 19% (6 patients) experienced miscarriage shortly after the procedure. None of the 25 patients (100%) reported disease recurrence. (4) Conclusions: The results of the current study were satisfactory. However, abdominal radical trachelectomy does not represent the current standard of care for cervical cancer during pregnancy, but it could play an important role if more evidence on its effectiveness will be provided.

Ovarian Damage after Laparoscopic Cystectomy for Endometrioma.

INTRODUCTION: Despite extensive research endometriosis is an area with important controversies. The European Society of Human Reproduction and Embriology issued in 2014 the last Guideline for endometriosis management including the statement that among 83 recommendations in 32 cases the best available evidence was only based on good clinical practice, further research being necessary to solve the lack of evidence in this pathology. The prevalence of endometriosis is unknown in Romania but in the medical literature estimates range from 2 to 10% of women of reproductive age, to 50% of infertile women, worldwide. Ovarian endometrioma prevalence goes up to 44%. A Cochrane review published in 2008 by Hart et al. concluded that excisional surgery of ovarian endometriosis results in a more favorable outcome compared to drainage and ablation with regard to recurrence, pain symptoms and subsequent spontaneous pregnancy in subfertilewomen- so the gold standard was set. But several authors revealed that ovarian tissue was inadvertently excised together with the cyst wall and endometrioma cystectomy is associated with a significant decrease in residual ovarian volume that may result in diminished ovarian reserve and function. The aim of our retrospective study was to evaluate whether or not ovarian parenchyma is inadvertently removed during laparoscopic surgery for endometrioma in a Romanian academic center. MATERIAL AND METHOD: We performed a retrospective study including women having undergone endometrioma excision, between January 2009 to June 2014 in the Department of Gynecology and Obstetrics of Targu-Mures University Hospital. Histological specimens of excised endometriomas were reviewed by different pathologists, who carried out serial microscopic sections according to pathology protocol for diagnosis of ovarian mass but not specific for the ovarian parenchyma removed with the cyst. RESULTS: Among 202 endometriomas, drainage and ablation was done in 60 cases and excisional surgery in the remaining 152 cases. Ovarian parenchyma was found in 40% of cases of endometrioma cystectomy. DISCUSSION: We observed that endometrioma cystectomy leads to ovarian tissue removal in an important number of cases. Furthermore, at the time of surgery the amount of ovarian parenchyma loss may increases proportionally with increases in cyst diameter and patient age. Considering that most of the woman in our series were infertile and because of data from series using plasma energy, a shift in the endometrioma treatment paradigm is likely to occur.

Correlates of cognitive impairment in first episode schizophrenia: the EUFEST study.

BACKGROUND: Profile and correlates of cognitive deficits in first episode (FE) schizophrenia patients are still debated. The present study is aimed to clarify in a large sample of FE patients the extent of impairment in key cognitive domains and its relationships with demographic and clinical variables. METHOD: The European First Episode Schizophrenia Trial collected demographic, clinical and neurocognitive baseline data in 498 FE patients with minimal or no prior exposure to antipsychotics. Two-hundred-twenty healthy subjects (HS) were also evaluated. Neurocognitive assessment included the Rey Auditory Verbal Learning Test; Trail Making A and B, Purdue Pegboard and Digit-Symbol Coding. RESULTS: Patients performed worse than HS on all tests (effect sizes from -0.88 to -1.73). Correlations with psychopathological dimensions were weak and involved reality distortion and disorganization. The duration of untreated psychosis (DUP) was not associated with cognitive impairment. Subjects living alone had a better neurocognitive performance, while the occupation status did not reveal any association with cognition. CONCLUSIONS: A moderate/severe impairment of processing speed, motor dexterity, verbal memory and cognitive flexibility was found in the largest sample of FE patients analyzed so far. The impairment was largely independent from psychopathology and not associated with DUP.

Management of patients presenting with acute psychotic episodes of schizophrenia.

The initial management of patients with schizophrenia presenting to psychiatric emergency departments with an acute psychotic episode requires rapid decisions to be made by physicians concerning the treatment of individuals who are likely to be relatively uncooperative, agitated and lacking insight. The treatment decision must be adapted to the individual characteristics and needs of each patient. This article reviews the issues from the perspective of the initial management of acute psychosis as it is currently practised in Europe, and discusses the pragmatic implications for initial treatment decisions and the elaboration of a long-term treatment plan. Initially, administration of antipsychotics to control psychotic symptoms and benzodiazepines to control agitation represents the cornerstone of treatment. Oral medication is preferable to injectable forms wherever possible, and atypical antipsychotics are to be preferred over conventional agents because of their lower risk of extrapyramidal adverse effects, which are a major determinant of poor adherence to treatment. Whatever antipsychotic is chosen by the physician during the initial period, it is likely that it will need to be continued for many years, and it is thus important to take into account the long-term safety profile of the drug chosen, particularly in relation to extrapyramidal adverse effects, metabolic complications and quality of life. Building a therapeutic alliance with the patient and his/her family or carers is an important element that should be included in the initial management of psychosis. The long-term goal should be to minimize the risk of psychotic relapse through adequate treatment adherence.

Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial.

BACKGROUND: Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. METHODS: We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. FINDINGS: The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0.37, [95% CI 0.24-0.57]), olanzapine (HR 0.28 [0.18-0.43]), quetiapine (HR 0.52 [0.35-0.76]), and ziprasidone (HR 0.51 [0.32-0.81]). However, symptom reductions were virtually the same in all the groups, at around 60%. INTERPRETATION: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement.