RESUMEN
Pain during sexual intercourse, also called dyspareunia, affects most women after treatment for gynecological cancer. Previous work adopted a biomedical approach to depict dyspareunia in this population, which provided a narrow perspective of this condition. Taking into account women's experiences of dyspareunia and the factors influencing their care-seeking behaviors would provide insight to improve care in the context of gynecological cancer. The aim of this study was to describe gynecological cancer survivors' experiences of dyspareunia and factors influencing care-seeking behavior. A qualitative study was performed with 28 gynecological cancer survivors with dyspareunia. Individual telephone interviews were conducted based on the Common-Sense Model of Self-Regulation. Interviews were recorded and transcribed for analysis using the interpretative description framework. Concerning their experience, participants reported the oncological treatments as the primary cause of dyspareunia. Loss of libido, lower vaginal lubrication, and smaller vaginal cavity were described as being linked with dyspareunia. Women explained how dyspareunia and these changes had led them to engage less in, and even interrupt, sexual activity. They expressed that they were distressed, felt less of a woman, and experienced low control and/or self-efficacy. Regarding the factors influencing women's care-seeking behaviors, participants emphasized that they were provided with insufficient information and support. Balancing priorities, denial or reluctance, misbeliefs, resignation and acceptance, and negative emotions were reported as barriers, whereas acknowledgement of sexual dysfunction, desire for improvement, awareness of treatment possibilities, willingness to undertake treatment and treatment acceptability were reported as facilitators to seeking care. Findings suggest that dyspareunia is a complex and impactful condition after gynecological cancer. While this study highlights the importance of alleviating the burden of sexual dysfunction in cancer survivors, it identified factors that should be considered in the provision of services to improve care.
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Supervivientes de Cáncer , Dispareunia , Neoplasias , Disfunciones Sexuales Fisiológicas , Femenino , Humanos , Dispareunia/terapia , Dispareunia/psicología , Conducta Sexual/psicología , Coito , Aceptación de la Atención de Salud/psicología , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Fisiológicas/terapiaRESUMEN
BACKGROUND: Ovarian cancer is rare during pregnancy. For patients beyond 20 weeks of gestation who choose to continue the pregnancy, neoadjuvant chemotherapy may be initiated, followed by interval debulking surgery. Hyperthermic intraperitoneal chemotherapy (HIPEC) may be used with interval debulking surgery for stage III epithelial ovarian cancer, but data are lacking on its administration in the peripartum period. CASE: We illustrate the case of a 40-year-old patient diagnosed with stage III epithelial ovarian cancer at 27 weeks of gestation who underwent neoadjuvant chemotherapy followed by cesarean delivery at term along with interval debulking surgery and HIPEC. The intervention was well tolerated and resulted in the birth of a healthy neonate. The postoperative period was unremarkable, and the patient is disease-free after 22-months of follow-up. CONCLUSION: We demonstrate the feasibility of peripartum HIPEC. Optimal oncologic care should not be jeopardized by the peripartum state of an otherwise healthy patient.
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Hipertermia Inducida , Neoplasias Ováricas , Femenino , Recién Nacido , Embarazo , Humanos , Adulto , Quimioterapia Intraperitoneal Hipertérmica , Carcinoma Epitelial de Ovario/cirugía , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida/efectos adversos , Hipertermia Inducida/métodos , Neoplasias Ováricas/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
INTRODUCTION AND HYPOTHESIS: Multimodal pelvic floor physical therapy (PFPT) is recommended after gynecological malignancies to treat dyspareunia. However, data to strongly support its implementation in the cancer care continuum are lacking. The aim of this study was to explore the views and experiences of gynecological cancer survivors with dyspareunia regarding the acceptability of multimodal PFPT. METHODS: This qualitative study was conducted with the participants (n = 28) of a study investigating a 12-week multimodal PFPT treatment. Individual semi-structured telephone interviews served to collect qualitative data pertaining to women's views and experiences of the treatment they received. Interviews were recorded and transcribed for analysis using the interpretative description framework. RESULTS: Our cohort described the appropriateness of the treatment in terms of modalities, physical therapist, care delivery, and intensity (Theme 1). While the intensity was reported as demanding by a few, all participants stressed that it was relevant to see significant improvements (Theme 2). In addition to the treatment characteristics and women's beliefs and attitudes, noticing the treatment effects motivated their participation (Theme 2). Women expressed being highly satisfied with the treatment based on their positive experiences and the balance between their efforts and the results they obtained (Theme 3). As a result, they all recommended this treatment (Theme 3). CONCLUSIONS: This is the first study to examine the acceptability of multimodal PFPT in the context of gynecological malignancies. This treatment was found acceptable and can be offered to gynecological cancer survivors.
