RESUMO
Background Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and imaging. Results 34 subjects were screened, 23 treated and 21 remained on study for ≥12 weeks. The median PSA was 6.4 ng/ml (range 1.7-80.1); doubling-time 6.2 months (range 1.4-36.6) and baseline testosterone 319.1 ng/ml (range 2.5-913.7). Median duration of therapy was 6.5 months (2.6-14.0). CTCs (median 48.5 cells/4 ml (range 15-268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by ≥50% in 4.3% (1 subject). No patients developed metastatic disease while on treatment (metastases free survival =100%). There were no treatment-related adverse events (AEs) and quality of life was unchanged from baseline on the EORTC QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were unrelated to efficacy or toxicity. Conclusions Use of SM-88 was associated with disease control while maintaining QOL. SM-88 may delay the need for ADT and the associated hormonal side effects. Larger trials are planned.Trial registration number, date of registration - NCT02796898, June 13, 2016.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Tirosina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Metoxaleno/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Fenitoína/administração & dosagem , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Qualidade de Vida , Sirolimo/administração & dosagem , Tirosina/administração & dosagem , Tirosina/efeitos adversos , Tirosina/uso terapêuticoRESUMO
Purpose SM-88 (D,L-alpha-metyrosine; racemetyrosine) is a novel anti-cancer agent, used with melanin, phenytoin, and sirolimus (SMK Therapy). This pilot first-in-human study characterized the safety, tolerability, and efficacy of SMK Therapy in subjects with advanced metastatic cancer. Methods All subjects (n = 30) received SMK Therapy for an initial 6 week Cycle (5 days on, 2 off per week) and continued if well tolerated. Safety signals, clinical response, overall survival, progression free survival (PFS), and quality of life changes were assessed. Results The most common drug related adverse events were hyperpigmentation and rash. All drug related adverse events were mild to moderate in intensity. Following treatment with SMK Therapy, 4 subjects achieved complete response, 6 partial response, and 17 stable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (total clinical benefit 90%). Responses were observed within 6 weeks, and continued to improve, with 3 complete and 3 partial responders achieving best response after at least 3.2 months. Durable stable disease was observed, lasting a median duration of 11 months (range 1-31 months). Median overall survival for all subjects was 29.8 months, and median PFS was 13 months. Following 6 weeks of treatment, most (83.3%) subjects showed an improvement in Eastern Cooperative Oncology Group (ECOG) score and an improvement in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ 30) global health status (baseline 61.2 ± 25.0; end of Cycle 1 80.7 ± 14.7; n = 29; p < 0.001). Conclusions The results of this study support continued development of SM-88.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melaninas/uso terapêutico , Neoplasias/tratamento farmacológico , Fenitoína/uso terapêutico , Sirolimo/uso terapêutico , alfa-Metiltirosina/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Exantema/induzido quimicamente , Feminino , Humanos , Hiperpigmentação/induzido quimicamente , Masculino , Melaninas/efeitos adversos , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Fenitoína/efeitos adversos , Projetos Piloto , Qualidade de Vida , Sirolimo/efeitos adversos , Análise de Sobrevida , alfa-Metiltirosina/efeitos adversosRESUMO
OBJECTIVE: To evaluate a new device for obtaining endometrial biopsies which combines global endometrial disruption using a brush with a built-in suction process. STUDY DESIGN: Endometrial biopsies were collected, using the GDP-Tao device, from fresh uteri hysterectomy specimens after completion of surgery. Results were compared to final hysterectomy pathology. Specificity and sensitivity and positive and negative predictive values were calculated. RESULTS: Based on a sample size calculation, 42 patients were included in this study. Endometrial tissue adequate for diagnosis was obtained in 93% (39/42) of biopsies. Classifying atypia as a positive result, the sensitivity of the new device was 96% (23/24), with specificity of 87% (13/15). The positive predictive value was 92% (23/25) and the negative predictive value, 93% (13/14). There were 2 nondiagnostic (ND) samples from GDP-Tao with final pathology of benign endometrium. One specimen was ND on both GDP-Tao and final pathology due to absence of tissue after prior endometrial ablation. When stratified by uterine size, benign or malignant, the results were similar. CONCLUSION: Our validation study showed encouraging results for the GDP-Tao, which combines tissue disruption and aspiration into a single process. The device provides a reliable means of obtaining adequate samples to accurately detect endometrial cancer with a high negative and positive predictive value.
Assuntos
Assistência Ambulatorial , Biópsia/métodos , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/instrumentação , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
CONTEXT: Uterine transplantation (UTx). OBJECTIVE: To explore patients' knowledge of and attitudes toward UTx before and after a short educational intervention via a video and question and answer (Q&A) session. DESIGN: Large, in-depth survey investigating patients' motivations, aims, and beliefs on UTx. SETTING: Imperial College London. PARTICIPANTS: Women diagnosed with absolute uterine factor infertility (AUFI) who were seeking information on UTx and had already volunteered to participate in the study. INTERVENTION: A semistructured interview involving a brief baseline questionnaire before a Q&A session and a 20-minute video exploring the main risks and benefits for UTx. MAIN OUTCOME MEASURES: Attitudes of self-referred patients with AUFI toward UTx before and after education focusing on UTx. Rank order of importance of key UTx-related issues. RESULTS: Forty women were interviewed. Following the video presentation and Q&A session, 97.5% (n = 39) would undergo UTx ahead of surrogacy and adoption in full knowledge that the latter 2 options would be ultimately safer for their own well-being and the fact that the graft could fail even prior to conception. All felt that UTx should take place, and 92.5% saw UTx as achievable. CONCLUSION: The study demonstrates a keen interest in UTx, partly because other options seem difficult to access. It is worth noting that people appear to be distancing themselves from the risk. This requires careful assessment in any clinical program. This study is the first to demonstrate a qualitative relationship between patients with AUFI and their curiosity and desire for UTx. It paves the way for forming the introduction into the psychological assessment of a potential patient.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Infertilidade Feminina/psicologia , Transplante de Órgãos/psicologia , Doenças Uterinas/psicologia , Útero/transplante , Transtornos 46, XX do Desenvolvimento Sexual/complicações , Transtornos 46, XX do Desenvolvimento Sexual/psicologia , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Adulto , Anormalidades Congênitas/psicologia , Anormalidades Congênitas/cirurgia , Feminino , Humanos , Histerectomia , Infertilidade Feminina/etiologia , Infertilidade Feminina/cirurgia , Pessoa de Meia-Idade , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/cirurgia , Reino Unido , Doenças Uterinas/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To investigate, develop and evaluate anatomical, surgical and anastomotic aspects necessary for a successful uterine transplant in a large-animal model. DESIGN: Sheep model; longitudinal study involving five ewes. SETTING: Royal Veterinary College, London, UK. POPULATION: Five ewes of proven fertility. METHODS: The uterine allograft along with the internal iliacs, and uterine arterial and venous tree all intact were harvested en bloc. An end-to-side anastomosis was performed between the external iliac vessels and the internal iliac vessels of the graft using 6-0 polypropylene. Successful reperfusion of the graft was initially judged by the color shift of the uterus during reperfusion. Blood flow past the venous and arterial anastomotic sites was also ensured by visual inspection, together with pulse oximetry and multispectral imaging. MAIN OUTCOME MEASURES: Operative details (retrieval, ischemic, clamping, reperfusion and recipient hysterectomy duration); physiological profiles; gross morphology and histopathology. RESULTS: Five autotransplants were performed. One procedure was abandoned because of the inappropriate size of sheep model. Another procedure was halted because the animal suffered from respiratory failure in the immediate intra-operative period. Three transplants were completed. In those, at least two of four possible anastomoses were finished and the grafted uteri demonstrated immediate perfusion and appropriate viability 45 min post-operatively. CONCLUSIONS: Internal to external iliac vessel anastomoses are an acceptable surgical technique that should be applied in a human model to ensure adequate subsequent uterine perfusion.
