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1.
J Obstet Gynaecol ; : 1-5, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32312139

RESUMO

We compared wound dressing removal at 24 hours versus 48 hours following low-risk caesarean deliveries. This multicentre, randomised, controlled study included patients 18-44 years of age with low-risk term, singleton pregnancies. The randomisation was done weekly. Scheduled caesarean deliveries without labour were included. For comparison, the Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, Stay in hospital > 14 days (ASEPSIS) score for wound healing assessment was modified. The absolute scores were obtained based on a one-day reading rather than the five-day reading used in ASEPSIS. Zero ("0") was assigned as a complete healing. Higher scores were associated with more severe disruption of healing. The patients were enrolled between March 2015 and February 2017. The demographics were not statistically different. The wound scoring was similar in the groups at discharge and first-week evaluation. At the six weeks post-surgery, the wound scoring was significantly less in the 48-hour (3.9%) versus the 24-hour group (9%; p = .002). Dressing removal at 48 hours had a lower scoring in the low-risk population with scheduled caesarean deliveries.IMPACT STATEMENTWhat is already known on this subject? Surgical dressings are used to provide suitable conditions to heal caesarean incisions. There has been a limited number of studies on the evaluation of ideal timing on wound dressing removal after a caesarean delivery. These studies concluded there are no increased wound complications with removal at six hours versus 24 hours or within or beyond 48 hours after surgery.What do the results of this study add? The postoperative removal of the wound dressing at 48 hours had a lower wound score at six weeks than the removal at 24 hours for women with uncomplicated scheduled caesarean deliveries.What are the implications of these findings for clinical practice and/or further research? Early discharge after caesarean delivery is becoming more common. Dressing removal at 24 hours versus 48 hours becomes more crucial and needs to be clarified. Besides, high-risk populations, different skin closure techniques, and patients in labour should be addressed separately.

2.
Cancer ; 126(8): 1656-1667, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32037524

RESUMO

BACKGROUND: Human papillomavirus (HPV)-related disease remains a significant source of morbidity and mortality, and this underscores the need to increase HPV vaccination to reduce the burden of the disease. The objective of this study was to examine the association between the number of HPV vaccine doses and the risk of histologically confirmed preinvasive cervical disease and high-grade cytology. METHODS: This retrospective matched cohort study used administrative data from Optum's Clinformatics DataMart Database to identify females aged 9 to 26 years who received 1 or more quadrivalent HPV vaccine doses between January 2006 and June 2015. Cases and controls were matched on region, age, sexually transmitted disease history, and pregnancy. All had a Papanicolaou test ≥1 year after the date of the matched case's final dose. Cox proportional hazards models were used to examine the association between the number of HPV vaccine doses and the incidence of preinvasive cervical disease and high-grade cytology. The Kaplan-Meier method was used to estimate the cumulative incidence rate at the 5-year follow-up. RESULTS: The study included 133,082 females (66,541 vaccinated and 66,541 unvaccinated) stratified by the number of HPV vaccine doses and the vaccine initiation age. Among those aged 15 to 19 years, the hazard ratio (HR) for high-grade cytology for the 3-dose group was 0.84 (95% confidence interval [CI], 0.73-0.97), whereas the HRs for histologically confirmed preinvasive cervical disease for 1, 2, and 3 doses were 0.64 (95% CI, 0.47-0.88), 0.72 (95% CI, 0.54-0.95), and 0.66 (95% CI, 0.55-0.80), respectively. CONCLUSIONS: The receipt of 1, 2, or 3 doses of an HPV vaccine by females aged 15 to 19 years was associated with a lower incidence of preinvasive cervical disease in comparison with unvaccinated females, and this supports the use of any HPV vaccination in reducing the burden of the disease.

3.
Mol Oncol ; 14(3): 645-656, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31891442

RESUMO

Endometrial cancer is the most common gynecologic malignancy in developed countries. The antibody-drug conjugate (ADC) sacituzumab govitecan (SG) targets trophoblast cell-surface antigen-2 (Trop-2) - a cell-surface glycoprotein highly expressed in many epithelial tumors - and delivers the active metabolite of irinotecan SN-38 to Trop-2-positive tumor cells. We evaluated Trop-2 expression in endometrial endometrioid carcinoma (EC) tissues and the activity of SG against primary poorly differentiated EC cell lines and xenografts. Trop-2 expression was assessed in 143 formalin-fixed-paraffin-embedded tumors and seven primary tumor cell lines by immunohistochemistry and flow cytometry, respectively. Cell viability of primary tumor cell lines was assessed following exposure to SG, or control antibodies. Antibody-dependent cell cytotoxicity (ADCC) against Trop-2-positive and Trop-2-negative EC cell lines was measured in vitro using 4-h chromium release assays. A Trop-2-positive EC xenograft model was used to determine the in vivo activity of SG. Moderate-to-strong staining was detected in 84% (120/143) of EC samples, whereas 43% (3/7) of the primary EC cell lines tested overexpressed Trop-2. EC cell lines overexpressing Trop-2 were significantly more sensitive to SG compared to control ADC (P = 0.014 and P = 0.005). Both SG and the unconjugated parental antibody hRS7 mediated high ADCC against Trop-2-positive cell lines. Moreover, SG induced significant bystander killing of Trop-2-negative tumors cocultured with Trop-2-positive tumors. In the xenograft model, intravenous administration of SG twice weekly for three weeks was well tolerated and demonstrated impressive tumor growth inhibition against poorly differentiated, chemotherapy-resistant EC xenografts (P = 0.011). In summary, SG is a novel ADC with remarkable preclinical activity against poorly differentiated EC cell lines overexpressing Trop-2. These findings warrant future clinical trials.

4.
Sci Rep ; 10(1): 973, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969666

RESUMO

Human trophoblast cell-surface marker (Trop-2) is a surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of human epithelial solid tumors. We investigated the efficacy of sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised of a humanized anti- Trop-2 antibody, conjugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer cell lines and a xenograft model. Trop-2 expression was evaluated in 147 primary cervical tumors by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. For in vitro experiments, two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) cell lines were used. A cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models. Out of 147 primary cervical cancers, 113 were squamous cell carcinomas (SCCs), and 34 were adenocarcinoma/adenosquamous carcinomas. Moderate to strong diffuse staining was seen in 95% (108/113) of SCCs, and 81% (29/34) of adenocarcinoma/adenosquamous cancers on immunohistochemistry. Trop-2 positive cell lines were highly sensitive to sacituzumab govitecan in vitro, with IC50 values in the range of 0.18 to 0.26 nM (p = 0.02, and p = 0.04 for CVX-8, and ADX-3, respectively). In xenografts, a significant tumor growth inhibition was seen after twice-weekly intravenous administration of the drug for three weeks (p < 0.0001, and p = 0.001 for sacituzumab govitecan vs naked antibody, and sacituzumab govitecan vs control-ADC, respectively). Overall survival at 90 days was significantly improved in the sacituzumab govitecan group (p = 0.014). In conclusion, sacituzumab govitecan may represent a novel targeted therapy option in cervical cancer patients overexpressing Trop-2.

5.
Gynecol Oncol ; 156(2): 430-438, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31839338

RESUMO

OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer with poor prognosis. Sacituzumab govitecan (SG) is a novel antibody-drug-conjugate (ADC) targeting trophoblast cell-surface antigen 2 (Trop-2), a transmembrane-calcium-signal-transducer, to deliver SN-38, the active metabolite of irinotecan. The objective of this study was to evaluate the expression of Trop-2 in USC and the preclinical activity of SG against primary USC cell-lines and xenografts. METHODS: We used immunohistochemistry (IHC) and flow-cytometry-based assays to evaluate Trop-2 expression and cell-viability in USC tissue and primary tumor-cell-lines after exposure to SG, non-targeting control ADC, and naked antibody hRS7-IgG. Antibody-dependent-cell-cytotoxicity (ADCC) against Trop-2+ and Trop-2- USC cell-lines was evaluated in vitro using 4-hr-Chromium-release-assays. In vivo activity of SG was tested against Trop-2+ USC xenografts by intravenous administration of SG, control ADC, and hRS7. RESULTS: Trop-2 expression by IHC was detected in 95.1% of USC samples (99/104). Primary tumor cell-lines overexpressing Trop-2 were significantly more sensitive to SG when compared to control ADC (p <0.05). Both SG and hRS7 mediated ADCC in Trop2+ USC cell-lines while no cytotoxicity was detected against Trop-2- cells. SG induced significant bystander killing of Trop-2- tumors when admixed with Trop-2+ tumors. SG caused growth-inhibition and increased survival in SG treated mice harboring Trop-2+ xenografts when compared to controls (p <0.05). CONCLUSIONS: SG is remarkably active against USC overexpressing Trop-2 in vitro and in vivo. Our results combined with SG clinical responses recently reported against multiple chemotherapy resistant human tumors further support clinical development of SG in USC patients with advanced/recurrent disease.

6.
Curr Opin Obstet Gynecol ; 32(1): 57-64, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31833974

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to describe the role of the human epidermal growth factor receptor 2 (HER2) as a biomarker and potential target in gynecologic malignancies and to describe contemporary updates in the use of anti-HER2 treatments for these cancers. RECENT FINDINGS: Approximately 25-30% of all patients with uterine serous carcinoma overexpress tumoral HER2. The anti-HER2 antibody trastuzumab represents an effective, targeted therapy with significant efficacy in the treatment of HER2-positive breast and gastric cancer. Recently, trastuzumab efficacy has also been demonstrated in a randomized controlled trial of women with advanced or recurrent uterine serous carcinoma. Additionally, trastuzumab may be effective in women with HER2-positive uterine carcinosarcoma. The role of anti-HER2 therapy is unclear in women with other gynecologic malignancies but is being evaluated. SUMMARY: HER2 amplification/overexpression is an effective therapeutic target in select gynecologic malignancies, and especially in the rare endometrial cancer subtype, uterine serous carcinoma. As anti-HER2-targeted therapies become increasingly available, more treatment options may become available for women with HER2-positive disease.

7.
Proc Natl Acad Sci U S A ; 116(45): 22730-22736, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31624127

RESUMO

The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs). Somatic copy number variants (CNVs) identified 12 copy number gains and 40 losses, occurring more often than expected by chance, with the most frequent events in pathways similar to those found from analysis of single nucleotide variants (SNVs), including the ERBB2/PI3K/AKT/mTOR, apoptosis, chromatin remodeling, and cell cycle. To validate specific SNVs as targets, we took advantage of primary cervical tumor cell lines and xenografts to preclinically evaluate the activity of pan-HER (afatinib and neratinib) and PIK3CA (copanlisib) inhibitors, alone and in combination, against tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway (71%). Tumors harboring ERBB2 (5.8%) domain mutations were significantly more sensitive to single agents afatinib or neratinib when compared to wild-type tumors in preclinical in vitro and in vivo models (P = 0.001). In contrast, pan-HER and PIK3CA inhibitors demonstrated limited in vitro activity and were only transiently effective in controlling in vivo growth of PIK3CA-mutated cervical cancer xenografts. Importantly, combinations of copanlisib and neratinib were highly synergistic, inducing long-lasting regression of tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway. These findings define the genetic landscape of cervical cancer, suggesting that a large subset of cervical tumors might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs.

8.
Gynecol Oncol ; 155(1): 144-150, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31434613

RESUMO

OBJECTIVES: Cervical cancer (CC) remains a major health problem worldwide. Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutics in ovarian cancer. We explored the preclinical in vitro and in vivo activity of olaparib against multiple primary whole exome sequenced (WES) CC cells lines and xenografts. METHODS: Olaparib cell-cycle, apoptosis, homologous-recombination-deficiency (HRD), PARP trapping and cytotoxicity activity was evaluated against 9 primary CC cell lines in vitro. PARP and PAR expression were analyzed by Western blot assays. Finally, olaparib in vivo antitumor activity was tested against CC xenografts. RESULTS: While none of the cell lines demonstrated HRD, three out of 9 (33.3%) primary CC cell lines showed strong PARylation activity and demonstrated high sensitivity to olaparib in vitro treatment (cutoff IC50 values < 2 µM, p = 0.0012). Olaparib suppressed CC cell growth through cell cycle arrest in the G2/M phase and caused apoptosis (p < 0.0001). Olaparib activity in CC involved both PARP enzyme inhibition and trapping. In vivo, olaparib significantly impaired CC xenografts tumor growth (p = 0.0017) and increased overall animal survival (p = 0.008). CONCLUSIONS: A subset of CC primary cell lines is highly responsive to olaparib treatment in vitro and in vivo. High level of PARylation correlated with olaparib preclinical activity and may represent a useful biomarker for the identification of CC patients benefitting the most from PARPi.


Assuntos
Ftalazinas/farmacologia , Piperazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/enzimologia , Adulto , Animais , Apoptose/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Camundongos SCID , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
9.
Gynecol Oncol ; 155(2): 384-385, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31345607

RESUMO

OBJECTIVE: To demonstrate a surgical video, wherein a robotic-assisted posterior exenteration was performed for management of recurrent vaginal cancer. METHODS: We present a case of a 55 year-old female with a history of stage II squamous cell vaginal carcinoma. Patient recurred two years after completion of her primary chemoradiation at the posterior upper vagina. Pelvic MRI showed an approximately 4 cm tumoral nodule, without invasion into rectum or to bilateral parametria. PET-CT ruled out any metastatic disease. She was explained of the palliative systemic treatment versus potentially curative pelvic exenteration, as her options. After extensive counseling, she opted for the surgical option. Given her extensive comorbidities, including poorly controlled diabetes, COPD, obesity and heavy smoking, decision was made to attempt the procedure with a robotic approach (Behbehani et al.; Kammar et al. [1,2]). The technical steps of posterior Type IIB exenteration have been detailed in the video with an emphasis on anatomic landmarks by utilizing visual illustrations (Cibula [3]). The surgical margins were deemed to be negative with frozen section evaluation. Intravenous indocyanine green injection confirmed adequate blood supply to the end colostomy site. Patency of bilateral ureters was confirmed at the end of the procedure. RESULTS: Robotic-assisted Type IIB posterior pelvic exenteration was successfully completed without any intra-operative complications. Patient was discharged home on post-operative day 8. She has been dispositioned to surveillance. CONCLUSIONS: Robotic approach to highly morbid pelvic exenteration procedures should be considered in selected patients with recurrent gynecologic malignancies, who present without evidence of distant metastatic disease.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Vaginais/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Exenteração Pélvica/métodos
10.
Gynecol Oncol ; 153(1): 158-164, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30630630

RESUMO

OBJECTIVE: Aberrant expression of HER2/neu and PIK3CA gene products secondary to amplification/mutations are common in high-grade-serous-endometrial (USC) and ovarian-cancers (HGSOC). Because scant information is currently available in the literature on the potential negative effect of PIK3CA mutations on the activity of afatinib, in this study we evaluate for the first time the role of oncogenic PIK3CA mutations as a potential mechanism of resistance to afatinib in HGSOC and USC overexpressing HER2/neu. METHODS: We used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC. Primary-USC harboring wild-type-PIK3CA gene was transfected with plasmids encoding oncogenic PIK3CA-mutations (H1047R/E545K). The effect of afatinib on HER2/PI3K/AKT/mTOR pathway was evaluated by immunoblotting. RESULTS: We found PI3K wild-type cell-lines to be significantly more sensitive (lower IC50) than PI3K-mutated cell-lines p = 0.004). In vivo, xenografts of primary cell-line USC-ARK2, transfected with the PIK3CA-H1047R or E545K hotspot-mutations, exhibited significantly more rapid tumor growth when treated with afatinib, compared to mice harboring ARK2-tumors transfected with wild-type-PIK3CA (p = 0.041 and 0.001, respectively). By western-blot, afatinib effectively reduced total and phospho-HER2 proteins in all cell-lines. However, H1047R/E545K-PIK3CA-transfected-ARK2-cells demonstrated a greater compensatory increase in phosphorylated-AKT proteins after afatinib exposure when compared to controls ARK2. CONCLUSIONS: Oncogenic PI3K mutations may represent a major mechanism of resistance to afatinib. Combinations of c-erb with PIK3CA, AKT or mTOR inhibitors may be necessary to more efficiently block the PIK3CA/AKT/mTOR pathway.


Assuntos
Afatinib/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias dos Genitais Femininos/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Adulto , Idoso , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/biossíntese , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Neoplasias dos Genitais Femininos/enzimologia , Neoplasias dos Genitais Femininos/genética , Humanos , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Mutação , Fosfatidilinositol 3-Quinases/biossíntese , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/biossíntese , Receptor ErbB-2/genética , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Proc Natl Acad Sci U S A ; 116(2): 619-624, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30584090

RESUMO

Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBOC) to evaluate the evolutionary history. Lastly, to search for therapeutic targets, we evaluated the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 on primary tumors and xenografts harboring c-MYC amplifications. In line with previous studies, the large majority of germline and somatic mutations were found in BRCA1/2 (21%) and TP53 (86%) genes, respectively. Among mutations in known cancer driver genes, 77% were transmitted from primary tumors to metastatic tumors, and 80% from primary to recurrent tumors, indicating that driver mutations are commonly retained during ovarian cancer evolution. Importantly, the number, mutation spectra, and signatures in matched primary-metastatic tumors were extremely similar, suggesting transcoelomic metastases as an early dissemination process using preexisting metastatic ability rather than an evolution model. Similarly, comparison of SBOC showed extensive sharing of somatic mutations, unequivocally indicating a common ancestry in all cases. Among the 17 patients with matched tumors, four patients gained PIK3CA amplifications and two patients gained c-MYC amplifications in the recurrent tumors, with no loss of amplification or gain of deletions. Primary cell lines and xenografts derived from chemotherapy-resistant tumors demonstrated sensitivity to JQ1 and GS-626510 (P = 0.01), suggesting that oral BET inhibitors represent a class of personalized therapeutics in patients harboring recurrent/chemotherapy-resistant disease.


Assuntos
Antineoplásicos/farmacologia , Azepinas/farmacologia , Mutação , Recidiva Local de Neoplasia , Proteínas , Proteínas Proto-Oncogênicas c-myc , Triazóis/farmacologia , Animais , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Humanos , Camundongos , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Neoplasias Ovarianas , Proteínas/antagonistas & inibidores , Proteínas/genética , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
13.
Artigo em Inglês | MEDLINE | ID: mdl-30489341

RESUMO

OBJECTIVES: The aims of this study were to evaluate the association of preoperative pelvic pain with operative characteristics and the association of patient and operative characteristics with postoperative pain. METHODS: This is a retrospective cohort study utilizing Clinformatics DataMart, a large national commercial insurance database. We collected data for patients older than 18 years who underwent apical prolapse surgery between January 2005 and December 2014. We stratified data by preoperative (prior) pain and analyzed for associations of prior and postoperative pain. Logistic regression analysis was performed using SAS software. RESULTS: A total of 14,440 patients met inclusion criteria and were analyzed. Patients with prior pain were more likely to have an abdominal (open or laparoscopic) approach, a concomitant hysterectomy, but less likely to have additional repairs or a mesh insertion (P < 0.001). Postoperative pain was less with a concomitant hysterectomy, whether they had prior pain (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.41-0.77) or not (OR, 0.68; 95% CI, 0.56-0.82). Additional vaginal repairs were associated with more postoperative pain for those without prior pain (OR, 1.63; 95% CI, 1.3-2.04). Age older than 45 years was associated with less pain. Length of hospital stay of more than 2 days was associated with more pain. CONCLUSIONS: Patients with prior pain were more likely to undergo an abdominal approach and have a concomitant hysterectomy. Postoperative pain was less with a concomitant hysterectomy, but more with additional vaginal repairs. There is a need to include pain as an outcome in future studies, particularly clinical trials.

14.
J Low Genit Tract Dis ; 22(3): 189-194, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29762430

RESUMO

OBJECTIVE: The aim of the study was to investigate the effects of 3 or less quadrivalent human papillomavirus (HPV) vaccine doses on anogenital warts in both males and females in the United States. MATERIALS AND METHODS: We conducted a retrospective database study that included males and females aged 9 to 26 years who received varying numbers of vaccine doses between 2006 and 2015. The primary outcome was the incidence of anogenital warts starting 3 months after the last dose of the HPV vaccine. Proportional hazard regression models were used to examine the association between the number of HPV vaccine doses and the incidence of anogenital warts. The Kaplan-Meier method was used to estimate the proportion of subjects. RESULTS: A total of 440,532 females and 133,394 males were included in the study. We found a significant 2-way interaction (p < .0001) between the number of doses and age. For the group between 15 and 19 years of age, the hazard ratio of anogenital warts for the 3-dose vaccine was 0.58 (95% CI = 0.49-0.70), whereas it was 0.65 (95% CI = 0.49-0.85) and 0.67 (95% CI = 0.51-0.89) for the 1- and 2-dose groups, respectively. CONCLUSIONS: Our findings showed that 1, 2, and 3 doses of the quadrivalent HPV vaccine were similarly effective against anogenital warts in 15- to 19-year-old adolescents, irrespective of sex.


Assuntos
Doenças do Ânus/epidemiologia , Condiloma Acuminado/epidemiologia , Uso de Medicamentos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Adolescente , Adulto , Doenças do Ânus/prevenção & controle , Criança , Condiloma Acuminado/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
16.
Reprod Sci ; 25(6): 802-817, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29320955

RESUMO

INTRODUCTION: Statins are a class of drugs, which act by inhibiting the rate-limiting enzyme of cholesterol biosynthesis (3-hydroxy-3-methyl-glutaryl-CoA reductase). The inhibition of mevalonate synthesis leads to subsequent inhibition of downstream products of this pathway, which explains the pleiotropic effects of these agents in addition to their well-known lipid-lowering effects. Accumulating evidence suggests that statins might be beneficial in various obstetric and gynecologic conditions. METHODS: Literature searches were performed in PubMed and EMBASE for articles with content related to statins in obstetrics and gynecology. The findings are hereby reviewed and discussed. RESULTS: Inhibition of mevalonate pathway leads to subsequent inhibition of downstream products such as geranyl pyrophosphate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate. These products are required for proper intracellular localization of several proteins, which play important roles in signaling pathways by regulating membrane trafficking, motility, proliferation, differentiation, and cytoskeletal organization. The pleiotropic effects of statins can be summarized in 4 categories: antiproliferative, anti-invasive, anti-inflammatory, and antiangiogenic. The growing body of evidence is promising for these agents to be beneficial in endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome. Although in vivo studies showed varying degrees of benefit on fibroids and preterm birth, appropriately designed clinical trials are needed to make definitive conclusions. CONCLUSION: Statins might play a role in the treatment of endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome.


