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OBJECTIVE: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC). METHODS: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling. RESULTS: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups. CONCLUSION: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.
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Neoplasias Endometriales , Hospitales Comunitarios , Histerectomía , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela , Humanos , Femenino , Persona de Mediana Edad , Hospitales Comunitarios/estadística & datos numéricos , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/diagnóstico , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático Centinela/métodos , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Estudios Retrospectivos , Anciano , Adulto , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Carcinoma in Situ/diagnósticoRESUMEN
CONTEXT: Enhanced Recovery After Surgery (ERAS) protocols have been shown to decrease length of stay and postoperative opioid usage in colorectal and bariatric surgeries performed at large academic centers. Hysterectomies are the second most common surgical procedure among women in the United States. Hysterectomies performed in an open fashion, or total abdominal hysterectomies (TAHs), account for a large portion of procedures performed by gynecologic oncologists secondary to current oncology guidelines and surgical complexity. Implementation of an ERAS protocol for gynecologic oncology TAHs is one way in which patient outcomes may be improved. OBJECTIVES: An ERAS protocol for gynecologic oncology surgeries performed in a community hospital was instituted with the goal to optimize patient outcomes preoperatively. The primary outcome of interest was to reduce patient opioid usage. Secondary outcomes included compliance with the ERAS protocol, length of stay, and cost. Thirdly, this study aimed to demonstrate the unique challenges of implementing a large-scale protocol across a community network. METHODS: An ERAS protocol was implemented in 2018, with multidisciplinary input from the Departments of Gynecologic Oncology, Anesthesia, Pharmacy, Nursing, Information Technology, and Quality Improvement to develop a comprehensive ERAS order set. This was implemented across a 12-site hospital system network that consisted of both urban and rural hospital settings. A retrospective review of patient charts was performed to assess measured outcomes. Parametric and nonparametric tests were utilized for statistical analysis with p<0.05 denoting statistical significance. If the p value was >0.05 and <0.09, this was considered a trend toward significant. RESULTS: A total of 124 patients underwent a TAH utilizing the ERAS protocol during 2018 and 2019. The control arm consisted of 59 patients who underwent a TAH prior to the ERAS protocol intervention, which was the standard of care in 2017. After 2 years of implementation of the ERAS protocol intervention, we found that 48â¯% of the ERAS patients had minimal opioid requirements after surgery (oral morphine equivalent [OME] range 0-40) with decreased postoperative opioid requirements in the ERAS group (p=0.03). Although not statistically significant, utilization of the ERAS protocol for gynecologic oncology TAHs trended toward shorter hospital length of stay from 5.18 to 4.17 days (p=0.07). The median total hospital costs per patient also showed a nonsignificant decrease in cost from $13,342.00 in the non-ERAS cohort and $13,703.00 in the ERAS cohort (p=0.8). CONCLUSIONS: A large-scale quality improvement (QI) initiative is feasible utilizing a multidisciplinary team to implement an ERAS protocol for TAHs in the division of Gynecologic Oncology with promising results. This large-scale QI result was comparable to studies that conducted quality-improvement ERAS initiatives at single academic institutions and should be considered within community networks.
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Recuperación Mejorada Después de la Cirugía , Neoplasias de los Genitales Femeninos , Femenino , Humanos , Estados Unidos , Neoplasias de los Genitales Femeninos/cirugía , Analgésicos Opioides , Mejoramiento de la Calidad , HisterectomíaRESUMEN
The fields of Obstetrics and Gynecology and Critical Care often share medically and surgically complex patients. Peripartum anatomic and physiologic changes can predispose or exacerbate certain conditions and rapid action is often needed. This review discusses some of the most common conditions responsible for the admission of obstetrical and gynecological patients to the critical care unit. We will consider both obstetrical and gynecologic concepts including postpartum hemorrhage, antepartum hemorrhage, abnormal uterine bleeding, preeclampsia and eclampsia, venous thromboembolism, amniotic fluid embolism, sepsis and septic shock, obstetrical trauma, acute abdomen, malignancies, peripartum cardiomyopathy, and substance abuse. This article aims to be a primer for the Critical Care provider.
