ABSTRACT
OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of secondary CRS and chemotherapy in comparison to chemotherapy alone for women with platinum-sensitive recurrent epithelial ovarian cancer.
Subject(s)
Carcinoma, Ovarian Epithelial , Cytoreduction Surgical Procedures , Neoplasm Recurrence, Local , Ovarian Neoplasms , Humans , Female , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/surgery , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Neoplasm Recurrence, Local/drug therapy , Cytoreduction Surgical Procedures/methods , Systematic Reviews as Topic , Randomized Controlled Trials as Topic , Combined Modality Therapy/methods , Antineoplastic Agents/therapeutic useABSTRACT
The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitro models of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/ß-catenin signaling and engineer endogenous WNT/ß-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/ß-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease.
Subject(s)
Fallopian Tubes , beta Catenin , Female , Humans , beta Catenin/metabolism , Fallopian Tubes/metabolism , Transcriptome/genetics , Stem Cells/metabolism , Wnt Signaling Pathway , Organoids/metabolism , Wnt Proteins/genetics , Wnt Proteins/metabolism , Frizzled Receptors/metabolismABSTRACT
Open abdominal surgery evolved around two incisions, vertical and transverse incisions. Transverse incisions are associated with less postoperative morbidities but offer limited access. Vertical incisions offer better access but are associated with more complications. We describe here a hybrid incision, transverse-vertical incision that offers adequate exposure for complex lower abdominopelvic surgery while overcoming the limitations and morbidities associated with midline and transverse incisions.
Subject(s)
Surgical Wound , Humans , Postoperative PeriodABSTRACT
Adamantinoma is a rare low-grade malignancy of the appendicular skeleton with unclear histogenesis. We present the case of a 65-year-old woman with known recurrent and metastatic right tibial disease despite clear resection margins. On further investigation, a positron emission tomography-CT scan identified a primary breast lesion and an 11 cm mass in the right iliac fossa of suspected ovarian malignancy amenable to surgical resection. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and resection of a retroperitoneal mass arising from the pelvic sidewall encompassing the iliac vasculature. The patient made an uneventful recovery with histology confirming disease metastasising to the pelvis. Currently, clinical management guidelines are not available. We present an overview of adamantinoma and highlight a previously undocumented gynaecological oncology surgical approach to this novel disease location. Regarding metastases, we acknowledge the challenges of investigation pertaining to disease site and origin as well as a paucity of recommendations for surveillance and follow-up.
Subject(s)
Adamantinoma , Ovarian Neoplasms , Adamantinoma/diagnostic imaging , Adamantinoma/surgery , Aged , Female , Humans , Hysterectomy , Ovarian Neoplasms/surgery , Pelvis , Salpingo-oophorectomyABSTRACT
BACKGROUND: The prevalence of placenta accreta spectrum is rising worldwide. The severe end of the spectrum where the placenta has invaded other organs is fortunately rare, however, few surgical techniques for such a complex hysterectomy have been described in the literature. OBJECTIVE: This study aimed to describe a stepwise, systematic technique for radical cesarean hysterectomy for placenta accreta spectrum to investigate outcomes for women with severe, invasive placenta accreta spectrum who were hysterectomized using this technique. STUDY DESIGN: This was a retrospective cohort study undertaken at a large UK tertiary referral center. A total of 24 cases of elective primary cesarean hysterectomy with a confirmed intrapartum diagnosis of severe percreta (Federation of Gynecology and Obstetrics grades 3b and 3c) were identified between 2011 and 2020. Among those cases, 16 had standard care (surgical technique dependent on surgeon's preference), and 8 had a radical peripartum hysterectomy using the Soleymani-Alazzam-Collins technique as described. Nonparametric testing was used because of sample size. RESULTS: The Soleymani-Alazzam-Collins technique resulted in significantly less blood loss (P=.032), more transverse incisions (P=.009), and less intensive care unit admissions (P=.046). Furthermore, there was no significant difference in theater time. CONCLUSION: The Soleymani-Alazzam-Collins technique demonstrated a significant improvement in outcomes for women with severe placenta accreta spectrum, without increasing surgical time.
