In this prospective randomized trial, minimally invasive radical hysterectomy resulted in lower rates of disease-free survival and overall survival than open abdominal radical hysterectomy among ...women with early-stage cervical cancer.
A prospective randomized trial and an epidemiologic study that used large cancer databases (National Cancer Database and SEER) both showed that minimally invasive radical hysterectomy was associated with shorter survival in early cervical cancer than open abdominal radical hysterectomy.
Cancer is a leading public health issue globally, and diagnosis is often associated with poor outcomes and reduced patient survival. One of the major contributors to the fatality resultant of cancer ...is the development of resistance to chemotherapy, known as chemoresistance. Furthermore, there are limitations in our ability to identify patients that will respond to therapy, versus patients that will develop relapse, and display limited or no response to treatment. This often leads to patients being subjected to multiple futile treatment cycles, and results in a reduction in their quality of life. Therefore, there is an urgent clinical need to develop tools to identify patients at risk of chemoresistance, and recent literature has suggested that small extracellular vesicles, known as exosomes, may be a vital source of information. Extracellular vesicles (EV) are membrane bound vesicles, involved in cell-cell communication, through the transfer of their cargo, which includes proteins, lipids, and miRNAs. A defined exploration strategy was performed in this systematic review in order to provide a compilation of key EV miRNAs which may be predictive of chemoresistance. We searched the PubMed, Science Direct, and Scopus databases using the following keywords: Extracellular vesicles OR exosomes OR EVs AND miRNA AND Chemotherapy OR Chemoresistance OR Cancer Recurrence from 2010 to 2020. We found 31 articles that reported key EV-associated miRNAs involved in cancer recurrence related to chemoresistance. Interestingly, multiple studies of the same tumor type identified different microRNAs, and few studies identified the same ones. Specifically, miR-21, miR-222, and miR-155 displayed roles in response to chemotherapy, and were found to be common in colorectal cancer, ovarian cancer, breast cancer, and diffuse large B cell lymphoma patients (DLBCL). miR-21 and miR-222 were found to favour the development of chemoresistance, whereas miR-155 exhibited a contrasting role, depending on the type of primary tumor. Whilst high levels of miR-155 were found to correlate with chemotherapy resistance in DLBCL, it was found to be predictive of an effective response towards chemotherapy in breast cancer. Thus, further research regarding the roles of these miRNAs would be beneficial in terms of designing novel tools to counteract the progression of cancer in a not-to-distant future.
Abstract Objective Cancer-related lymphedema is a debilitating condition that adversely influences function, health and quality of life. The purpose of this study was to assess the prevalence, ...incidence, and risk factors of lower-limb lymphedema pre- through to 24 months post-surgery for gynecological cancer. Methods A clinic-based sample of women (n = 408) with gynecological cancer participated in a prospective, longitudinal study (2008–2011) using self-reported measures (swelling in one or both legs) and objectively measured lymphedema (bioimpedance spectroscopy) at baseline (pre-surgery), six weeks–three months, 6–12 months, and 15–24 months post-surgery. Results At pre-surgery, 15% of women self-reported lymphedema and 27% had measurable evidence of lymphedema. By 24 months post-surgery, incidence of new self-reported or measured lymphedema was 45% and 37%, respectively. Three-quarters of these new cases presented by 12-months post-treatment. While lymphedema was transient for some women, 60% had persistent lymphedema. More extensive lymph node dissection, receipt of chemotherapy and radiation therapy, increasing body mass index, insufficient levels of physical activity, diagnosis of vulvar/vaginal cancer and presence of pre-treatment lymphedema were identified as potential risk factors (p < 0.05). Conclusion Findings support the need for integration of pre-surgical assessment, and prospective, post-treatment surveillance of lymphedema into gynecological cancer care. Future research exploring the role of maintaining healthy body weight, regular physical activity and education about early detection of lymphedema to improve gynecological cancer survivorship is warranted.
Introduction
There has been a constant increase in the number of published surgical videos with preference for open-access sources, but the proportion of videos undergoing peer-review prior to ...publication has markedly decreased, raising questions over quality of the educational content presented. The aim of this study was the development and validation of a standard framework for the appraisal of surgical videos submitted for presentation and publication, the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool.
