Abstract Objective Recent reviews on the sentinel lymph node (SLN) procedure in cervical cancer have shown that bilateral SLN detection and ultra staging are safe and superior options compared to a ...unilateral detection, frozen section and H&E analysis. So far, nobody identified a subgroup of patients in whom a SLN procedure may replace pelvic lymph node dissection (PLND). Methods We searched PubMed, Embase, CINAHL and Cochrane from inception up to November 26, 2014. Studies reporting SLN detection, and/or histological outcome of the SLN were included. Methodological quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool by two independent reviewers. Data to complete 2 × 2 contingency tables were obtained, and patient-, study- and technique characteristics were extracted. Results were pooled and plotted in forest plots. Results Forty-seven studies (4130 patients) were analyzed. Pooled data of diagnostic accuracy on ultra staging (18 studies; 1275 patients) showed a sensitivity of 94% (95% CI 80–99%) and negative predictive values ranging between 91 and 100%. After ultra staging, 19 false negative results remained. Prerequisites such as early FIGO stage (IA2, IB1, IIA primary tumor size < 40 mm), no suspicious pre-, and per-operative lymph nodes, and bilateral negative SLNs after ultra staging resulted in 1 remaining false negative result among 1257 patients (0.08%). Pooled data on a combined tracer in early stage cervical cancer patients with primary tumor size < 20 mm (6 studies; 276 patients) resulted in 87% bilateral SLN detection. Conclusions Early stage cervical cancer patients (FIGO IA2, IB1, IIA primary tumor size < 40 mm) who have no suspicious pre-, and per-operative lymph nodes, and have bilateral negative SLNs after ultra staging, have a residual risk of 0.08% (1/1257) on occult metastases. On the basis of these results we recommend not to perform a full PLND in these patients.
Recently, the safety of laparoscopic radical hysterectomy (LRH) has been called into question in early-stage cervical cancer. This study aimed to evaluate overall survival (OS) and disease-free ...survival (DFS) in patients treated with abdominal radical hysterectomy (ARH) and LRH for early-stage cervical cancer and to provide a literature review.
Patients diagnosed between 2010 and 2017 with International Federation of Gynaecology and Obstetrics (2009) stage IA2 with lymphovascular space invasion, IB1 and IIA1, were identified from the Netherlands Cancer Registry. Cox regression with propensity score, based on inverse probability treatment weighting, was applied to examine the effect of surgical approach on 5-year survival and calculate hazard ratios (HR) and 95% confidence intervals (CIs). Literature review included observational studies with (i) analysis on tumours ≤4 cm (ii) median follow-up ≥30 months (iii) ≥5 events per predictor parameter in multivariable analysis or a propensity score.
Of the 1109 patients, LRH was performed in 33%. Higher mortality (9.4% vs. 4.6%) and recurrence (13.1% vs. 7.3%) were observed in ARH than LRH. However, adjusted analyses showed similar DFS (89.4% vs. 90.2%), HR 0.92 95% CI: 0.52–1.60) and OS (95.2% vs. 95.5%), HR 0.94 95% CI: 0.43–2.04). Analyses on tumour size (<2/≥2 cm) also gave similar survival rates. Review of nine studies showed no distinct advantage of ARH, especially in tumours <2 cm.
After adjustment, our retrospective study showed equal oncological outcomes between ARH and LRH for early-stage cervical cancer – also in tumours <2 cm. This is in correspondence with results from our literature review.
•Oncological outcome is equal after abdominal and laparoscopic radical hysterectomy.•Disease-free survival and overall survival are equal in tumours <2 cm.•The exact role of laparoscopy should be examined in prospective randomised trials.
The aims of this study were to evaluate the safety and impact of pretreatment surgical para-aortic lymph node staging (PALNS) in advanced cervical cancer (International Federation of Gynecology and ...Obstetrics stage IB2-IVA) and to evaluate the preoperative imaging of PALNs.
We searched in PubMed and the Cochrane Library to identify data investigating the role of surgical PALNS. Selection criteria included English-language and advanced-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IB2-IVA) articles.
Twenty-two articles were included. Para-aortic lymph node metastases were present in 18% (range, 8%-42%) of all patients with cervical cancer stage IB to IVA. The proportions of positive para-aortic nodes on histological analysis with suspicious para-aortic nodes on imaging (positive predictive value) were 20% to 66%, 0% to 27%, 86% to 100%, and 50% to 75% for computed tomographic (CT) scan, magnetic resonance imaging (MRI) scan, positron emission tomography (PET), and PET-CT, respectively. The negative predictive values of the imaging techniques were 53% to 92% for CT scan, 75% to 91% for MRI, 87% to 94% for PET, and 83% to 92% for PET-CT. The proportions of histologically proven PALN metastasis with normal findings on imaging were 9% to 35% for CT scan and MRI, 4% to 11% for PET, and 6% to 15% for PET-CT. The mean complication rate of PALNS is 9%, with a range of 4% to 24%, with lymphocysts being the most common complication.