Subject(s)
Blood Loss, Surgical , Cesarean Section/methods , Hysterectomy/methods , Intensive Care Units/statistics & numerical data , Operative Time , Placenta Accreta/surgery , Adult , Female , Humans , Postoperative Complications/epidemiology , Pregnancy , Retrospective Studies , Severity of Illness Index , Surgical OncologyABSTRACT
Gastrointestinal stromal tumours (GISTs) are rare - and rectovaginal extragastrointestinal stromal tumours (RV-EGISTs) even rarer. We share a case of RV-EGIST, complemented by high-quality radiological and surgical images. A review of current literature pertaining to RV-EGIST is also included. Our case report highlights the diagnostic challenge presented by extragastrointestinal stromal tumours. Differentiated from overlapping pathologies only by targeted application of immunohistopathology and cytogenetics, the inclusion of RV-EGIST in the differential diagnosis of a rectovaginal tumour is essential to making this correct diagnosis. Primary surgery is the treatment of choice for RV-EGIST if complete cytoreduction can be achieved, combined with adjuvant tyrosine kinase inhibitor (TKI) therapy for those with high-risk features to further reduce rates of future recurrence.
Subject(s)
Gastrointestinal Stromal Tumors , Soft Tissue Neoplasms , Diagnosis, Differential , Fascia , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/surgery , Humans , Neoplasm Recurrence, LocalABSTRACT
PURPOSE: Struma ovarii is rare, accounting for 0.3-1% of ovarian tumours. Malignant transformation may occur, most often into papillary thyroid carcinoma. There is a paucity of data pertaining to malignant struma ovarii. This paper shares a decade of experience of a single institution in the management of this rare ovarian cancer, exploring the characteristics of this tumour and suggesting a standardised approach to treatment and follow-up. METHODS: All patients treated for malignant struma ovarii within a large cancer centre over one decade were identified and data collected retrospectively on presentation, diagnosis, management, follow-up and survival outcomes. A literature review was also undertaken. RESULTS: Eleven cases of malignant struma ovarii were managed in the Oxford Cancer Centre between 2010 and 2019, 6 of which were of papillary thyroid carcinoma sub-type. No cases were correctly diagnosed pre-operatively. All patients had stage I disease and were managed surgically-but with variation in radicality. Patients identified as high-risk based on final histopathology underwent additional thyroidectomy and radio-active iodine ablation therapy. One case of synchronous malignancy of the thyroid gland proper was identified. No disease recurrence occurred. CONCLUSION: Malignant struma ovarii present a diagnostic challenge. Multi-disciplinary team (MDT) input is essential. Unilateral salpingo-oophrectomy may be adequate if stage I; reserving more radical surgery for advanced disease. Histopathological risk-stratification should be used to identify those most likely to benefit from adjuvant thyroid-targeting therapies. Patients require follow-up, anticipating an overall good prognosis.
Subject(s)
Combined Modality Therapy/methods , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Struma Ovarii/mortality , Struma Ovarii/pathology , Adult , Aged , Female , Humans , Middle Aged , Retrospective Studies , Survival Analysis , Time FactorsABSTRACT
BACKGROUND: Several studies have demonstrated the feasibility and role of bulky cardiophrenic lymph nodes (CPLNs) resection during primary debulking surgery (PDS) for stage IV ovarian cancer (OC). However, no studies, to date, investigated the accuracy and feasibility of CPLNs assessment and removal during interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: A retrospective analysis of consecutive stage IV OC patients who underwent NACT followed by IDS with CPLNs assessment and/or resection from July 2017 to June 2018. Bulky CPLNs were considered for excision when a full-thickness diaphragmatic resection was required in order to achieve complete tumour resection. RESULTS: A total of 21 ovarian cancer stage IV patients treated with NACT followed by IDS were identified. Seven (33.3%) patients underwent CPLNs resection due to bulky appearance of the CPLNs at the intraoperative palpation. The final histological examination of the CPLNs reported metastatic disease in four (57%) of seven patients. Complete cytoreduction without residual disease was achieved in five cases (71.4%) while in two case (28.6%) optimal cytoreduction was performed. Intra-operative surgical complications occurred in one patient. One patient had a major postoperative complication (Clavien-Dindo 3). Two cases of postoperative cardiac arrhythmia were observed. CONCLUSIONS: CPLNs intraoperative assessment is less accurate during IDS compared to previous PDS studies. CPLNs removal during IDS after NACT for stage IV OC could be safely performed to achieve a complete resection.