Assuntos
Doenças Urogenitais Femininas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Feminino , Doenças Urogenitais Femininas/metabolismo , Ginecologia , Humanos , Ácido Mevalônico/antagonistas & inibidores , Ácido Mevalônico/metabolismo , Obstetrícia , Transdução de Sinais , Resultado do Tratamento
18.
J Minim Invasive Gynecol ; 25(1): 30-37, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28970057

RESUMO

Bowel injury is a known inherent complication of minimally invasive gynecologic surgery; however, it does not automatically signify medical malpractice. Plaintiff attorneys representing patients seeking legal recourse from a bowel injury typically allege claims of intraoperative negligence, delay in diagnosis, or lack of informed consent in an effort to circumvent the assertion that it is a known inherent complication. In addition, damage awards in bowel injury lawsuits can easily exceed the amount covered by the policy limits of a medical malpractice insurance plan, leaving the gynecologist financially responsible for the difference. Therefore, it is crucial to understand when it may be appropriate to consent to a settlement offer, which can relieve the gynecologist from financial liability for amounts awarded above the medical malpractice policy limits. The purpose of this medical-legal review is to make minimally invasive gynecologic surgeons more aware of the legal strategies used by plaintiff attorneys representing patients who have incurred bowel injuries, and how to limit liability in lawsuits.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/legislação & jurisprudência , Enteropatias/etiologia , Jurisprudência , Imperícia/legislação & jurisprudência , Feminino , Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Ginecologia/legislação & jurisprudência , Ginecologia/estatística & dados numéricos , Humanos , Doença Iatrogênica/epidemiologia , Consentimento Livre e Esclarecido , Enteropatias/epidemiologia , Imperícia/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/legislação & jurisprudência , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos
19.
Front Surg ; 4: 15, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28352629

RESUMO

Power morcellation of surgical specimen during laparoscopic surgery is a practical technology that provides the opportunity to perform several minimally invasive procedures. However, this technology brought forward additional risks and complications associated with dissemination of both benign and malignant tissues inside the abdominal cavity. Based on startling cases, Food and Drug Administration (FDA) announced a discouraging statement on the use of power morcellators that decreased the number of minimally invasive approaches in the following period. As a response to these concerns and negative impacts of the FDA statement, researchers developed several new approaches resulting in contained or in-bag morcellation methods. In this review, we aimed to discuss these current methods and provide an insight for future developments.

20.
JSLS ; 20(4)2016.
Artigo em Inglês | MEDLINE | ID: mdl-27904309

RESUMO

BACKGROUND AND OBJECTIVES: Cervical insufficiency is a difficult condition to diagnose and can lead to preterm birth, miscarriage, or perinatal infant morbidity and mortality. We conducted this retrospective case study and literature review to evaluate the safety and efficacy of robot-assisted abdominal cerclage during pregnancy. METHODS: We conducted a case series and a systematic review that included patients who underwent robot-assisted abdominal cerclage during pregnancy from January 2010 through March 2016. RESULTS: Six patients met the criteria for the case series. Median age was 34 years (range, 28-37) at the time of the procedure. In 5 cases, the indication for transabdominal cerclage was a failed vaginal cerclage in a previous pregnancy, whereas a scarred and shortened cervix caused by a previous dilatation and curettage-induced cervical laceration was the indication in the remaining case. Median operating time was 159.5 minutes (range, 124-204), and median estimated blood loss was 25 mL (range, 10-25). No surgeries were converted to laparotomies; all patients were discharged on postoperative day 1. The median gestational age at delivery was 37.5 weeks (range, 22-39). Five patients delivered between 36 and 39 weeks. No patients had chorioamnionitis or preterm premature rupture of membranes. One patient went into preterm labor at 22 weeks, and the cerclage was removed via minilaparotomy. Eight articles met the criteria for systematic review. Sixteen patients underwent robot-assisted abdominal cerclage during pregnancy. Median age was 31.5 years (range, 25-37). The major indication in most articles was previous failed transvaginal cerclage. The median gestational ages at time of procedure and delivery were 12 weeks (range, 10-15) and 37 weeks (range, 33-39), respectively. CONCLUSION: Robot-assisted abdominal cerclage is safe and effective during pregnancy.


Assuntos
Cerclagem Cervical/métodos , Complicações na Gravidez , Robótica/métodos , Incompetência do Colo do Útero/cirurgia , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Estudos Retrospectivos
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