Methods
An international committee identified items for inclusion in the LAP-VEGaS video assessment tool and finalised the marking score utilising Delphi methodology. The tool was finally validated by anonymous evaluation of selected videos by a group of validators not involved in the tool development.
Results
9 items were included in the LAP-VEGaS video assessment tool, with every item scoring from 0 (item not presented in the video) to 2 (item extensively presented in the video), with a total marking score ranging from 0 to 18. The LAP-VEGaS video assessment tool resulted highly accurate in identifying and selecting videos for acceptance for conference presentation and publication, with high level of internal consistency and generalisability.
Conclusions
We propose that peer review in adherence to the LAP-VEGaS video assessment tool could enhance the overall quality of published video outputs.
Graphic Abstract
•SLND has potentially favourable patient-centred outcomes over systematic LND.•High-quality evidence comparing SLND with other methods of staging is lacking.•SLND was associated with shorter ...operating times and lower estimated blood loss.•Intraoperative and postoperative complications were not conclusively different.
Sentinel lymph node dissection (SLND) is presently used by the majority of gynaecologic oncologists for surgical staging of endometrial cancer. SLND assimilated into routine surgical practice because it increases precision of surgical staging and may reduce morbidity compared to a full, systematic LND. Previous research focussed on the accuracy of SLND. Patient centred outcomes have never been conclusively demonstrated. The objective of this systematic review was to evaluate patient centred outcomes of SLND for endometrial cancer patients. Literature published in the last five years (January 2015 to April 2020) was retrieved from PubMed, EMBASE, and Cochrane library, across five domains: (1) perioperative outcomes; (2) adjuvant treatment; (3) patient-reported outcomes (PROs); (4) lymphedema, and (5) cost. Covidence software ascertained a standardised and monitored review process. We identified 21 eligible studies. Included studies were highly heterogeneous, with widely varying outcome measures and reporting. SLND was associated with shorter operating times and lower estimated blood loss compared to systematic LND, but intra-operative and post-operative complications were not conclusively different. There was either no impact, or a trend towards less adjuvant treatment used in patients with SLND compared to systematic LND. SLND had lower prevalence rates of lymphedema compared to systematic LND, although this was shown only in three retrospective studies. Costs of surgical staging were lowest for no node sampling, followed by SLND, then LND. PROs were unable to be compared because of a lack of studies. The quality of evidence on patient-centred outcomes associated with SLND for surgical staging of endometrial cancer is poor, particularly in PROs, lymphedema and cost. The available studies were vulnerable to bias and confounding.
Registration of Systematic Review: PROSPERO (CRD42020180339)
Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with ...germline mismatch repair (MMR) gene mutations.
Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS).
Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered.
Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.
Summary Background This two-stage randomised controlled trial, comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) for stage I endometrial cancer (LACE), began in ...2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved quality of life (QoL) up to 6 months after surgery compared with TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4·5 years is equivalent for TLH and TAH. Here, we present the results of stage 1. Methods Between Oct 7, 2005, and April 16, 2008, 361 participants were enrolled in the QoL substudy at 19 centres across Australia, New Zealand, and Hong Kong; 332 completed the QoL analysis. Randomisation was done centrally and independently from other study procedures via a computer-generated, web-based system (providing concealment of the next assigned treatment), using stratified permuted blocks of three and six patients. Patients with histologically confirmed stage I endometrioid adenocarcinoma and Eastern Cooperative Oncology Group performance status less than 2 were randomly assigned to TLH (n=190) or TAH (n=142), stratified by histological grade and study centre. Patients and study personnel were not masked to treatment assignment. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery, using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between groups in QoL change from baseline at early and late timepoints (a 5% difference was considered clinically significant). Analysis was done according to the intention-to-treat principle. Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. The LACE trial is registered with ClinicalTrials.gov , number NCT00096408. Findings Eight of 332 patients (2·4%) had treatment conversion—seven from TLH to TAH and one from TAH to TLH (patient preference). In the early phase of recovery, patients who had TLH reported significantly greater improvement in QoL from baseline compared with those who had TAH, in all subscales apart from emotional and social wellbeing. Improvements in QoL up to 6 months after surgery continued to favour TLH, except in the emotional and social wellbeing measures of FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Operating time was significantly longer in the TLH group (138 min SD 43) than in the TAH group (109 min 34; p=0·001). Although the proportion of intraoperative adverse events was similar between groups (TAH eight of 142 5·6% vs TLH 14 of 190 7·4%; p=0·53); postoperatively, twice as many patients in the TAH group experienced adverse events of grade 3 or higher (33 of 142 23·2% vs 22 of 190 11·6% in the TLH group; p=0·004). Postoperative serious adverse events occurred more in the TAH group (27 of 142 19·0%) than in the TLH group (16 of 190 7·9%; p=0·002). Interpretation QoL improvements from baseline during early and later phases of recovery, and the adverse event profile, favour TLH compared with TAH for treatment of stage I endometrial cancer. Funding Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council Western Australia; NHMRC project grant 456110 ; Cancer Australia project grant 631523 ; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.