Subject(s)
Cytoreduction Surgical Procedures , Ovarian Neoplasms , Cytoreduction Surgical Procedures/adverse effects , Feasibility Studies , Female , Humans , Lymph Nodes/surgery , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Retrospective StudiesABSTRACT
BACKGROUND: Elderly ovarian cancer (OC) patients are more likely to be managed suboptimally, with worse clinical outcomes as a result. Strategies to decrease morbidity are lacking.Methodology: Consecutive patients with advanced stage OC (IIIC-IV) who were managed in our center between January 2016 and July 2018 were retrospectively analyzed. All patients underwent neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) according to our institution protocol. We divided patients into two groups: Group 1 (age ≥ 70 years) and Group 2 (age < 70 years). The primary outcome of the study was assessment of peri-operative morbidity amongst two groups. RESULTS: A total of 153 patients were referred during the study period. 114 patients underwent IDS after NACT (74.5%), 46 in Group 1 and 68 in Group 2. Elderly patients were more likely to receive more than three cycles of NACT prior to IDS compared to younger patients (39% vs. 19%, p = 0.03). Elderly patients were more frequently subjected to Cardiopulmonary Exercise Testing (CPET) as pre-operative assessment (63% vs. 27%, p = 0.002). Optimal/complete resection was achieved in all patients in Group 1 (100%) and in 97% of patients in Group 2. With the exception of higher postoperative cardiac arrhythmias in Group 1 (11% vs. 1%, p = 0.04), no significant differences in 30-day morbidity were observed. No 90-day death in both groups was registered. CONCLUSION: Older age should not preclude clinicians from offering ultra-radical resection to patients with advanced OC after NACT. In our series, elderly patients received the same treatment with similar outcomes to the younger group. Clinicians should be encouraged to use CPET for patients' selection following NACT.
Subject(s)
Cytoreduction Surgical Procedures , Ovarian Neoplasms , Aged , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures/adverse effects , Female , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Retrospective StudiesABSTRACT
High-grade endometrial cancers (ECs) are an aggressive subset of ECs accounting for 70-80% of EC-related deaths. Currently, staging surgery, together with chemotherapy or radiotherapy, is the primary treatment strategy for these cancers. The widespread use of next-generation sequencing has led to a refined understanding of EC's genomics with important information for diagnosis and therapy for individual patients (precision medicine). However, advances in the genomics assessment of high-grade tumors have been slower due to their lower incidence than low-grade EC. This article will briefly introduce the current state of knowledge of the genomics of G3 endometrioid EC, serous uterine cancer, clear cell uterine carcinoma and uterine carcinosarcoma and discuss its implications for diagnosis and targeted therapy.
Subject(s)
Carcinoma/pathology , Endometrial Neoplasms/pathology , Carcinosarcoma/pathology , Female , Histological Techniques , Humans , Molecular Diagnostic Techniques , Neoplasm GradingABSTRACT
The evolution of multidisciplinary team-based care for women with placenta accreta spectrum disorder has delivered stepwise improvements in clinical outcomes. Central to this overall goal is the ability to limit blood loss at surgery. Placement of inflatable balloons within the pelvic arteries, most commonly in the anterior divisions of the internal iliac arteries, became popular in many centers, at the expense of prolonging surgical care and with attendant risks of vascular injury. In tandem, the need to expose pelvic sidewall anatomy to safely identify the course of the ureters re-popularized the alternative strategy of ligating the same anterior divisions of the internal iliac arteries. With incremental gains in surgical expertise, described in 5 steps in this review, our teams have witnessed a steady decline in surgical blood loss. Nevertheless, a subset of women has the most severe form of placenta accreta spectrum, namely placenta previa-percreta. Such women are at risk of major hemorrhage during surgery from vessels arising outside the territories of the internal iliac arteries. These additional blood supplies, mostly from the external iliac arteries, pose significant risks of major blood loss even in experienced hands. To address this risk, some centers, principally in China, have adopted an approach of routinely placing an infrarenal aortic balloon, with both impressively low rates of blood loss and an ability to conserve the uterus by resecting the placenta with the affected portion of the uterine wall. We review these literature developments in the context of safely performing elective cesarean hysterectomy for placenta previa-percreta, the most severe placenta accreta spectrum disorder.