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Dispareunia , Neoplasias de los Genitales Femeninos , Trastornos del Suelo Pélvico , Femenino , Humanos , Dispareunia/etiología , Dispareunia/terapia , Diafragma Pélvico , Neoplasias de los Genitales Femeninos/complicaciones , Modalidades de Fisioterapia , Trastornos del Suelo Pélvico/complicaciones , Trastornos del Suelo Pélvico/terapia , Investigación CualitativaRESUMEN
Human papillomavirus-associated vulvar intraepithelial neoplasia (high-grade squamous intraepithelial neoplasia [HSIL] or VIN of usual type) is a lesion characterized by atypia extending from the basal layer to the upper epidermis. There are only rare reports of vulvar intraepithelial morphology exhibiting a pagetoid pattern of intraepithelial dissemination. We herein report two cases of vulvar HSIL in which a pagetoid pattern of spread and a largely uninvolved basal layer represented a diagnostic pitfall for extramammary Paget disease. Nuclear atypia reminiscent of HSIL in addition to expression of p16, KRT5/6, and p40 were however in favor of pagetoid HSIL. Although there is morphological and immunohistochemical overlap between these two entities, an accurate diagnosis is important, since an erroneous diagnosis of vulvar extramammary Paget disease may lead to an extensive workup comprising radiological imaging, colonoscopy, and cystoscopy.
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Carcinoma in Situ , Carcinoma de Células Escamosas , Enfermedad de Paget Extramamaria , Neoplasias de la Vulva , Femenino , Humanos , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/cirugía , Vulva/patología , Neoplasias de la Vulva/patología , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Epidermis/patologíaRESUMEN
BACKGROUND: A large proportion of gynecological cancer survivors suffer from pain during sexual intercourse, also known as dyspareunia. Following a multimodal pelvic floor physical therapy (PFPT) treatment, a reduction in pain and improvement in psychosexual outcomes were found in the short term, but no study thus far has examined whether these changes are sustained over time. PURPOSE: To examine the improvements in pain, sexual functioning, sexual distress, body image concerns, pain anxiety, pain catastrophizing, painful intercourse self-efficacy, depressive symptoms and pelvic floor disorder symptoms in gynecological cancer survivors with dyspareunia after PFPT, and to explore women's perceptions of treatment effects at one-year follow-up. METHODS: This mixed-method study included 31 gynecological cancer survivors affected by dyspareunia. The women completed a 12-week PFPT treatment comprising education, manual therapy and pelvic floor muscle exercises. Quantitative data were collected using validated questionnaires at baseline, post-treatment and one-year follow-up. As for qualitative data, semi-structured interviews were conducted at one-year follow-up to better understand women's perception and experience of treatment effects. RESULTS: Significant improvements were found from baseline to one-year follow-up on all quantitative outcomes (P ≤ 0.028). Moreover, no changes were found from post-treatment to one-year follow-up, supporting that the improvements were sustained at follow-up. Qualitative data highlighted that reduction in pain, improvement in sexual functioning and reduction in urinary symptoms were the most meaningful effects perceived by participants. Women expressed that these effects resulted from positive biological, psychological and social changes attributable to multimodal PFPT. Adherence was also perceived to influence treatment outcomes. CONCLUSIONS: Findings suggest that the short-term improvements following multimodal PFPT are sustained and meaningful for gynecological cancer survivors with dyspareunia one year after treatment.