Abstract Objectives Few studies have assessed the risk and impact of lymphedema among women treated for endometrial cancer. We aimed to quantify cumulative incidence of, and risk factors for ...developing lymphedema following treatment for endometrial cancer and estimate absolute risk for individuals. Further, we report unmet needs for help with lymphedema-specific issues. Methods Women treated for endometrial cancer (n = 1243) were followed-up 3–5 years after diagnosis; a subset of 643 completed a follow-up survey that asked about lymphedema and lymphedema-related support needs. We identified a diagnosis of secondary lymphedema from medical records or self-report. Multivariable logistic regression was used to evaluate risk factors and estimates. Results Overall, 13% of women developed lymphedema. Risk varied markedly with the number of lymph nodes removed and, to a lesser extent, receipt of adjuvant radiation or chemotherapy treatment, and use of nonsteroidal anti-inflammatory drugs (pre-diagnosis). The absolute risk of developing lymphedema was > 50% for women with 15 + nodes removed and 2–3 additional risk factors, 30–41% for those with 15 + nodes removed plus 0–1 risk factors or 6–14 nodes removed plus 3 risk factors, but ≤ 8% for women with no nodes removed or 1–5 nodes but no additional risk factors. Over half (55%) of those who developed lymphedema reported unmet need(s), particularly with lymphedema-related costs and pain. Conclusion Lymphedema is common; experienced by one in eight women following endometrial cancer. Women who have undergone lymphadenectomy have very high risks of lymphedema and should be informed how to self-monitor for symptoms. Affected women need greater levels of support.
Cancer survivors are at risk of developing a second primary cancer (SPC) later in life because of persisting effects of genetic and behavioural risk factors, the long-term sequelae of chemotherapy, ...radiotherapy and the passage of time. This is the first study with Austrian data on an array of entities, estimating the risk of SPCs in a population-based study by calculating standardized incidence ratios (SIRs).
This retrospective cohort study included all invasive incident cancer cases diagnosed within the years 1988 to 2005 being registered in the Tyrol and Vorarlberg Cancer Registries. Person years at risk (PYAR) were calculated from time of first diagnosis plus 2 months until the exit date, defined as the date of diagnosis of the SPC, date of death, or end of 2010, whichever came first. SIR for specific SPCs was calculated based on the risk of these patients for this specific cancer.
A total of 59,638 patients were diagnosed with cancer between 1988 and 2005 and 4949 SPCs were observed in 399,535 person-years of follow-up (median 5.7 years). Overall, neither males (SIR 0.90; 95% CI 0.86-0.93) nor females (SIR 1.00; 95% CI 0.96-1.05) had a significantly increased SIR of developing a SPC. The SIR for SPC decreased with age showing a SIR of 1.24 (95% CI 1.12-1.35) in the age group of 15-49 and a SIR of 0.85 (95% CI 0.82-0.89) in the age group of ≥ 65. If the site of the first primary cancer was head/neck/larynx cancer in males and females (SIR 1.88, 95% CI 1.67-2.11 and 1.74, 95% CI 1.30-2.28), cervix cancer in females (SIR 1.40, 95% CI 1.14-1.70), bladder cancer in males (SIR 1.20, 95% CI 1.07-1.34), kidney cancer in males and females (SIR 1.22, 95% 1.04-1.42 and 1.29, 95% CI 1.03-1.59), thyroid gland cancer in females (SIR 1.40, 95% CI 1.11-1.75), patients showed elevated SIR, developing a SPC.
Survivors of head & neck, bladder/kidney, thyroid cancer and younger patients show elevated SIRs, developing a SPC. This has possible implications for surveillance strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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