Subject(s)
Blood Loss, Surgical/prevention & control , Cesarean Section/adverse effects , Hysterectomy/adverse effects , Placenta Accreta/surgery , Placenta Previa/surgery , Balloon Occlusion , Cesarean Section/methods , Colpotomy , Female , Humans , Hysterectomy/methods , Iliac Artery/surgery , Ligation , Magnetic Resonance Imaging , Pregnancy , Risk Factors , Treatment OutcomeABSTRACT
OBJECTIVES: To assess the impact of multiple bowel resections on postoperative outcomes in stage IIIC-IV ovarian cancer (OC). METHODS: From the Oxford OC database we retrieved consecutive patients who underwent bowel resection between January 2009 and November 2017. Patients were divided into two groups: single bowel resection (SBR) and MBR (≥2 bowel resections). The following outcomes were compared between the two groups: 30-day related and not related morbidity to bowel surgery, bowel diversion rate and time to start/restart adjuvant chemotherapy. RESULTS: Thirty-five patients were in the MBR and 146 in the SBR group. The 30-day overall surgical-related complication and bowel specific complications rate was higher in MBR group than SBR group (54.3% vs. 23.9%, pâ¯<â¯0.001) and (25.7% vs. 10.5%, pâ¯=â¯0.035), respectively. The rate of bowel diversion was 97.7% in MBR vs. 26.7% in the SBR group (pâ¯=â¯0.021). Trend analysis showed a significant reduction in the rate of MBR after the introduction of NACT (p- for trend <0.001). CONCLUSIONS: Our data show that MBR during OC surgery is associated with a higher rate of overall and bowel specific complication compared to SBR. The introduction of NACT is associated with a reduced rate of MBR.
Subject(s)
Carcinoma, Ovarian Epithelial/surgery , Cytoreduction Surgical Procedures/methods , Digestive System Surgical Procedures/methods , Intestines/surgery , Ovarian Neoplasms/surgery , Aged , Carcinoma, Ovarian Epithelial/drug therapy , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures/adverse effects , Digestive System Surgical Procedures/adverse effects , Female , Humans , Middle Aged , Ovarian Neoplasms/drug therapy , Postoperative Complications/etiologyABSTRACT
OBJECTIVE: To ascertain the efficacy and safety of laparoscopic uterine artery occlusion (LUAO) during laparoscopic myomectomy (LM) on intra- and postoperative morbidity and to assess its impact on leiomyoma recurrence rates. DATA SOURCES: MEDLINE, Scopus, Web of Science, and Cochrane Database were searched for relevant references from inception until December 2018, in line with PRISMA guidelines. METHODS OF STUDY SELECTION: Two authors screened for study eligibility and extracted data. Randomized controlled trials (RCTs) and observational studies (OSs) comparing short- and long-term morbidity of LM with or without LUAO were included. The modified Jadad score and the methodologic index for nonrandomized studies were used to evaluate the quality of RCTs and OSs, respectively. TABULATION, INTEGRATION, AND RESULTS: Twelve studies encompassing 750 LM and 873 LUAO-LM cases were included in the meta-analysis. The studies were of moderate quality. LUAO-LM appears to significantly decrease intraoperative blood loss, postoperative hemoglobin drop, and blood transfusion rate. A trend toward shorter hospital length of stay was demonstrated, whereas no significant difference in operation duration was observed. The combined procedure seemingly contributes to lower recurrence rate. No LUAO-related complications were reported. Moderate to high heterogeneity was observed for few outcomes. CONCLUSION: This is the first meta-analysis to date to provide a convincing overview of efficacy and safety of LUAO-LM. Although a medium risk of bias warrants some caution with interpretation of the results, LUAO-LM seemingly improves intra- and postoperative outcomes in women with symptomatic leiomyomas.