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Supervivientes de Cáncer/psicología , Dispareunia , Terapia por Ejercicio , Neoplasias de los Genitales Femeninos , Trastornos del Suelo Pélvico , Adulto , Anciano , Dispareunia/etiología , Dispareunia/fisiopatología , Dispareunia/psicología , Dispareunia/terapia , Femenino , Estudios de Seguimiento , Neoplasias de los Genitales Femeninos/fisiopatología , Neoplasias de los Genitales Femeninos/psicología , Neoplasias de los Genitales Femeninos/terapia , Humanos , Persona de Mediana Edad , Diafragma Pélvico , Trastornos del Suelo Pélvico/etiología , Trastornos del Suelo Pélvico/fisiopatología , Trastornos del Suelo Pélvico/psicología , Trastornos del Suelo Pélvico/terapiaRESUMEN
OBJECTIVE: To investigate the changes in pelvic floor morphometry and muscle function after multimodal pelvic floor physiotherapy treatment in gynaecological cancer survivors suffering from painful intercourse (dyspareunia). DESIGN: Prospective interventional study. SETTING: Three university hospitals. PARTICIPANTS: Thirty-one gynaecological cancer survivors with dyspareunia. INTERVENTION: The treatment consisted of 12 weekly sessions of physiotherapy combining education, pelvic floor muscle exercises with biofeedback, manual therapy and home exercises. MAIN OUTCOME MEASURES: Women were assessed at baseline and post-treatment. Pelvic floor morphometry was evaluated at rest and on maximal contraction by measuring bladder neck position, anorectal and levator plate angles as well as levator hiatal dimensions with three-dimensional/four-dimensional transperineal ultrasound imaging. Pelvic floor muscle function was evaluated by measuring passive forces (muscle tone measure), flexibility, stiffness, strength, coordination and endurance with an intra-vaginal dynamometric speculum. RESULTS: Significant changes in pelvic floor morphometry and muscle function were found post-treatment. The parameters assessing the changes from rest to maximal contraction significantly improved (e.g., mean change of levator hiatal area narrowing 14%, 95% CI 11-18, Cohen's d effect size 1.48)), supporting the hypothesis of decreased muscle tone and improved muscle contractility following treatment. Women also presented with a significant decrease in tone (mean change -0.4N, 95% CI -0.7 to -0.1, Cohen's d effect size 0.57) and stiffness (mean change -0.1N/mm, 95% CI -0.2 to -0.1, Cohen's d effect size 0.59), as well as significant improvements in flexibility (mean change 9.0mm, 95% CI 5.8-12.2, Cohen's d effect size 1.08), coordination (mean change 3 rapid contractions, 95% CI 2-4, Cohen's d effect size 0.85) and endurance (mean change 683%*s, 95% CI 388-978, Cohen's d effect size 0.90). CONCLUSION: Our findings suggest significant improvements in pelvic floor morphometry and muscle function after a multimodal physiotherapy treatment in gynaecological cancer survivors with dyspareunia. These effects may represent key treatment mechanisms to reduce dyspareunia, supporting the rationale for multimodal physiotherapy in this population. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): NCT03935698.
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Supervivientes de Cáncer , Dispareunia , Neoplasias , Dispareunia/terapia , Femenino , Humanos , Contracción Muscular/fisiología , Diafragma Pélvico/diagnóstico por imagen , Modalidades de Fisioterapia , Estudios Prospectivos , Ultrasonografía/métodosRESUMEN
AIMS: We aimed to characterise a large cohort of non-invasive, human papillomavirus (HPV) and p53-independent verruciform lesions, such as 'vulvar acanthosis with altered differentiation' (VAAD), 'differentiated exophytic vulvar intra-epithelial lesion' (DEVIL) and 'verruciform lichen simplex chronicus' (vLSC). METHODS AND RESULTS: From January 2008 to December 2020 we retrospectively identified 36 eligible patients with verruciform non-invasive lesions (n = 36) and collected clinical, histological and follow-up parameters. Verruciform non-invasive lesions occurred at a median age of 71 years, with a median follow-up of 33.5 months. Clinically, pruritus was only reported in patients with VAAD (n = 3, 21%). Lesion colour was significantly different across categories (P = 0.028). Apart from the histopathological criteria already known to distinguish these entities (hypogranulosis, epithelial pallor and low-magnification architecture), no other significant criteria were discovered and significant overlap was observed, particularly between VAAD and DEVIL. Patients with vLSC trended towards longer survival without recurrence compared to VAAD and DEVIL (P = 0.082), but showed comparable invasion-free survival interval (P = 0.782). Squamous cell carcinomas (SCC) associated with either VAAD, DEVIL or vLSC displayed similar clinical, histopathological and biological parameters. In non-invasive precursor lesions, stromal oedema was associated with invasion (P = 0.015) and remained so upon Cox regression analysis (P = 0.009). CONCLUSION: Our study of HPV and p53 independent non-invasive verruciform lesions of the vulva highlights significant clinical, histopathological and biological overlap between VAAD, DEVIL and vLSC, suggesting that these pre-invasive lesions should be viewed as a spectrum. We also show that stromal features such as oedema might play an import role in progression to invasion.
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Carcinoma in Situ/patología , Lesiones Precancerosas/patología , Neoplasias de la Vulva/patología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Proteína p53 Supresora de TumorRESUMEN
BACKGROUND: Dyspareunia affects most women after treatment for gynecologic malignancies. However, to date, evidence-based interventions remain limited and no study has examined the effects of multimodal physical therapy on psychosexual outcomes in these patients. AIM: To assess the effects of multimodal physical therapy on psychosexual outcomes including sexual distress, body image concerns, pain anxiety, pain catastrophizing, pain self-efficacy and depressive symptoms in women with dyspareunia after treatment for gynecologic malignancies. METHODS: Thirty-one gynecologic cancer survivors with dyspareunia enrolled in this prospective single-arm interventional study. The participants undertook 12 weekly sessions of physical therapy incorporating education, pelvic floor muscle exercises with biofeedback, manual therapy and home exercises. Outcome measures were evaluated pre- and post-treatment. Paired t-tests were conducted to investigate the changes from pre-treatment (P-value Ë 0.05) while effect sizes (Cohen's d) were calculated to measure the magnitude of the change. MAIN OUTCOME MEASURES: Sexual distress (Female Sexual Distress Scale-Revised), body image concerns (Body Image Scale), pain anxiety (Pain Anxiety Symptoms Scale), pain catastrophizing (Pain Catastrophizing Scale), pain self-efficacy (Painful Intercourse Self-Efficacy Scale) and depressive symptoms (Beck Depression Inventory-II). RESULTS: Significant changes were found from pre- to post-treatment for all psychosexual outcomes. Women reported reductions in sexual distress (P Ë 0.001, d = 1.108), body image concerns (P Ë 0.001, d = 0.829), pain anxiety (P Ë 0.001, d = 0.980), pain catastrophizing (P Ë 0.001, d = 0.968) and depression symptoms (P = 0.002, d = 0.636) with an increase in pain self-efficacy (P Ë 0.001, d ≥ 0.938) following the intervention. CLINICAL IMPLICATIONS: The results suggest that multimodal physical therapy significantly improves sexual distress, body image concerns, pain anxiety, pain catastrophizing, pain self-efficacy and depressive symptoms in our sample of women with dyspareunia after treatment for gynecologic malignancies. The medium to large effect sizes obtained with the high proportion of women presenting meaningful changes according to the known minimal clinically important difference or clinical cut-off underlines the significance of these effects. STRENGTHS & LIMITATIONS: The current study used validated questionnaires to assess the psychosexual outcomes of a well-designed physical therapy intervention using multiple modalities to address the multifaceted aspect of dyspareunia in cancer survivors. This study did not include a control group, which may limit drawing definitive conclusions. CONCLUSION: Findings showed that multimodal physical therapy yielded significant improvements in psychosexual outcomes in gynecologic cancer survivors with dyspareunia. A randomized controlled trial is indicated to confirm these results. Cyr M-P, Dumoulin C, Bessette P, et al. A Prospective Single-Arm Study Evaluating the Effects of a Multimodal Physical Therapy Intervention on Psychosexual Outcomes in Women With Dyspareunia After Gynecologic Cancer. J Sex Med 2021;18:946-954.
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Dispareunia , Neoplasias de los Genitales Femeninos , Dispareunia/terapia , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Humanos , Modalidades de Fisioterapia , Estudios Prospectivos , Conducta Sexual , Encuestas y CuestionariosRESUMEN
OBJECTIVE: More than one-half of gynecological cancer survivors are affected by pain during sexual intercourse, also known as dyspareunia. Oncological treatments may result in pelvic floor muscle (PFM) alterations, which are suspected to play a key role in dyspareunia. However, to our knowledge, no study has investigated PFM function and morphometry in this population. The aim of the study was to characterize and compare PFM function and morphometry between gynecological cancer survivors with dyspareunia and asymptomatic women. METHODS: Twenty-four gynecological cancer survivors with dyspareunia and 32 women with a history of total hysterectomy but without pelvic pain (asymptomatic women) participated in this comparative cross-sectional study. PFM passive forces (tone), flexibility, stiffness, maximal strength, coordination, and endurance were assessed with an intra-vaginal dynamometric speculum. Bladder neck position, levator plate angle, anorectal angle, and levator hiatal dimensions were measured at rest and on maximal contraction with 3D/4D transperineal ultrasound imaging. RESULTS: Compared with asymptomatic women, gynecological cancer survivors showed heightened PFM tone, lower flexibility, higher stiffness, and lower coordination and endurance. At rest, they had a smaller anorectal angle and smaller levator hiatal dimensions, indicating heightened PFM tone. They also presented fewer changes from rest to maximal contraction for anorectal angle and levator hiatal dimensions, suggesting an elevated tone or altered contractile properties. CONCLUSIONS: Gynecological cancer survivors with dyspareunia present with altered PFM function and morphometry. This research therefore provides a better understanding of the underlying mechanisms of dyspareunia in cancer survivors. IMPACT: Our study confirms alterations in PFM function and morphometry in gynecological cancer survivors with dyspareunia. These findings support the rationale for developing and assessing the efficacy of physical therapy targeting PFM alterations in this population.
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Dispareunia/fisiopatología , Neoplasias de los Genitales Femeninos/complicaciones , Trastornos del Suelo Pélvico/fisiopatología , Anciano , Supervivientes de Cáncer , Estudios Transversales , Dispareunia/diagnóstico por imagen , Dispareunia/etiología , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Persona de Mediana Edad , Trastornos del Suelo Pélvico/diagnóstico por imagen , Trastornos del Suelo Pélvico/etiología , Encuestas y Cuestionarios , UltrasonografíaRESUMEN
OBJECTIVES: Painful sexual intercourse (dyspareunia) is a distressing condition affecting a large proportion of gynecological cancer survivors, yet treatments remain limited and poorly studied. This multicenter prospective interventional study examined the feasibility, acceptability and effects of multimodal pelvic floor physical therapy in gynecological cancer survivors with dyspareunia. METHODS: Thirty-one endometrial and cervical cancer survivors with dyspareunia participated in 12 weekly 60-min physical therapy sessions combining education, manual therapy, pelvic floor muscle exercises using biofeedback and home exercises, which included the use of a dilator. The adherence rate to home exercises (≥80%), the attendance rate at physical therapy sessions (≥80% of participants attending ≥10 sessions) and the dropout rate (Ë15%) served as feasibility and acceptability outcomes and benchmarks. Pain intensity, pain quality, sexual function, pelvic floor dysfunction symptoms and quality of life were measured at baseline and post-treatment. Treatment satisfaction and participants' perceived improvement were also assessed. RESULTS: The adherence rate was 88% (SD 10), 29/31 (94%) women attended ≥10 treatment sessions, and the dropout rate was 3%. Moreover, women experienced significant improvements in all outcomes after the intervention (p ≤ 0.044). They also reported being highly satisfied with the treatment (9.3/10 (SD 1.2)), and 90% of them were very much or much improved. CONCLUSIONS: Our findings support the feasibility and acceptability of multimodal pelvic floor physical therapy for gynecological cancer survivors with dyspareunia. The intervention also led to significant improvements in pain, sexual function, pelvic floor dysfunction symptoms and quality of life. A randomized controlled trial is needed to confirm these results.
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Supervivientes de Cáncer/estadística & datos numéricos , Dispareunia/rehabilitación , Terapia por Ejercicio/métodos , Neoplasias de los Genitales Femeninos/terapia , Diafragma Pélvico/fisiopatología , Cuidados Posteriores/métodos , Anciano , Supervivientes de Cáncer/psicología , Coito/fisiología , Coito/psicología , Terapia Combinada , Dispareunia/diagnóstico , Dispareunia/etiología , Dispareunia/fisiopatología , Terapia por Ejercicio/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/mortalidad , Humanos , Persona de Mediana Edad , Dimensión del Dolor/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Proyectos Piloto , Estudios Prospectivos , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVES: Mismatch repair deficiency is observed in 25%-30% of all endometrial cancers. This can be detected by the absence of mismatch repair protein staining on immunohistochemistry, and is used as a screen for Lynch syndrome. Only 10% of women with mismatch repair deficiency have Lynch syndrome, but mismatch repair deficiency may still have prognostic significance. The objective of this study was to compare clinical outcomes between mismatch repair-deficient and mismatch repair-proficient low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2). METHODS: This was a retrospective population-based cohort study of all low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2) from the Vancouver Coastal Health Authority region from February 2011 to January 2016 that were assessed for mismatch repair deficiency. Any other histology, stage, or grade was excluded from the study. Primary outcome measures were progression-free survival and overall survival calculated using Kaplan-Meier method and log-rank tests. Cox proportional hazards model estimated the association between mismatch repair deficiency and recurrence and death after adjustment for covariates, expressed as hazard ratios (HRs). Secondary outcome measures were recurrence rates expressed per 100 person-years (p100py). RESULTS: There were 475 patients diagnosed with low-risk endometrioid endometrial cancer, including 131 with mismatch repair-deficient (27.6%) and 344 with mismatch repair-proficient (72.4%) tumors. Women with mismatch repair-deficient tumors had worse progression-free survival (24 months; p=0.0082) and higher recurrence rates (3.56 p100py) compared with those with mismatch repair-proficient tumors (27 months; 1.21 p100py, p=0.04). The absolute number of recurrences was overall low. There were 11 recurrences out of 131 mismatch repair-deficient cases (8.4%) and 14 out of 344 mismatch repair proficient cases (4.1%). After adjustment for age, lymphovascular space invasion status, adjuvant therapy, and post-operative grade, mismatch repair-deficient status remained associated with a higher risk of recurrence (HR 3.56, 95% CI 2.01 to 5.95). There was no significant difference in overall survival between mismatch repair groups (mismatch repair-proficient group 27.5 months vs 25.0 months in the deficient group) (HR 1.23, 95% CI 0.49 to 3.10). CONCLUSION: In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, mismatch repair deficiency is associated with a higher recurrence rate than mismatch repair proficiency after adjustment for covariates, implying that mismatch repair deficiency reflects a different biology in endometrial cancer.
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Carcinoma Endometrioide/etiología , Reparación de la Incompatibilidad de ADN , Neoplasias/etiología , Anciano , Colombia Británica/epidemiología , Carcinoma Endometrioide/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Neoplasias/mortalidad , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: Our aim was to characterize the pathological, molecular and clinical outcomes of clear cell carcinoma of the endometrium (CCC). METHODS: CCC underwent ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification identifying four molecular subtypes: i) 'POLEmut' for ECs with pathogenic POLE mutations, ii) 'MMRd', if there is loss of mismatch repair proteins by immunohistochemistry (IHC), iii) 'p53wt' or iv) 'p53abn' based on p53 IHC staining. Clinicopathologic parameters, immune markers (CD3, CD8, CD79a, CD138, PD-1), ER, L1CAM, and outcomes were assessed. RESULTS: 52 CCCs were classified, including 1 (2%) POLEmut, 5 (10%) MMRd, 28 (54%) p53wt and 18 (35%) p53abn. Women with p53abn and p53wt CCCs were older than women with MMRd and POLEmut subtypes. p53wt CCC were distinct from typical p53wt endometrioid carcinomas; more likely to arise in older, thinner women, with advanced stage disease, LVSI and lymph node involvement, and a higher proportion ER negative, L1CAM overexpressing tumors with markedly worse outcomes. High levels of immune infiltrates (TILhigh) were observed in 75% of the CCC cohort. L1CAM overexpression was highest within p53abn and p53wt subtypes of CCC. CONCLUSION: CCC is a heterogeneous disease encompassing all four molecular subtypes and a wide range of clinical outcomes. Outcomes of patients with POLEmut, MMRd and p53abn CCC are not distinguishable from those of other patients with these respective subtypes of EC; p53wt CCC, however, differ from endometrioid p53wt EC in clinical, pathological, molecular features and outcomes. Thus, p53wt CCC of endometrium appear to be a distinct clinicopathological entity within the larger group of p53wt ECs.
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Adenocarcinoma de Células Claras/clasificación , Neoplasias Endometriales/clasificación , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estudios de Cohortes , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
INTRODUCTION: Low risk gestational trophoblastic neoplasia, WHO prognostic score of 0 to 6, is highly curable. There is no consensus on the optimal chemotherapy. Common regimens are q2wk actinomycin-D (ACT-D), weekly intramuscular methotrexate (MTX) or multi-day MTX. Combination MTX/ACT-D is rarely used. METHODS: A four centre, retrospective cohort study was carried out comparing commonly used regimens: weekly MTX, q2weekly ACT-D and q2 weekly MTX and ACT-D. RESULTS: 412 patients - 196 MTX/ACT-D, 107 MTX, 109 ACT-D - were treated between October 1994 and January 2019. Initial regimen failure (secondary to resistance or toxicity) occurred in 37% (MTX), 21% (ACT-D) and 5% (MTX/ACT-D). Relapse after completion of primary therapy (initial plus switch to another therapy if needed) was rare (0-5%). All eventually were cured. Mean number of cycles required to achieve remission were 10.1 (MTX), 7 (ACT-D) and 5.6 (MTX/ACT-D) with corresponding mean treatment durations of 3.12, 2.9 and 2.26 months. Dosage reductions occurred in 3% (MTX), 0% (ACT-D) and 29% (MTX/ACT-D). Higher failure rates occurred with WHO prognostic scores of 5 to 6 and HCG levels ≥10,000. SUMMARY: Initial regimen failure ie the need to switch to an alternative treatment was more common with MTX. ACT-D and MTX/ACT-D were similar within prognostic score 0-4 or HCG < 10,000. ACT-D then appears the better initial choice with its superior convenience. Above these levels primary failure rates are less with MTX/ACT-D, making it a better choice.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Dactinomicina/administración & dosificación , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Metotrexato/administración & dosificación , Adolescente , Adulto , Canadá , Gonadotropina Coriónica/sangre , Estudios de Cohortes , Esquema de Medicación , Femenino , Enfermedad Trofoblástica Gestacional/sangre , Enfermedad Trofoblástica Gestacional/patología , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Mismatch repair (MMR) deficiency occurs in 20-40% of endometrial cancers but its therapeutic implication remains uncertain. Our objective was to compare clinical outcomes after adjuvant therapy between MMR deficient and proficient endometrial cancers from a population-based study. METHODS: This was a retrospective population-based cohort study of all endometrial cancers from the Vancouver Coastal Health authority region from 2011 to 2016, for which adjuvant therapy (radiotherapy and/or chemotherapy) was administered. Primary outcome measure was recurrence rates, expressed per 100â¯person-years (p100â¯py). Progression free survival (PFS) and overall survival (OS) rates were compared using Kaplan-Meier method and log-rank tests, and covariates were evaluated using Cox proportional hazards regression. RESULTS: There were 535 patients who received adjuvant therapy (radiotherapy and/or chemotherapy), including 162 (30.3%) and 373 (69.7%) with MMR-deficient and proficient tumors, respectively. Demographic variables were similar except MMR-deficient patients were younger (62.0 vs. 64.8, pâ¯=â¯0.01). Patients with MMR-deficient tumors were more likely to have endometrioid histotype (85.8% vs. 61.4%), more likely to have Stage I disease (62.3% vs 54.7%), and LVSI (65.4% vs. 53.4%) compared to those with MMR-proficient tumors. There was a trend for MMR-proficient group to have higher recurrence rates (10.7â¯p100â¯py vs 5.9â¯p100â¯py) and MMR deficiency was associated with better OS and PFS, but on multivariable analysis, MMR status was no longer significant. CONCLUSION: Women with MMR-deficient endometrial cancers who receive adjuvant therapy have a lower rate of recurrence compared to those with MMR-proficient cancers. However, on multivariable analysis, MMR status does not remain associated with differences in PFS or OS.