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OBJECTIVE: The objective of this study is to evaluate factors associated with obstetric anal sphincter injury and identify modifiable risks. METHODS: A retrospective case-control study was performed in women who gave birth at our institution between May 2008 and December 2012. Patients who had a third- or fourth-degree lacerations were compared with those who did not. Parity, stretch marks, age, body mass index, tobacco use, fetal weight, operative delivery, labor, and second stage duration were compared between groups. Multivariate direct logistic regression was conducted on all patients who had complete data to calculate the adjusted odds ratio. RESULTS: We identified 299 patients with third- or fourth-degree lacerations and 8,459 patients without third- or fourth-degree lacerations during the time frame. Duration of second stage between 1 hour and 2 hours (P < 0.0001), duration of second stage greater than 2 hours (P < 0.0001), midline or unknown type episiotomy (P < 0.0001), mediolateral episiotomy (P < 0.0001), vacuum delivery (P < 0.0001), forceps delivery (P < 0.0001), fetal weight greater than 4,000 g (P < 0.0001), and antepartum stress urinary incontinence (P < 0.006) were associated with a significant increase in high-risk lacerations. This study did not find a statistically significant association between parity and these lacerations. CONCLUSIONS: We, as others, found that episiotomy and operative delivery were modifiable risks of obstetrical care. Furthermore, even a short second stage of labor (1-2 hours) was associated with significant risk of injury.
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Laceraciones , Complicaciones del Trabajo de Parto , Canal Anal/lesiones , Estudios de Casos y Controles , Parto Obstétrico/efectos adversos , Episiotomía/efectos adversos , Femenino , Humanos , Laceraciones/epidemiología , Laceraciones/etiología , Complicaciones del Trabajo de Parto/epidemiología , Complicaciones del Trabajo de Parto/etiología , Perineo/lesiones , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
â¢Renocolic fistula is a rare complication from extended field radiation.â¢Pathogenesis may involve colonic mucosal ischemia from radiation-induced colitis.â¢Conservative management with urethral stenting can result in complete resolution.
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El término enfermedad trofoblástica gestacional agrupa a un conjunto de trastornos caracterizados por una proliferación anormal de las vellosidades coriales placentarias. Las variedades más conocidas son la mola hidatiforme (completa y parcial), la mola invasora y el coriocarcinoma. Se presentan datos epidemiológicos, incluidos los factores de riesgo, una revisión sumaria de los rasgos clínicos y se enfatizan los cambios anatomopatológicos. A continuación se tratan aspectos diversos de entidades más raras como el tumor trofoblástico del sitio de implantación placentaria, y el tumor trofoblástico epiteliode. Para la estadificación se recurre a los estadios propuestos por la FIGO, aunque el uso de la tomografía con emisión de positrones, la biopsia de ganglio centinela y la quimioterapia neoadyuvante no están previstas en el esquema de la FIGO. El artículo está ilustrado con figuras a color y la bibliografía ha sido seleccionada y actualizada AU)
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Humanos , Femenino , Mola Hidatiforme , Vellosidades Coriónicas , Enfermedad Trofoblástica Gestacional , Muestra de la Vellosidad Coriónica , Factores Epidemiológicos , QuimioterapiaRESUMEN
â¢NACT use among SGO members for ovarian cancer is explored given recent trials.â¢Fewer SGO members feel they can't predict optimal cytoreduction pre-operatively.â¢Laparoscopy use has increased both for diagnosis and treatment of ovarian cancer.â¢Very high optimal cytoreduction rates are reported from SGO members.â¢Despite recent studies, SGO members don't regularly treat patients with NACT/ID.
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OBJECTIVE: We sought to validate the clinicopathologic implications and prognostic significance of ATR (ataxia telangiectasia mutated and Rad3-related) mutation in patients with endometrioid endometrial cancer and defective DNA mismatch repair enrolled in a cooperative group molecular staging study of endometrial cancer. METHODS: After pathology review, only endometrioid tumors with high neoplastic cellularity (≥70%) and high quality DNA for molecular analyses were included. MSI (microsatellite instability) typing was performed and the target sequence in exon 10 of ATR was evaluated by direct sequencing in all MSI-high tumors. Associations between ATR mutations and clinicopathologic variables were assessed using contingency table tests. Differences in overall survival (OS) and disease-free survival (DFS) were evaluated by univariate analyses and multivariable Cox proportional hazard models. RESULTS: A total of 475 eligible cases were identified. Of 368 MSI+ cases, the sequence of interest could be successfully genotyped in 357 cases. ATR mutations were exclusively identified in 46 tumors with high level microsatellite instability (MSI+) (12.9%, p<0.001) and were associated with higher tumor grade (p=0.001). ATR mutations were not associated with OS (HR 1.16; 95% CI, 0.58-2.32; p=0.68) or DFS (HR 0.61; 95% CI, 0.25-1.50; p=0.28). CONCLUSION: Truncating mutations in exon 10 of ATR occur exclusively in tumors with evidence of defective DNA mismatch repair. We were not able to confirm the prognostic value of these mutations in patients with endometrioid endometrial cancer.
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Biomarcadores de Tumor/genética , Carcinoma Endometrioide/genética , Neoplasias Endometriales/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de la Ataxia Telangiectasia Mutada/genética , Carcinoma Endometrioide/patología , Estudios de Cohortes , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/patología , Femenino , Humanos , Inestabilidad de Microsatélites , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVES: To evaluate knowledge of obesity-related peri-operative risks in with women newly diagnosed complex atypical hyperplasia and endometrial cancer. METHODS: Cross sectional study of patients newly diagnosed with complex atypical hyperplasia or endometrial cancer who underwent preoperative counseling between 2011 and 2014, using a 17-item questionnaire. Obesity was defined as body mass index (BMI) of 30 kg/m2 or greater. Bivariate analysis was conducted using Pearson's Chi-Square or Fisher's Exact tests where appropriate and Mann-Whitney U for continuous variables. RESULTS: Of 98 patients recruited, mean age was 58 years, 87% were obese, 83% white, and 51% had grade 1 endometrioid adenocarcinomas. Sixty-four percent of obese women reported that their physicians had discussed surgical risks related to obesity. However, 17% of obese and 42% of non-obese patients responded that they were unsure of the peri-operative risks associated with obesity. There was substantial lack of understanding among obese patients regarding their increased risks of respiratory problems (29%), thromboembolism (29%), heart attack (35%), or longer operating time (35%) and hospital stay (47%). However, obese patients were more aware of wound infection risks associated with obesity compared to their non-obese counterparts (72% vs. 31%, p=0.004). CONCLUSIONS: Pre-operative counseling for obese women with newly diagnosed endometrial cancer should incorporate more focused education about obesity-related risks. They report being knowledgeable about the risks associated with their surgery, however, more than a quarter are unaware of the impact obesity has on respiratory problems, thromboembolism, wound infection, heart attack or longer operating time and hospital stay.
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OBJECTIVES: Obese women have a high incidence of wound separation after gynecologic surgery. We explored the effect of a prospective care pathway on the incidence of wound complications. METHODS: Women with a body mass index (BMI) ≥30 kg/m(2) undergoing a gynecologic procedure by a gynecologic oncologist via a vertical abdominal incision were eligible. The surgical protocol required: skin and subcutaneous tissues to be incised using a scalpel or cutting electrocautery, fascial closure using #1 polydioxanone suture, placement of a 7 mm Jackson-Pratt drain below Camper's fascia, closure of Camper's fascia with 3-0 plain catgut suture and skin closure with staples. Wound complication was defined as the presence of either a wound infection or any separation. Demographic and perioperative data were analyzed using contingency tables. Univariable and multivariable regression models were used to identify predictors of wound complications. Patients were compared using a multivariable model to a historical group of obese patients to assess the efficacy of the care pathway. RESULTS: 105 women were enrolled with a median BMI of 38.1. Overall, 39 (37%) had a wound complication. Women with a BMI of 30-39.9 kg/m(2) had a significantly lower risk of wound complication as compared to those with a BMI >40 kg/m(2) (23% vs 59%, p<0.001). After controlling for factors associated with wound complications the prospective care pathway was associated with a significantly decreased wound complication rate in women with BMI <40 kg/m(2) (OR 0.40, 95% C.I.: 0.18-0.89). CONCLUSION: This surgical protocol leads to a decreased rate of wound complications among women with a BMI of 30-39.9 kg/m(2).
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Procedimientos Quirúrgicos Ginecológicos , Obesidad/complicaciones , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/prevención & control , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Adulto , Anciano , Protocolos Clínicos , Vías Clínicas , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Estudios Prospectivos , Dehiscencia de la Herida Operatoria/epidemiología , Infección de la Herida Quirúrgica/epidemiologíaRESUMEN
Tumors with defective mismatch repair acquire large numbers of strand slippage mutations including frameshifts in coding sequence repeats. We identified a mutational hotspot, p.T204fs, in the insulator-binding protein (CTCF) in MSI-positive endometrial cancers. Although CTCF was described as a significantly mutated gene by the endometrial cancer TCGA, the A7 track variants leading to T204 frameshifts were not reported. Reanalysis of TCGA data using Pindel revealed frequent T204fs mutations, confirming CTCF is an MSI target gene and revealed the same frameshifts in tumors with intact mismatch repair. We show that T204fs transcripts are subject to nonsense-mediated decay and as such, T204fs mutations are unlikely to act as dominant negatives. The spectrum and pattern of mutations observed is consistent with CTCF acting as a haploinsufficient tumor suppressor.
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Neoplasias Endometriales/genética , Mutación del Sistema de Lectura , Inestabilidad de Microsatélites , Proteínas Represoras/genética , Secuencia de Bases , Factor de Unión a CCCTC , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/patología , Exoma , Femenino , Variación Genética , Haploinsuficiencia , Humanos , Repeticiones de Microsatélite , Tasa de Mutación , Degradación de ARNm Mediada por Codón sin Sentido , Análisis de Secuencia de ADN , Proteínas Supresoras de Tumor/genéticaRESUMEN
OBJECTIVE: To characterize gynecologic oncology patients' perceptions of the process of disclosure of a cancer diagnosis. METHODS: We surveyed 100 gynecologic oncology patients between December 2011 and September 2012. An 83-item tool based on three validated assessment tools evaluated patient-centered factors, physician behavior and communication skills, and environmental factors. Associations between patients' satisfaction and these variables were analyzed using Wilcoxon rank-sum, Kruskal-Wallis, and Spearman's rho tests. Poisson regression was used to assess factors associated with patient's satisfaction. RESULTS: Twenty-four percent of patients were notified of their diagnosis by phone, 60% in the physician's office, and 16% in the hospital. Disclosure was performed by an obstetrician-gynecologist (58%), gynecologic oncologist (26%), primary care physician (8%), or other (8%). Fifty-two percent of all patients were accompanied by a support person. Higher patient satisfaction scores were associated with face-to-face disclosure (mean score 91% compared with over the phone 72%, P=.02), a private setting (mean score 92% compared with impersonal setting 72%, P=.004), and duration of the encounter of greater than 10 minutes (mean score 94% compared with less than 10 minutes 79%, P<.001). Multivariate analysis confirmed that both physician communication skills (P<.001) and patient-centered factors (eg, perception of physician sensitivity and empathy, opportunities to ask questions and express emotion, and set the pace of conversation; P=.013) were associated with higher patient satisfaction. CONCLUSIONS: Effective physician communication skills and patient-centered factors resulted in higher patient satisfaction with the gynecologic cancer diagnosis disclosure experience. LEVEL OF EVIDENCE: II.
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Comunicación , Revelación/normas , Neoplasias de los Genitales Femeninos/diagnóstico , Relaciones Médico-Paciente , Anciano , Estudios Transversales , Femenino , Neoplasias de los Genitales Femeninos/psicología , Humanos , Persona de Mediana Edad , Satisfacción del Paciente , Encuestas y CuestionariosRESUMEN
OBJECTIVE: We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC). METHODS: Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500 mg/m(2) IV and bevacizumab 15 mg/kg IV were administered every 3 weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS). RESULTS: Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Median follow-up was 25.7 months (range, 3.0-47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38-71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25-59), 18 stable disease (53%; 35-70) and 2 progressive disease (6%; 1-20). Median PFS was 7.9 months (95% CI, 4.6-10.9), with a median OS of 25.7 months (95% CI, 15.4-29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6 months prior to enrollment. Grade 3-4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment. CONCLUSIONS: Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Neoplasias de las Trompas Uterinas/patología , Femenino , Glutamatos/administración & dosificación , Glutamatos/efectos adversos , Guanina/administración & dosificación , Guanina/efectos adversos , Guanina/análogos & derivados , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Pemetrexed , Neoplasias Peritoneales/patología , Tasa de SupervivenciaRESUMEN
OBJECTIVE: The objective of this study was to assess patients' preferences of the timing of referral for genetic counseling and testing in relation to the diagnosis, treatment, and recurrence of ovarian, tubal, or primary peritoneal cancers. METHODS: Ninety-two patients who underwent counseling and testing by 1 certified genetic counselor were identified. An introductory letter, consent form, and questionnaire were mailed to gather information regarding factors influencing the decision to undergo genetic counseling and testing and opinions regarding optimal timing. Medical records were reviewed for demographic and clinical data. RESULTS: Of 47 consenting women, 45 underwent testing. Eight (18%) were found to have a genetic mutation. Women lacked consensus about the optimal time for referral for and to undergo genetic testing, although women with stage I disease preferred testing after completion of chemotherapy. Most women were comfortable receiving the results by phone, but one third preferred an office visit. CONCLUSIONS: Patients' views regarding the best time to be referred for and undergo counseling and testing varied greatly. Because of the high mortality of this disease, clinicians should discuss referral early and personalize the timing to each patient. The subset of patients who prefer results disclosure during an office visit should be identified at the time of their initial counseling.
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Neoplasias de las Trompas Uterinas/diagnóstico , Asesoramiento Genético/psicología , Pruebas Genéticas , Neoplasias Ováricas/diagnóstico , Neoplasias Peritoneales/diagnóstico , Derivación y Consulta , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/psicología , Anciano , Proteína BRCA1/genética , Proteína BRCA2/genética , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/psicología , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/psicología , Neoplasias de las Trompas Uterinas/genética , Neoplasias de las Trompas Uterinas/psicología , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Mutación/genética , Estadificación de Neoplasias , Neoplasias Ováricas/genética , Neoplasias Ováricas/psicología , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/psicología , Pronóstico , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: The aim of this study was to report clinical outcomes of cervical cancer patients treated with weekly cisplatin chemo-radiation therapy (chemoRT) stratified by pre-treatment cisplatin in vitro chemosensitivity. METHODS: This was a retrospective analysis of patients with cervical cancer seen at our institution between May 2009 and August 2011. Patients underwent pre-treatment in vitro chemoresponse testing (Precision Therapeutics, Inc.) and were treated with concurrent weekly cisplatin chemoRT. The study consisted of 33 patients with FIGO tumor stages Ib2 to IIIb. Pre-treatment cisplatin chemoresponse of individual patient tumors was determined from chemoresponse dose response curves and scored as responsive (R), intermediate response (IR), or nonresponsive (NR). RESULTS: There were 28 patients with squamous cell carcinoma and 5 with adenocarcinoma. Cisplatin chemosensitivity was R and IR in 18 patient specimens and NR in 15. The 2-year recurrence-free survivals (RFS) were 87% for patients whose specimens tested R+IR to cisplatin compared to 58% for those whose specimens were NR (p=0.036). The 2-year RFS were 86% for the R+IR group compared to 46% for the NR group for patients with tumors of squamous cell histology (p=0.009). Stepwise proportional hazards modeling for RFS demonstrated that chemoresponsiveness to cisplatin (p=0.029) and FDG-PET lymph node status (p=0.011) were the only independent predictors of RFS for patients with tumors of squamous cell histology. CONCLUSION: Pre-treatment in vitro cisplatin chemoresponse testing of cervix cancer biopsies was technically feasible and prognostic of RFS in patients treated with weekly cisplatin chemoRT.
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Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimioradioterapia , Supervivencia sin Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
OBJECTIVE: We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix. METHODS: Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy. RESULTS: Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities. CONCLUSION: The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Imagen Multimodal , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos X , Topotecan/administración & dosificación , Topotecan/efectos adversos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Adulto JovenRESUMEN
MicroRNAs (miRNAs) are endogenous, non-coding RNA transcripts that regulate gene expression. Here, we report 175 putative novel miRNAs identified in uterine cancers profiled by Next Generation Sequencing. Our data indicate that one of these putative miRNAs (BCM-173) is conserved across multiple species and is expressed at levels similar to known human miRNAs. Functionally, this miRNA promotes the growth and migration of uterine cancer cell lines by targeting vinculin and altering the distribution of focal adhesions. These results expand our insight into the repertoire of human miRNAs and identify novel pathways by which dysregulated miRNA expression promotes uterine cancer growth.
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Adenocarcinoma/genética , Adenocarcinoma/patología , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , MicroARNs/genética , Apoptosis/genética , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , MicroARNs/metabolismo , Análisis de Secuencia de ADN , Análisis de Secuencia de ARNRESUMEN
OBJECTIVE: Lithium chloride (LiCl) has been shown to demonstrate anticancer properties at supratherapeutic doses. This study was designed to determine whether LiCl, as a single agent or in combination with cytotoxic agents, reduces ovarian cancer cell growth and metabolic activity at clinically achievable levels. METHODS: We studied the effects of LiCl on 2 high-grade serous ovarian cancer cell lines, SKOV3 and OVCA 433, and primary cultures developed from ascitic fluid collected from patients with metastatic high-grade serous ovarian cancer. We assessed proliferation and metabolism using cell cycle analysis, MTT assays, and cellular proliferation and clonogenic potential assays. RESULTS: Treatment with 1 mM LiCl had no effect on the cell cycle distribution or metabolic activity of the SKOV3 and OVCA 433 cell lines. Combination treatment with cisplatin or paclitaxel led to statistically significant decreases in metabolic activity in the OVCA 433 cell line and 50% of cultures investigated. The decreased metabolic activity was not, however, associated with decreased cell growth or clonogenic potential. CONCLUSIONS: Combination treatment with LiCl and cytotoxic agents at physiologically achievable drug concentrations reduces ovarian cancer cell metabolism but does not appear to affect cellular proliferation. The potential for combined lithium/cytoxic therapies appears to be limited based on our analysis of both established cell lines and short-term ovarian cancer cultures.
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Cistadenocarcinoma Seroso/enzimología , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Cloruro de Litio/farmacología , Neoplasias Ováricas/enzimología , Inhibidores de Proteínas Quinasas/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cistadenocarcinoma Seroso/tratamiento farmacológico , Femenino , Glucógeno Sintasa Quinasa 3 beta , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Cultivo Primario de Células , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To estimate the accuracy of vaginal cytology in postoperative surveillance for detecting recurrent endometrial cancer and to estimate the optimal management of squamous abnormalities detected in this setting. METHODS: This review included women who underwent hysterectomy for endometrial cancer between January 1, 2006, and December 31, 2010, and had at least one postoperative Pap test. Clinical and demographic data were collected and outcomes including abnormal vaginal cytology, results of colposcopic examination, and endometrial cancer recurrence were assessed. A Cox regression model to estimate the risk of abnormal cytology was created. Sensitivity, specificity, and negative and positive predictive values of detecting vaginal recurrences were calculated. RESULTS: Four hundred thirty-three women contributed 2,378 Pap tests. At least one abnormal cytology result was found during follow-up of 55 (13%) women, representing 3% of all Pap tests. No recurrent endometrial cancers were diagnosed on the basis of isolated abnormal cytology. No cases of recurrent cancer were diagnosed in women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) Pap test results. In multivariable analysis, abnormal cytology was highly associated with prior postoperative radiation therapy (P<.001). The sensitivity, specificity, and positive and negative predictive values of an abnormal Pap test result in detecting a local recurrence are 40%, 87.9%, 7.3%, and 98.4%, respectively. CONCLUSION: Colposcopy is not needed after a Pap test result read as atypical squamous cells of undetermined significance or LSIL. LEVEL OF EVIDENCE: III.