Subject(s)
Laparoscopy/methods , Leiomyoma/surgery , Neoplasm Recurrence, Local/surgery , Uterine Artery/surgery , Uterine Myomectomy/methods , Uterine Neoplasms/surgery , Adult , Blood Loss, Surgical , Blood Transfusion , Female , Humans , Middle Aged , Observational Studies as Topic , Postoperative Period , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
BACKGROUND: This is the second update of a Cochrane review that was first published in 2009, Issue 1, . Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. OBJECTIVES: To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN. SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase in September 2008, February 2012, and January 2016. In addition, we searched online trial registers for protocols and ongoing trials. SELECTION CRITERIA: For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated versions of the review, we included only RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed using the random-effects model. MAIN RESULTS: We included seven RCTs (667 women) in this updated review. Most studies were at a low or moderate risk of bias and all compared methotrexate with actinomycin D. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) actinomycin D (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV actinomycin D (75 women), one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV actinomycin D (49 women), and one study compared eight-day IM MTX-FA with bi-weekly pulsed IV actinomycin D. One study contributed no data. Moderate-certainty evidence indicates that actinomycin D is probably more likely to lead to primary cure than methotrexate (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.57 to 0.75; six trials, 577 participants; I(2) = 26%), and first-line methotrexate treatment is probably more likely to fail than actinomycin D treatment (RR 3.55, 95% CI 1.81 to 6.95; six trials, 577 participants; I(2) = 61%; moderate-certainty evidence) Low-certainty evidence suggests that there may be little or no difference between methotrexate and actinomycin D treatment with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too inconsistent to be conclusive. Low-certainty evidence suggests that there may be little or no difference in the risk of severe adverse events (SAEs) between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%); however, the direction of effect favours methotrexate and more evidence is needed. Furthermore, evidence from subgroup analyses suggests that actinomycin D may be associated with a greater risk of SAEs than methotrexate (low-certainty evidence). We found no evidence on the effect of these treatments on future fertility. AUTHORS' CONCLUSIONS: Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low-risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN.
Subject(s)
Antineoplastic Agents/administration & dosage , Dactinomycin/administration & dosage , Gestational Trophoblastic Disease/drug therapy , Methotrexate/administration & dosage , Antineoplastic Agents/adverse effects , Case-Control Studies , Cohort Studies , Dactinomycin/adverse effects , Drug Administration Schedule , Female , Humans , Leucovorin/administration & dosage , Methotrexate/adverse effects , Pregnancy , Randomized Controlled Trials as Topic , Risk , Vitamin B Complex/administration & dosageABSTRACT
BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic. OBJECTIVES: To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to 16 Novemeber 2015. In addition, we searched online clinical trial registries for ongoing trials. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were included. DATA COLLECTION AND ANALYSIS: We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses. MAIN RESULTS: The search identified no RCTs; therefore we were unable to perform any meta-analyses. AUTHORS' CONCLUSIONS: RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5-FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.
Subject(s)
Drug Resistance, Neoplasm , Gestational Trophoblastic Disease/drug therapy , Neoplasm Recurrence, Local/drug therapy , Female , Humans , PregnancyABSTRACT
OBJECTIVE: To measure the long-term impact of surgical treatment for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of therapy. METHODS: Prospective, longitudinal, mixed-methods study. Twenty-three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF-36 and an electronic pelvic floor assessment questionnaire (ePAQ-PF) were administered at baseline (pre-treatment) and 3, 6, 9 and 12 months post-treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach. RESULTS: Mean age was 59.9 years (SD = 15.3; range = 23.8-86.6 yrs). Mean BMI was 30.0 (SD = 4.5; range = 24.4-38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre-treatment (p = < 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF-36 mental health scores at 12 months compared to women with early stage disease (p = 0.037). CONCLUSIONS: Surgery for vulval cancer has long-term implications which can be persistent 12 months post-treatment. High rates of morbidity relating to lymphoedema and sexual function re-enforce the need for specialist clinics to support women who suffer these complications. © 2015 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.