Assuntos
Anastomose Cirúrgica/métodos , Artéria Ilíaca/cirurgia , Modelos Animais , Útero/transplante , Animais , Feminino , Estudos Longitudinais , Carneiro Doméstico , Transplante Autólogo , Resultado do Tratamento , Útero/irrigação sanguíneaRESUMO
The treatment of early stage cervical malignancy in a pregnant patient remains a challenge. We report the successful application of a vaginal radical trachelectomy (VRT) during pregnancy to treat a patient diagnosed with early stage cervical cancer and subsequently review the published work. A 22-year-old female diagnosed at the gestational age of 17 weeks with International Federation of Gynecology and Obstetrics stage IB1 squamous cell cervical carcinoma was treated with VRT at 19(+5) weeks. At 36 weeks, the patient underwent a scheduled cesarean section. A healthy male infant was delivered with a weight of 2795 g. After 13 months of follow-up, the patient is doing well with no evidence of recurrent disease.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Complicações Neoplásicas na Gravidez/cirurgia , Traquelectomia , Neoplasias do Colo do Útero/cirurgia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Resultado da Gravidez , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
CONTEXT: Currently, the only 2 options that women with absolute uterine factor infertility have for managing their infertility are surragocy or adoption. These women may also benefit from a possible future third option: uterine transplant. OBJECTIVE: To investigate the opinions and views of UK health care professionals toward uterine transplant and rank issues related to uterine transplant by importance in order to make uterine transplant transparent and understandable to colleagues. DESIGN: Large, in-depth survey investigating health care professionals' opinions on uterine transplant. SETTING: Analysis done at Imperial College London. PARTICIPANTS: UK transplant professionals (surgeons, nurses, operating room staff, and donor coordinators) and obstetricians and gynecologists (trainees, members, and fellows of the Royal College of Obstetricians and Gynaecologists). INTERVENTION: Questionnaires were given out at hospital grand rounds, trainee teaching days, and conferences (national and international). MAIN OUTCOME MEASURES: Should uterine transplant take place? Is uterine transplant achievable? What is the rank order of importance of key issues related to uterine transplant? RESULTS: The study had 528 participants. With respect to overall support for uterine transplant and as a possible future therapeutic option for absolute uterine factor infertility, 93.8% (n=495) thought that uterine transplant should take place if considered appropriate medically, surgically, and ethically and 57.2% (n=302) thought it was an achievable objective. Issues related to immunology of uterine transplant and pregnancy after uterine transplant were unanimously thought of as most important. More effort is required to educate health care professionals about all aspects of uterine transplant.
Assuntos
Atitude do Pessoal de Saúde , Infertilidade Feminina/cirurgia , Útero/transplante , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Inquéritos e Questionários , Reino UnidoRESUMO
PURPOSE: The objective of this study was to report the results of in vitro chemoresponse analysis of primary, metastatic, and recurrent human cervical cancers. METHODS: There were 557 tumor specimens submitted for testing from August 2006 to June 2010. Single agents tested were cisplatin, carboplatin, paclitaxel, docetaxel, epirubicin, fluorouracil, 4-hydroxy ifosfamide (active metabolite of ifosfamide), SN-38 (active metabolite of irinotecan), topotecan, and vinorelbine. Doublets tested were carboplatin/paclitaxel and cisplatin/topotecan. Tumor response was determined from dose-response curves. Results were scored as responsive, intermediate, or nonresponsive. Chemoresponse was reported as the combined responsive and intermediate results. RESULTS: Three hundred fifty-three (63.4%) of 557 submitted specimens were successfully assayed. Confirmation of histology and tumor status (primary, metastatic, or recurrent) was available for 273 specimens. The chemoresponse of the most active agents in primary cancers (n = 151) was 75% for SN-38, 71% for 4-hydroxy ifosfamide, 62% for topotecan, and 73% for carboplatin/paclitaxel. The chemoresponse of metastatic cancers (n = 66) was 54% for SN-38, 51% for 4-hydroxy ifosfamide, 44% for epirubicin, and 53% for carboplatin/paclitaxel. The chemoresponse for recurrent cancers (n = 56) was 44% for epirubicin, 41% for 4-hydroxy ifosfamide, 39% for vinorelbine, 39% for paclitaxel, 36% for topotecan, 46% for carboplatin/paclitaxel, and 35% for cisplatin/topotecan. The overall chemoresponse was greater in primary cancers (58%) than in recurrent cancers (35%) (P < 0.0001). CONCLUSIONS: In vitro chemoresponse analysis of cervical cancer biospecimens is feasible. Chemoresponse results are variable depending on tumor status. Clinical studies of assay-directed therapy should be developed.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/secundário , Carcinoma de Células Escamosas/secundário , Feminino , Humanos , Técnicas In Vitro , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Fertility preservation techniques are a growing area of research as more women in the reproductive age group develop gynaecologic cancers. We report here a novel technique of fertility preservation used in the treatment of a patient with borderline ovarian tumour. CASE: A 29-year-old woman with stage I borderline ovarian tumour was referred to our tertiary level hospital. She had a history of infertility and requested fertility preservation be considered in treatment decisions. We performed bilateral laparoscopic partial decortication of the ovaries, and the patient successfully conceived spontaneously following the procedure. CONCLUSION: Fertility-preserving surgery should be an option for young women with borderline ovarian tumours who wish to retain fertility. Removing abnormal ovarian tissue may restore fertility. The laparoscopic approach is safe and feasible for these patients.
Contexte : Les techniques de préservation de la fertilité constituent un champ de recherche en évolution, de plus en plus de femmes en âge de procréer étant atteintes de cancers gynécologiques. Nous nous penchons sur une technique novatrice de préservation de la fertilité utilisée dans le cadre de la prise en charge d'une patiente présentant une tumeur ovarienne à la limite de la malignité. Cas : Une femme de 29 ans présentant une tumeur ovarienne à la limite de la malignité de stade I a été orientée vers notre hôpital de niveau tertiaire. Elle présentait des antécédents d'infertilité et souhaitait que la préservation de la fertilité soit prise en considération dans le cadre du processus de prise de décision quant au traitement. Nous avons pratiqué une décortication laparoscopique bilatérale partielle des ovaires et la patiente a été en mesure de connaître une grossesse spontanée à la suite de l'intervention. Conclusion : La chirurgie visant à préserver la fertilité devrait constituer une solution possible pour les jeunes femmes présentant une tumeur ovarienne à la limite de la malignité qui souhaitent demeurer fertiles. L'excision de tissus ovariens anormaux pourrait permettre de rétablir la fertilité. L'approche laparoscopique est sûre et praticable dans le cas de ces patientes.
Assuntos
Cistoadenofibroma , Preservação da Fertilidade/métodos , Neoplasias Ovarianas , Ovariectomia/métodos , Adulto , Cistoadenofibroma/patologia , Cistoadenofibroma/cirurgia , Feminino , Humanos , Laparoscopia/métodos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Ovário/cirurgia , Gravidez , Resultado da Gravidez , Resultado do TratamentoRESUMO
AIM: To see if: (i) a large vessel aortocaval vascular patch technique may bring about long-term graft survival after allogeneic uterine transplantation (UTn) in a rabbit model; and (ii) fertility can be achieved following natural mating post-allogeneic UTn. METHODS: Allogeneic uterine cross transplantations were performed in New Zealand white rabbits using an aortocaval macrovascular patch harvested as part of the uterine allograft. Five rabbit recipients received a uterine graft from five unrelated donor rabbits. All female rabbits were unrelated and were of proven fertility with at least one previous litter each. Tacrolimus was administrated for immunosuppression post-transplant. Natural mating was attempted if long-term survival had been achieved. The main outcome measures were: (i) long-term recipient survival; (ii) long-term adequate uterine perfusion; and (iii) successful pregnancy post-UTn. RESULTS: All five recipient animals survived the surgery with satisfactory immediate postoperative recovery. Recipients 1, 2 and 4 died within the first 4 postoperative days. Both long-term survivors failed to conceive following introduction of a proven male breeder despite evidence of mating. Necropsy at 9 and 11 months showed a lack of patency of uterine cornua at the point of anastomosis, albeit a small uterus in recipient 3 and a reddish brown amorphous material at the site of the transplanted uterus in recipient 5. CONCLUSION: We have demonstrated the feasibility of uterine allotransplantation using a macrovascular patch technique, but could not demonstrate conception because of blocked cornua. To address this, we propose using embryo transfer techniques in order to achieve conception.
Assuntos
Útero/transplante , Dispositivos de Oclusão Vascular/efeitos adversos , Animais , Estudos de Viabilidade , Feminino , Fertilidade , Sobrevivência de Enxerto , Coelhos , Transplante Homólogo , Útero/irrigação sanguíneaRESUMO
Cell-based therapeutic cancer vaccines use autologous patient-derived tumor cells, allogeneic cancer cell lines or autologous antigen presenting cells to mimic the natural immune process and stimulate an adaptive immune response against tumor antigens. The primary objective of this study is to perform a systematic literature review with an embedded meta-analysis of all published Phase 2 and 3 clinical trials of cell-based cancer vaccines in human subjects. The secondary objective of this study is to review trials demonstrating biological activity of cell-based cancer vaccines that could uncover additional hypotheses, which could be used in the design of future studies. We performed the systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final review included 36 studies - 16 single-arm studies, and 20 controlled trials. Our systematic review of the existing literature revealed largely negative trials and our meta-analysis did not show evidence of clinical benefit from cell-based cancer-vaccines. However, as we looked beyond the stringent inclusion criteria of our systematic review, we identified significant examples of biological activity of cell-based cancer vaccines that are worth highlighting. In conclusion, the existing literature on cell-based cancer vaccines is highly variable in terms of cancer type, vaccine therapies and the clinical setting with no overall statistically significant clinical benefit, but there are individual successes that represent the promise of this approach. As cell-based vaccine technology continues to evolve, future studies can perhaps fulfill the potential that this exciting field of anti-cancer therapy holds.
Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Antígenos de Neoplasias , Imunidade AdaptativaRESUMO
A group of experts gathered in Indianapolis in December 2011 to address lingering concerns related to uterus transplantation (UTn). They represent a multi-national group of four research teams who have worked for over 15 years on bringing UTn to reality for patients. Presented here are a set of parameters that must be considered in order for UTn to become an acceptable procedure in the human setting. UTn has been proposed as a potential solution to absolute uterine factor infertility (AUFI). Causes of AUFI include congenital uterine factors (i.e. absence or malformation) or acquired uterine factors (e.g. hysterectomy for uncontrollable hemorrhage) rendering a woman 'unconditionally infertile'. Current estimates are that in the USA, up to 7 million women with AUFI may be appropriate candidates for UTn. As a result of a first human attempt in 2000, investigators have responded with a plethora of publications demonstrating successful UTn attempts, including pregnancies, in various autogeneic, syngeneic and allogeneic animal models. Before UTn can become an accepted procedure, it must satisfy defined criteria for any surgical innovation, i.e. research background, field strength and institutional stability. Equally important, UTn must satisfy accepted bioethical principles (respect for autonomy, beneficence, non-maleficence and justice) and their application (informed consent, appropriate assessment of risk and benefit and fair selection of individuals). Furthermore, we believe that a defined number of transplants should not be exceeded worldwide without a successful term delivery, to minimize proceeding in futility using current techniques. Even if UTns were to become relatively common, the following research objectives should be continuously pursued: (i) additional pregnancies in a variety of large animal/primate models (to search for unanticipated consequences), (ii) continuous assessment of women diagnosed with AUFI regarding UTn, (iii) continuous assessment using 'borrowed' psychological tools from transplant centers, adoption agencies and assisted reproductive technology centers with potential recipients and (iv) continuous careful ethical reflection, assessment and approval.
Assuntos
Infertilidade Feminina/cirurgia , Útero/transplante , Consenso , Feminino , Humanos , Transplante de Órgãos/ética , Transplante de Órgãos/psicologia , Técnicas de Reprodução Assistida/ética , Técnicas de Reprodução Assistida/psicologia , Estados UnidosRESUMO
Ascites in epithelial ovarian cancer (EOC) promotes tumor development by mechanisms that are incompletely understood. Lysophosphatidic acid (LPA), a major tumor-promoting factor in EOC ascites, is an enzymatic product of autotaxin (ATX) and phospholipase A(2) (PLA(2))enzymes. The contribution of PLA(2) activities to ovarian tumorigenesis was investigated. The quantitative measurement of PLA(2) activities in ascites and tissues, as well as assay conditions selective for PLA(2) subtypes, were optimized and validated. PLA(2) activities correlated with tumor-promoting activates in cell-based and in vivo assays. High activities consistent with both cytosolic and calcium-independent PLA(2) were found in human EOC ascites for the first time. Elevated PLA(2) and ATX activities were also observed in EOC compared to benign tumors and normal tissues. Cell-free and vesicle-free (S4) human EOC ascites potently promoted proliferation, migration, and invasion of human EOC cells in a PLA(2)-dependent manner. LPA mediated a significant part of the cell-stimulating effects of ascites. S4 ascites stimulated tumorigenesis/metastasis in vivo, and methyl arachidonyl fluorophosphonate was highly effective in inhibiting EOC metastasis in mouse xenograft models. PLA(2) activity was found in conditioned media from both EOC cells and macrophages. Collectively, our work implies that PLA(2) activity is a potential marker and therapeutic target in EOC.
Assuntos
Neoplasias Epiteliais e Glandulares/fisiopatologia , Neoplasias Ovarianas/fisiopatologia , Animais , Ácidos Araquidônicos/uso terapêutico , Ascite/patologia , Ascite/fisiopatologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Lisofosfolipídeos , Camundongos , Transplante de Neoplasias , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , Organofosfonatos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Fosfolipases A2 Secretórias , Diester Fosfórico Hidrolases/metabolismo , Transplante HeterólogoRESUMO
We describe an exciting and novel surgical option, which may be used to treat formerly unresectable masses. This process is commonly referred to as autotransplantation (AuTn), and it combines the advances in transplant medicine and applies them to surgical oncology. The idea behind AuTn is the removal of the cancerous organ(s) to allow complete anatomic resection of the tumor mass, with consequent anastomotic reimplantation or AuTn of the now macroscopically tumor-free organ back into the patient. Autotransplantation has been used to remove large fibromatosis and desmoid tumors as well as malignant tumors. Our belief is that using lessons learned from the field of transplantation, AuTn can be applied in gynecologic oncology.
Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Transplante de Órgãos , Feminino , Humanos , Transplante AutólogoRESUMO
OBJECTIVE: Invasive cervical cancer is one of the most common cancers, with 500,000 new cases diagnosed annually. Fertility preservation has become an important component of the overall quality of life of many cancer survivors. Expert opinion has suggested that fertility-sparing surgery should be limited to those patients diagnosed with cervical cancer less than 2 cm in diameter. Our objective was to report our abdominal radical trachelectomy (ART) experience in the opposite group of patients-those with a cervical cancer more than 2 cm in diameter. METHODS: Between 1999 and 2006, a total of 45 patients with cervical carcinoma at International Federation of Gynecology and Obstetrics stage IB1-IB2 measuring more than 2 cm in diameter underwent fertility-sparing ART and pelvic lymphadenectomy at the 3 institutions where the authors are based (Budapest, Hungary; London, United Kingdom; New York, United States). They were followed up for more than 5 years. RESULTS: For 69% of patients (n = 31), completed ART was considered to have been curative, and no adjuvant treatment was advised. Of those patients, 93.5% (n = 29) were alive at the time of follow-up. Thirty-one percent of patients (n = 14) underwent immediate completion of radical hysterectomy. Three of 8 patients who wished to fall pregnant delivered healthy neonates. CONCLUSIONS: The 5-year survival rate (93.5%) for this case series is equal (or better) to rates reported in the literature for patient treated with radical hysterectomy. Our survival data seem to support the hypothesis that ART is a safe treatment option for patients with invasive cervical cancer lesions of more than 2 cm.
Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Colo do Útero/cirurgia , Histerectomia , Recidiva Local de Neoplasia/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Colo do Útero/patologia , Feminino , Fertilidade , Seguimentos , Humanos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Gravidez , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
INTRODUCTION: The aim of this study was to report a case of cervical cancer stage IB2 treated with neoadjuvant chemotherapy, followed by simultaneous robotic-assisted radical trachelectomy and reversal of tubal sterilization. CASE DESCRIPTION: This case occurred in a university hospital involving a 31-y-old woman with stage IB2 cervical cancer treated using neoadjuvant chemotherapy, robotic surgery, and tubal anastomosis to determine cancer disease status and achieve restoration of tubal patency. DISCUSSION: A successful radical trachelectomy with patent tubes was done bilaterally. Cancer and fertility procedures can be simultaneously implemented and achieved.
Assuntos
Antineoplásicos/uso terapêutico , Histerectomia/métodos , Estadiamento de Neoplasias , Robótica , Esterilização Tubária/efeitos adversos , Neoplasias do Colo do Útero/terapia , Adulto , Biópsia , Colo do Útero/cirurgia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologiaRESUMO
In the last two decades, great strides have been made to treat cancer while sparing fertility for young women. This is at least partly in response to changing demographics, including delayed childbearing and fewer historically traditional couples. The trachelectomy has become emblematic in this endeavor. With comparable outcomes to hysterectomy and successful conceptions, trachelectomy utilization has increased over time. It is now a standard of care for many situations. While there are several approaches, (vaginal, laparoscopic, and robotic), the abdominal trachelectomy allows surgeons to overcome several limitations, such as patient anatomy, surgical experience, and resources (i.e. no robot) to provide women everywhere this revolutionary operation. In this chapter, we outline surgical techniques, outcomes, and other aspects of the abdominal trachelectomy.
Assuntos
Preservação da Fertilidade , Traquelectomia , Neoplasias do Colo do Útero , Feminino , Fertilidade , Humanos , Histerectomia , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVE: To assess the contemporary incidence of cancers using American Samoa as a learning set for insights into similar populations. METHODS: A retrospective observational analysis of de-identified data held in public-access databases (2004-2014) and data on uterine cancer from a hospital, both in American Samoa (2015-2016). RESULTS: There were 341 new cases of cancer in 2004-2014 (111 per 100 000 women/year), including breast (20.2%), uterine (19.4%), and cervical (5.0%); and 287 in 2011-2015 (103 per 100 000 women/year), including uterine (24.0%), breast (18.5%), and cervical (5.2%). Uterine cancer increased from 21.4 to 60.3 per 100 000 women/year, becoming the most common cancer in American Samoa. In 2011-2015, the incidence-rate ratio of uterine cancer to other cancers in American Samoa was 1.3-, 3.8-, 4.6-, 7.7-, and 23-fold higher than breast, colon, cervical, ovarian, and lung cancer, respectively. Among the most recent cases (n=33), median age was 55 years (10 [30.3%] <50 years), median BMI was 38.2; and 11 (33.3%) cases had grade 3 histology. CONCLUSION: The pattern of cancers in American Samoa differs from that in the US mainland. The findings reflect significant changes in cancer incidence. Cancer control programs should evaluate the potential of uterine screening in accordance with their community's needs and characteristics.