Successful Pre-Treatment Ovarian Fresh Tissue Transplantation in a Cervical Cancer Patient Undergoing Radiation Therapy: A Case Report.

Cervical cancer is one of the most frequent gynecological malignancies in Brazil, and most of the patients require pelvic radiotherapy as part of oncological treatment. Pelvic radiotherapy induces ovarian premature insufficiency in pre-menopausal women. This condition impacts the life quality and increases the risk of osteoporosis, obesity, cardiovascular, and neurodegenerative diseases in the middle and long term. Most of these patients have no access to hormonal replacement therapy. Techniques such as ovarian transposition have questionable results when aiming to preserve ovarian function. In this context, a promising alternative is the implantation of fresh ovarian tissue, outside the radiotherapy field, in the abdominal cavity (orthotopic implantation) or in other sites such as the forearm, breast, or subcutaneous tissue (heterotopic implantation). Here we report a successful case of autologous implantation of fresh ovarian tissue in the inner thigh of a young patient with advanced cervical cancer, who was a candidate for concurrent chemoradiotherapy.

Mucinous Cystadenoma Arising in a Uterine Isthmocele: A Case Report.

Isthmocele is a discontinuation of the myometrium at the uterine scar site in a patient with a previous cesarian section (CS). The cause of isthmocele appears to be multifactorial. Poor surgical technique, low incision location, uterine retroflection, obesity, smoking, inadequate healing of scars, and maternal age are possible related factors. Most patients with this condition are asymptomatic. However, women can present with postmenstrual bleeding, pelvic pain, subfertility, dysmenorrhea, infertility, and scar abscess. Brazil has one of the world's highest cesarean section rates. One of the consequences of the rising rate of CS is the isthmocele, an emerging female health problem. Here we report a case of mucinous cystadenoma arising in a uterine isthmocele, a complication, as far as we could investigate, not yet described in the literature.

Istmocele é a descontinuidade do miométrio no local da cicatriz uterina em paciente com cesariana anterior. A causa da istmocele parece ser multifatorial. Má técnica cirúrgica, baixa localização da incisão, retroflexão uterina, obesidade, tabagismo, cicatrização inadequada de cicatrizes e idade materna são possíveis fatores relacionados. A maioria dos pacientes com esta condição é assintomática. No entanto, as mulheres podem apresentar sangramento pós-menstrual, dor pélvica, subfertilidade, dismenorreia, infertilidade e abscesso cicatricial. O Brasil tem uma das maiores taxas de cesariana do mundo. Uma das consequências da taxa crescente de cesarianas é a istmocele, um problema emergente de saúde feminina. Aqui relatamos um caso de cistoadenoma mucinoso originado em uma istmocele uterina, uma complicação ainda não descrita, até onde pudemos investigar.

Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status.

DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid histology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less ≥50% myometrial invasion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myometrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.

Gemcitabine-Induced Radiation Recall Phenomenon in Cervical Cancer: A Case Report.

The radiation recall phenomenon is a rare, massive inflammatory reaction induced by some chemotherapeutic agents in previously irradiated areas. When it occurs in the pelvis it looks like a recurrence. Recognizing this phenomenon is paramount to avoiding unnecessary surgical intervention and complications. Symptoms manifest as dermatitis, mucositis, myositis, esophagitis, colitis, proctitis, and pneumonitis in areas within the irradiation field. Most patients respond to clinical treatment with corticosteroids. Here, we describe a 47-year-old patient with cervical carcinoma, FIGO stage IIB, submitted to external beam radiotherapy and concomitant chemotherapy with cisplatin (40 mg/m2 weekly), followed by intracavitary brachytherapy. One month after the end of radiotherapy and chemotherapy, the patient underwent laparoscopic completion hysterectomy plus bilateral salpingo-oophorectomy, followed by three cycles of cisplatin 50 mg/m2 D1 and gemcitabine 1,000 mg/m2 D1 and D8. Four months after the surgery, she presented with a suspicious mass in the vaginal dome that proved to be an exuberant inflammatory reaction that regressed after treatment with corticosteroids.

Mucinous Cystadenoma Arising in a Uterine Isthmocele: A Case Report / Cistadenoma mucinoso surgindo em istmocele uterina: relato de caso

Abstract Isthmocele is a discontinuation of the myometrium at the uterine scar site in a patient with a previous cesarian section (CS). The cause of isthmocele appears to be multifactorial. Poor surgical technique, low incision location, uterine retroflection, obesity, smoking, inadequate healing of scars, and maternal age are possible related factors. Most patients with this condition are asymptomatic. However, women can present with postmenstrual bleeding, pelvic pain, subfertility, dysmenorrhea, infertility, and scar abscess. Brazil has one of the world s highest cesarean section rates. One of the consequences of the rising rate of CS is the isthmocele, an emerging female health problem. Here we report a case of mucinous cystadenoma arising in a uterine isthmocele, a complication, as far as we could investigate, not yet described in the literature.

Resumo Istmocele é a descontinuidade do miométrio no local da cicatriz uterina em paciente com cesariana anterior. A causa da istmocele parece ser multifatorial. Má técnica cirúrgica, baixa localização da incisão, retroflexão uterina, obesidade, tabagismo, cicatrização inadequada de cicatrizes e idade materna são possíveis fatores relacionados. A maioria dos pacientes com esta condição é assintomática. No entanto, as mulheres podem apresentar sangramento pós-menstrual, dor pélvica, subfertilidade, dismenorreia, infertilidade e abscesso cicatricial. O Brasil tem uma das maiores taxas de cesariana do mundo. Uma das consequências da taxa crescente de cesarianas é a istmocele, um problema emergente de saúde feminina. Aqui relatamos um caso de cistoadenoma mucinoso originado em uma istmocele uterina, uma complicação ainda não descrita, até onde pudemos investigar.

Preservação da fertilidade em pacientes com câncer ginecológico / Fertility preservation in gynecologic cancer patients

CONTEXTO CLÍNICO O câncer ginecológico afeta diretamente a fertilidade, pois o tratamento consiste na remoção cirúrgica do sistema reprodutor e/ou na sua exposição a agentes gonadotóxicos. Entretanto, pacientes em estádios iniciais e que estejam dentro de critérios estabelecidos podem ser tratadas com cirurgias conservadoras da fertilidade, com resultados oncológicos equivalentes aos dos tratamentos tradicionais. As técnicas de preservação da fertilidade, como criopreservação de oócitos, embriões e tecido ovariano, também podem ser oferecidas em algumas situações. A American Society of Clinical Oncology (ASCO) publicou recomendações sobre a preservação de fertilidade, com o objetivo de aumentar a conscientização sobre o tema, e, juntamente com a American Society for Reproductive Medicine (ASRM), recomenda que pacientes em idade fértil com câncer passem por aconselhamento reprodutivo. Essas pacientes apresentam menores taxas de arrependimento, mesmo quando optam por desistir do tratamento conservador. O interesse na preservação da fertilidade aumentou nas últimas décadas, tanto pelo fato de as mulheres postergarem a gestação como pelo aumento da incidência de câncer em jovens. A taxa de incidência de todos os cânceres aumentou 29% entre 1973 e 2015 em adolescentes e adultos jovens de ambos os sexos. O câncer de colo uterino, em mulheres de 20-29 anos, aumentou anualmente em uma média de 10,3% entre 2000 e 2009. A omissão em orientar pacientes com câncer sobre as possibilidades de preservação da fertilidade pode gerar questionamentos futuros; em alguns países. isso já se configura má prática médica.

A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer.

BACKGROUND: The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer. METHODS: A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes. RESULTS: The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%. CONCLUSION: We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.

Everolimus plus anastrozole for female adnexal tumor of probable Wolffian origin (FATWO) with STK11 mutation.

Female adnexal tumor of probable Wolffian origin (FATWO) are a rare type of cancer that originates from Wolffian duct remnants. Due to its rarity, no standard systemic treatment is established for cases of recurrent or metastatic disease. Previous literature reported the use of platinum-based chemotherapy and c-Kit tyrosine kinase inhibitors for FATWO cases with c-Kit positive expression. Currently, however, the broader availability of next-generation sequencing (NGS) tests allows a better molecular characterization of rare cancer such as FATWO and a possibility for the use of personalized, targeted therapy. Previous case series that performed NGS for FATWO patients described the presence of STK11 mutations in a considerable number of cases, representing a potential target in this population. To our knowledge, we describe here the first case report of a patient with FATWO and STK11 mutation exhibiting a considerable and durable response after treatment with an mTOR inhibitor plus endocrine therapy.

Dysregulation of Transcription Factor Networks Unveils Different Pathways in Human Papillomavirus 16-Positive Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the most common histological types of cervical cancer (CC). The worse prognosis of ADC cases highlights the need for better molecular characterization regarding differences between these CC types. RNA-Seq analysis of seven SCC and three ADC human papillomavirus 16-positive samples and the comparison with public data from non-tumoral human papillomavirus-negative cervical tissue samples revealed pathways exclusive to each histological type, such as the epithelial maintenance in SCC and the maturity-onset diabetes of the young (MODY) pathway in ADC. The transcriptional regulatory network analysis of cervical SCC samples unveiled a set of six transcription factor (TF) genes with the potential to positively regulate long non-coding RNA genes DSG1-AS1, CALML3-AS1, IGFL2-AS1, and TINCR. Additional analysis revealed a set of MODY TFs regulated in the sequence predicted to be repressed by miR-96-5p or miR-28-3p in ADC. These microRNAs were previously described to target LINC02381, which was predicted to be positively regulated by two MODY TFs upregulated in cervical ADC. Therefore, we hypothesize LINC02381 might act by decreasing the levels of miR-96-5p and miR-28-3p, promoting the MODY activation in cervical ADC. The novel TF networks here described should be explored for the development of more efficient diagnostic tools.