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Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/terapia , Recurrencia Local de Neoplasia/epidemiología , Anciano , Quimioradioterapia Adyuvante/métodos , Quimioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Endometrio/patología , Endometrio/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: There is uncertainty about the prognostic significance of mismatch repair (MMR) deficiency in endometrial cancer. The objective was to evaluate clinical characteristics and outcomes of endometrial cancers based on MMR status within a population-based study. METHODS: This was a retrospective population-based cohort study of all endometrial cancer cases from the Vancouver Coastal Health Authority region, evaluated for 4 MMR proteins using immunohistochemistry from 2012 to 2015. Patients were classified as MMR deficient (dMMR, any MMR protein absent) or MMR proficient (pMMR), Demographics, tumor characteristics, recurrences, and survival rates were compared according to MMR status. RESULTS: There were 892 patients, with 650 pMMR (72.5%) and 242 dMMR tumors. The dMMR group had more endometrioid tumors (87.6% vs 74.0%, P < 0.001), lymphovascular space invasion (43.8% vs 30.8%, P = 0.001), and dedifferentiation (5.9% vs 1.5%, P < 0.001), but fewer grade 1 tumors compared with the pMMR group (31.8% vs 40.8%, P < 0.001). Median progression-free survival and overall survival have not been reached. After a median follow-up of 31 months (1-99 months), there was no difference in progression or recurrence rates between pMMR and dMMR tumors (19.5% vs 16.5%; P = 0.31). However, among those with nonendometrioid tumors, recurrence and mortality rates were significantly higher for pMMR than dMMR tumors (42.0% vs 10.0%, P = 0.001, and 36.1% vs 13.1%, P = 0.01, respectively), despite similar stage and lymphovascular space invasion distributions. DISCUSSION: In this population-based study, there were no significant differences in recurrence or survival outcomes according to MMR status in endometrial cancer. However, among those with nonendometrioid tumors, there were lower recurrence and mortality rates associated with MMR-deficient compared with MMR-proficient tumors.
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Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Enzimas Reparadoras del ADN/biosíntesis , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/terapia , Estudios de Cohortes , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Femenino , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/biosíntesis , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Homólogo 1 de la Proteína MutL/biosíntesis , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/biosíntesis , Proteína 2 Homóloga a MutS/genética , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
As per the American Society for Colposcopy and Cervical Pathology guidelines, human papillomavirus (HPV) testing is currently used as part of cervical cancer screening and during colposcopy follow-up. The present project evaluated if the application of acetic acid (AA) impacts HPV test results. METHODS: We conducted a prospective nonrandomized interventional study. Participants referred for colposcopy were eligible if immunocompetent, older than 18 years, and not pregnant. Women in group A (controls) received 2 consecutive HPV tests without application of AA. Women in group B had a first HPV sample collected before the application of AA and a second sample collected 3 minutes after application of AA. Samples were tested for HPV DNA with Hybrid Capture 2 (HC2) according to the manufacturer's instructions. RESULTS: From October 17, 2012, to January 10, 2013, approximately 101 women were recruited in 2 colposcopy clinics. In each group, concordance was 98%, with only 1 participant having discordant results (testing negative on the first sample and positive on the second sample). We found no statistically significant difference in relative light units(RLUs) between groups (median of difference, - 0.02 vs -0.05 RLU; p = .93). CONCLUSIONS: The results of this study suggest that acetic acid at concentrations of 3% to 5% and sequential cervical sampling do not modify the result of HPV testing by Hybrid Capture 2.
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Ácido Acético , Colposcopía/métodos , Detección Precoz del Cáncer/métodos , Indicadores y Reactivos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Manejo de Especímenes/métodos , Adulto , Femenino , Humanos , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Trichoblastomas are rare and benign tumors that arise from rudimentary hair follicles. Presentation varies from superficial plaques to papular or nodular lesions. Trichoblastomas usually arise on the head or neck. A few cases of other vulvar trichoblastic tumors such as trichofibromas and trichoepitheliomas have been reported to this day, but no such report of vulvar trichoblastoma exists. MATERIALS AND METHODS: We report the case of a 61-year-old woman who presented with a vulvar trichoblastoma. The woman presented with a lump of the labium majus. She was managed surgically, first by wide excision of the mass followed by a second surgery consisting of a partial vulvectomy. Because surgical margins were positive and there is a potential for malignant transformation, a third surgery was performed. The margins came back negative. A literature review on trichoblastomas was performed, including its potential for malignant transformation, management, and immunohistochemistry to differentiate it from basal cell carcinoma. RESULTS: Trichoblastomas are benign tumors that have a potential for malignant transformation. These tumors can present aggressive characteristics. Differential diagnosis from basal cell carcinoma can be difficult but is facilitated using immunohistochemistry. CONCLUSIONS: This is the first case of vulvar trichoblastoma reported in the literature. Although it is a benign tumor, excision with negative margins is recommended because it can be difficult to distinguish from basal cell carcinoma and it has a potential for malignant transformation.