Subject(s)
Pelvic Floor , Quality of Life/psychology , Survivors/psychology , Vulvar Neoplasms/psychology , Adult , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , Middle Aged , Neoplasm Staging , Prospective Studies , Surveys and Questionnaires , Vulvar Neoplasms/surgery , Young AdultABSTRACT
PURPOSE: (1) To determine the impact of treatment and recovery on the health-related quality of life (HRQoL) of endometrial cancer (EC) patients. (2) To explore how treatment types and delivery affect HRQoL and invite suggestions for improvement. METHODS: Qualitative study. In-depth, semi-structured interviews at 3, 6, 9 or 12 months post-treatment were carried out with 22 women with stage IA to IVB EC who had undergone treatment at a tertiary referral centre for gynaecological cancers in Sheffield, UK. 21 were treated surgically and 4 received adjuvant treatment. Data were analysed using an inductive thematic approach. RESULTS: Four dominant themes emerged regarding the treatment pathway: pre-treatment concerns, experience during treatment, post-treatment and survivorship issues. Expectations and understandings of EC and its treatment were often inaccurate. Proper explanations eased anxiety but were uncommon. Laparoscopic surgery was welcomed where offered but did not necessarily influence coping ability. Instead, women evaluated treatment impacts against their expectations. Treatments affected women's physical abilities, self-perception and relationships resulting in re-evaluation of lifestyle. CONCLUSIONS: The impact of treatment upon HRQoL for women with EC differs from other gynaecological cancers. Better information provision would enhance coping ability. Coping methods and expectations appear to influence HRQoL more than treatment modality.
Subject(s)
Endometrial Neoplasms/therapy , Health Status , Quality of Life , Adaptation, Physiological , Adaptation, Psychological , Adult , Aged , Chemotherapy, Adjuvant , Combined Modality Therapy , Critical Pathways , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/psychology , Female , Follow-Up Studies , Humans , Interviews as Topic , Longitudinal Studies , Middle Aged , Qualitative Research , Radiotherapy, Adjuvant , Risk Assessment , Self Concept , Sickness Impact Profile , Survivors/psychology , Time Factors , Treatment Outcome , United KingdomABSTRACT
BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic. OBJECTIVES: To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were included. DATA COLLECTION AND ANALYSIS: We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses. MAIN RESULTS: The search identified no RCTs; therefore we were unable to perform any meta-analyses. AUTHORS' CONCLUSIONS: RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5-FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.
Subject(s)
Drug Resistance, Neoplasm , Gestational Trophoblastic Disease/drug therapy , Neoplasm Recurrence, Local/drug therapy , Female , Humans , PregnancyABSTRACT
BACKGROUND: This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. OBJECTIVES: To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN. SEARCH METHODS: In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review. SELECTION CRITERIA: For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials. MAIN RESULTS: We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women).Overall, dactinomycin was associated with significantly higher rates of primary cure than methotrexate (five studies, 513 women; RR 0.64, 95% Confidence Interval (CI) 0.54 to 0.76). Methotrexate was associated with significantly more treatment failure than dactinomycin (five studies, 513 women; RR 3.81, 95% CI 1.64 to 8.86). We consider this evidence to be of a moderate quality.There was no significant difference between the two groups with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too heterogeneous to be conclusive. No severe adverse effects (SAEs) occurred in either group in three out of the five included studies and there was no significant difference in SAEs between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%), however, there was a trend towards fewer SAEs in the methotrexate group. We considered this evidence to be of a low quality due to substantial heterogeneity and low consistency in the occurrence/reporting of SAEs between trials. AUTHORS' CONCLUSIONS: Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard.We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings.