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International Journal of Environmental... Apr 2022Regenerative medicine combines elements of tissue engineering and molecular biology aiming to support the regeneration and repair processes of damaged tissues, cells and... (Review)
Review
Regenerative medicine combines elements of tissue engineering and molecular biology aiming to support the regeneration and repair processes of damaged tissues, cells and organs. The most commonly used preparation in regenerative medicine is platelet rich plasma (PRP) containing numerous growth factors present in platelet granularities. This therapy is increasingly used in various fields of medicine. This article is a review of literature on the use of PRP in gynecology and obstetrics. There is no doubt that the released growth factors and proteins have a beneficial effect on wound healing and regeneration processes. So far, its widest application is in reproductive medicine, especially in cases of thin endometrium, Asherman's syndrome, or premature ovarian failure (POF) but also in wound healing and lower urinary tract symptoms (LUTS), such as urinary incontinence or recurrent genitourinary fistula auxiliary treatment. Further research is, however, needed to confirm the effectiveness and the possibility of its application in many other disorders.
Topics: Endometrium; Female; Gynecology; Humans; Platelet-Rich Plasma; Pregnancy; Regenerative Medicine; Tissue Engineering
PubMed: 35564681
DOI: 10.3390/ijerph19095284 -
Cureus Oct 2022Chronic pelvic pain (CPP) is explained as a complaint of cyclic or non-cyclic pelvic pain lasting for at least six months with or without dysmenorrhea, dyspareunia,... (Review)
Review
Chronic pelvic pain (CPP) is explained as a complaint of cyclic or non-cyclic pelvic pain lasting for at least six months with or without dysmenorrhea, dyspareunia, dysuria, and dyschezia. The etiology of symptoms can be categorized according to organ system involvement. Gynecological causes typically involve endometriosis-related pain, pelvic congestion syndrome, pelvic inflammatory disease, adenomyosis, hydrosalpinx, etc. Endometriosis-related pain is seldom non-cyclic and may present due to recurrent bleeding in endometriotic implants. Engorgement of veins leads to inadequate venous washout and presents chronic pelvic pain in pelvic congestion syndrome. The pressure effect of benign lesions of the uterus and cervix may lead to cyclic pain, as in uterine fibroids. Often presentation of diseases like hydrosalpinx may not present until it has overdistended or may at times present as acute pelvic pain if it undergoes torsion. Long-standing untreated pelvic inflammatory diseases in sexually active females is another cause of pelvic pain. The complaint of CPP is also shared due to the involvement of the gastrointestinal system in conditions like irritable bowel syndrome, inflammatory bowel diseases, long-standing abdominal hernias, colorectal cancer, etc. Alteration of the gut biome and dysregulated brain-gut associations lead to typical manifestations of chronic lower back pain and pelvic pain in irritable bowel syndrome. Colorectal tumors, when in the advanced stage, may spread to nearby tissues creating fistulas and affecting nearby nerves, causing pelvic, perineal, and sacral pain. Abdominal hernias with small bowel prolapse are always related to pelvic pain symptoms. Infections in the urinary tract like urethral syndrome, chronic prostatitis, and chronic recurrent cystitis present with CPP and voiding problems. Musculoskeletal etiologies, though varying in degrees, are responsible for isolated complaints of CPP. Examples include pelvic girdle pain, levator syndrome, coccygodynia, and pelvic floor prolapse.
PubMed: 36465795
DOI: 10.7759/cureus.30691 -
International Journal of Gynecological... Mar 2022Vaginal cancer is a rare cancer. A lot of the data used in the treatment of this cancer are extrapolated from cervical cancer data. Radiation therapy plays a significant... (Review)
Review
Vaginal cancer is a rare cancer. A lot of the data used in the treatment of this cancer are extrapolated from cervical cancer data. Radiation therapy plays a significant role in the treatment of vaginal cancer. The advances in radiation therapy in both external beam and brachytherapy have improved local control, survival, and toxicity. Brachytherapy plays an important role in treating vaginal cancer, but treatment should be individualized to each tumor. Imaging, particularly magnetic resonance imaging, plays an essential role in the management of patients with vaginal cancer, from diagnosis to staging to treatment management to surveillance.
Topics: Brachytherapy; Carcinoma in Situ; Female; Humans; Magnetic Resonance Imaging; Uterine Cervical Neoplasms; Vagina; Vaginal Neoplasms
PubMed: 35256422
DOI: 10.1136/ijgc-2021-002517 -
The New England Journal of Medicine Feb 2014Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.
METHODS
Using a 2-by-2 factorial design, we randomly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight. Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area, plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3, plus paclitaxel at a dose of 175 mg per square meter on day 1. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented. The primary end point was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important.
RESULTS
Groups were well balanced with respect to age, histologic findings, performance status, previous use or nonuse of a radiosensitizing platinum agent, and disease status. Topotecan-paclitaxel was not superior to cisplatin-paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; 98% confidence interval, 0.54 to 0.95; P=0.004 in a one-sided test) and higher response rates (48% vs. 36%, P=0.008). Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%).
CONCLUSIONS
The addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival. (Funded by the National Cancer Institute; GOG 240 ClinicalTrials.gov number, NCT00803062.).
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cisplatin; Female; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Paclitaxel; Quality of Life; Survival Analysis; Topotecan; Uterine Cervical Neoplasms
PubMed: 24552320
DOI: 10.1056/NEJMoa1309748 -
American Journal of Obstetrics and... Jan 2020Without cesarean delivery, obstructed labor can result in maternal and fetal injuries or even death given a disproportion in size between the fetus and the maternal... (Review)
Review
Without cesarean delivery, obstructed labor can result in maternal and fetal injuries or even death given a disproportion in size between the fetus and the maternal birth canal. The precise frequency of obstructed labor is difficult to estimate because of the widespread use of cesarean delivery for indications other than proven cephalopelvic disproportion, but it has been estimated that at least 1 million mothers per year are affected by this disorder worldwide. Why is the fit between the fetus and the maternal pelvis so tight? Why did evolution not lead to a greater safety margin, as in other primates? Here we review current research and suggest new hypotheses on the evolution of human childbirth and pelvic morphology. In 1960, Washburn suggested that this obstetrical dilemma arose because the human pelvis is an evolutionary compromise between two functions, bipedal gait and childbirth. However, recent biomechanical and kinematic studies indicate that pelvic width does not considerably affect the efficiency of bipedal gait and thus is unlikely to have constrained the evolution of a wider birth canal. Instead, bipedalism may have primarily constrained the flexibility of the pubic symphysis during pregnancy, which opens much wider in most mammals with large fetuses than in humans. We argue that the birth canal is mainly constrained by the trade-off between 2 pregnancy-related functions: while a narrow pelvis is disadvantageous for childbirth, it offers better support for the weight exerted by the viscera and the large human fetus during the long gestation period. We discuss the implications of this hypothesis for understanding pelvic floor dysfunction. Furthermore, we propose that selection for a narrow pelvis has also acted in males because of the role of pelvic floor musculature in erectile function. Finally, we review the cliff-edge model of obstetric selection to explain why evolution cannot completely eliminate cephalopelvic disproportion. This model also predicts that the regular application of life-saving cesarean delivery has evolutionarily increased rates of cephalopelvic disproportion already. We address how evolutionary models contribute to understanding and decision making in obstetrics and gynecology as well as in devising health care policies.
Topics: Animals; Biological Evolution; Cephalopelvic Disproportion; Cesarean Section; Female; Gait; Hominidae; Humans; Parturition; Pelvic Bones; Pelvimetry; Pelvis; Pregnancy; Pubic Symphysis; Selection, Genetic
PubMed: 31251927
DOI: 10.1016/j.ajog.2019.06.043 -
Lancet (London, England) Oct 2017On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved... (Comparative Study)
Comparative Study Randomized Controlled Trial
Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240).
BACKGROUND
On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events.
METHODS
In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain. Inclusion criteria included a GOG performance status score of 0 or 1; adequate renal, hepatic, and bone marrow function; adequately anticoagulated thromboembolism; a urine protein to creatinine ratio of less than 1; and measurable disease. Patients who had received chemotherapy for recurrence and those with non-healing wounds or active bleeding conditions were ineligible. We randomly allocated patients 1:1:1:1 (blocking used; block size of four) to intravenous chemotherapy of either cisplatin (50 mg/m on day 1 or 2) plus paclitaxel (135 mg/m or 175 mg/m on day 1) or topotecan (0·75 mg/m on days 1-3) plus paclitaxel (175 mg/m on day 1) with or without intravenous bevacizumab (15 mg/kg on day 1) in 21 day cycles until disease progression, unacceptable toxic effects, voluntary withdrawal by the patient, or complete response. We stratified randomisation by GOG performance status (0 vs 1), previous radiosensitising platinum-based chemotherapy, and disease status (recurrent or persistent vs metastatic). We gave treatment open label. Primary outcomes were OS (analysed in the intention-to-treat population) and adverse events (analysed in all patients who received treatment and submitted adverse event information), assessed at the second interim and final analysis by the masked Data and Safety Monitoring Board. The cutoff for final analysis was 450 patients with 346 deaths. This trial is registered with ClinicalTrials.gov, number NCT00803062.
FINDINGS
Between April 6, 2009, and Jan 3, 2012, we enrolled 452 patients (225 [50%] in the two chemotherapy-alone groups and 227 [50%] in the two chemotherapy plus bevacizumab groups). By March 7, 2014, 348 deaths had occurred, meeting the prespecified cutoff for final analysis. The chemotherapy plus bevacizumab groups continued to show significant improvement in OS compared with the chemotherapy-alone groups: 16·8 months in the chemotherapy plus bevacizumab groups versus 13·3 months in the chemotherapy-alone groups (hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·007). Final OS among patients not receiving previous pelvic radiotherapy was 24·5 months versus 16·8 months (0·64 [0·37-1·10]; p=0·11). Postprogression OS was not significantly different between the chemotherapy plus bevacizumab groups (8·4 months) and chemotherapy-alone groups (7·1 months; 0·83 [0·66-1·05]; p=0·06). Fistula (any grade) occurred in 32 (15%) of 220 patients in the chemotherapy plus bevacizumab groups (all previously irradiated) versus three (1%) of 220 in the chemotherapy-alone groups (all previously irradiated). Grade 3 fistula developed in 13 (6%) versus one (<1%). No fistulas resulted in surgical emergencies, sepsis, or death.
INTERPRETATION
The benefit conferred by incorporation of bevacizumab is sustained with extended follow-up as evidenced by the overall survival curves remaining separated. After progression while receiving bevacizumab, we did not observe a negative rebound effect (ie, shorter survival after bevacizumab is stopped than after chemotherapy alone is stopped). These findings represent proof-of-concept of the efficacy and tolerability of antiangiogenesis therapy in advanced cervical cancer.
FUNDING
National Cancer Institute.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cisplatin; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Middle Aged; Paclitaxel; Topotecan; Uterine Cervical Neoplasms
PubMed: 28756902
DOI: 10.1016/S0140-6736(17)31607-0 -
Fertility and Sterility Oct 2021To quantify the efficacy of medical management of uterine arteriovenous malformation (AVM) and compare efficacy between different classes of medication. In addition, we... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To quantify the efficacy of medical management of uterine arteriovenous malformation (AVM) and compare efficacy between different classes of medication. In addition, we evaluated for factors associated with treatment success and pregnancy outcomes after medical management.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Thirty-two studies representing 121 premenopausal women with medically-treated uterine AVM were identified via database searches of MEDLINE, Embase, Web of Science, and cited references.
INTERVENTION(S)
Medical treatment with progestins, gonadotropin-releasing hormone agonists (GnRH-a), methotrexate, combined hormonal contraception , uterotonics, danazol, or combination of the above.
MAIN OUTCOME MEASURE(S)
Primary outcome of treatment success was defined as AVM resolution without subsequent procedural interventions. Secondary outcome was treatment complication (readmission or transfusion).
RESULT(S)
The overall success rate of medical management was 88% (106/121). After adjusting for clustering effects, success rates for progestin (82.5%; 95% confidence interval [CI], 70.1%-90.4%), GnRH-a (89.3%; 99% CI, 71.4%-96.5%) and methotrexate (90.0%; 99% CI, 55.8%-98.8%) were significantly different from the null hypothesis of 50% success. The agents with the lowest adjusted proportion of complications were progestins (10.0%; 99% CI, 3.3%-26.8%) and GnRH-a (10.7%; 99% CI, 3.5%-28.4%). No clinical factors were found to predict treatment success. Twenty-six subsequent pregnancies are described, with no reported recurrences of AVM.
CONCLUSION(S)
Medical management for uterine AVM is a reasonable approach in a well selected patient. These data should be interpreted in the context of significant publication bias.
Topics: Arteriovenous Fistula; Blood Transfusion; Clinical Decision-Making; Female; Humans; Patient Readmission; Patient Selection; Pregnancy; Pregnancy Rate; Risk Assessment; Risk Factors; Treatment Outcome; Uterine Artery; Uterus
PubMed: 34130801
DOI: 10.1016/j.fertnstert.2021.05.095