Pretreatment surgical PALN dissection or sampling is feasible, with low complication rates and short delay in starting treatment. Pretreatment PET or PET-CT is the most accurate imaging method in detecting PALN metastases but has limitations detecting microscopic tumor volumes. Even with normal findings on PET-CT, PALN metastases are present in 4% to 15% of patients. Positive PALNs in stage IB2 to IVA cervical cancer will lead to modification of treatment and may lead to better overall and disease-free survival.
Data on health-related quality of life (HRQoL) is paramount for shared and evidence based decision-making. Since an overview of cervical cancer HRQoL tools and their validity appears to be lacking, ...we performed a systematic review on usage of disease specific HRQoL instruments in cervical cancer patients and their psychometric properties to identify the most suitable cervical cancer specific HRQoL tool.
We searched Pubmed, EMBASE and PsycINFO from inception up to 18 October 2016 for studies on quality of life in cervical cancer patients. Data extraction and HRQoL identification was performed by two independent reviewers. Validation studies of the identified cervical cancer specific HRQoL tools were retrieved and assessed on psychometric properties using the COSMIN checklist. All used cervical cancer specific HRQoL instruments were scored and ranked according to their psychometric properties.
We included 156 studies (20,690 patients) and identified 31 HRQoL tools. The EORTC QLQ-CX24 (35 studies; 5,556 patients) and FACT-Cx (22 studies; 4,224 patients) were the only cervical cancer specific tools. The EORTC QLQ-CX24 had 4 out of 9 positive rated psychometric properties; internal consistency, content and construct validity, and agreement. Criterion validity, reliability, and interpretability scored doubtful. Responsiveness and floor- and ceiling effects were not reported. The FACT-Cx had 2 out of 9 positive rated psychometric properties; internal consistency and agreement. Content validity, reliability, and interpretability scored doubtful while criterion and construct validity scored negative. Responsiveness and floor- and ceiling effects were not reported.
The validity of the often used EORTC QLQ-CX24 questionnaire for cervical cancer patients remains uncertain as 5 out of 9 psychometric properties were doubtful or not reported in current literature. Cervical cancer specific HRQoL tools should therefore always be used in conjunction with validated generic cancer HRQoL tools until proper validity has been proven, or a more valid tool has been developed.
Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer (ECC); however, certain risk factors may necessitate additional treatments and impact fertility. ...This review examines the prevalence of these risk factors and available treatment options.
A systematic search was conducted of studies including patients with ECC (IA1 with LVSI, IA2, IB1 (FIGO 2009)) who underwent FSS.
Sixty-four articles, comprising a total of 4118 women planned for FSS, were included. High- or intermediate-risk histologic features were found in 638 (15.5%) women: 5.1% had positive lymph node(s), 4.1% had positive resection margins, 0.3% had parametrial involvement, 1.0% had unspecified high-risk features, and 5.1% had intermediate-risk histology (primarily based on the Sedlis criteria). Adjuvant treatment impaired fertility in all women with adjuvant hysterectomy and/or (chemo)radiation (58.7%). Adjuvant chemotherapy was given to 1351 (32.8%) patients, which may reduce fertility.
Fertility preservation could be achieved in most women; but high- or intermediate-risk factors necessitate more extensive surgery or radiotherapy leading to infertility. Adjuvant chemotherapy could be an alternative treatment option considering its effectiveness, safety and higher change in fertility preservation. The low incidence of parametrial involvement justifies waiving parametrectomy in tumors < 2 cm.
Lipid metabolism is altered in several cancer settings leading to different ratios of intermediates. Ovarian cancer is the most lethal gynecological malignancy. Cancer cells disperse in the abdominal ...space and ascites occurs. T cells obtained from ascites are unable to proliferate after an antigenic stimulus. The proliferation of ascites-derived T cells can be restored after culturing the cells for ten days in normal culture medium. No pathway aberrancies were detected. The acellular fraction of ascites can inhibit the proliferation of autologous as well as allogeneic peripheral blood lymphocytes, indicating the presence of soluble factors that interfere with T cell functionality. Therefore, we analyzed 109 lipid mediators and found differentially regulated lipids in suppressive ascitic fluid compared to normal abdominal fluid. Our study indicates the presence of lipid intermediates in ascites of ovarian cancer patients, which coincidences with T cell dysfunctionality. Since the immune system in the abdominal cavity is compromised, this may explain the high seeding efficiency of disseminated tumor cells. Further research is needed to fully understand the correlation between the various lipids and T cell proliferation, which could lead to new treatment options.
Abstract Epithelial ovarian cancer (EOC) is an immunogenic tumour and exploits many suppressive ways to escape immune eradication. EOC is known to spread primarily by tumour cell implantations in ...peritoneal cavity. Therefore, ascites may be an ideal fluid compartment to unravel the immune status of the peritoneal cavity. We analysed the expression of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TNF-β, TGF-β and CCL22 in ovarian cancer ascites, representing immune activating and suppressing cytokines. We observed high expression of pro-inflammatory cytokines IL-6, IL-8 and immune suppressive cytokines IL-10, CCL22 and TGF-β in most samples whereas Th1 (IL-12p70, IFN-γ) and Th2 (IL-4, IL-5) cytokines were only detectable in 13% of the samples. TGF-β was only detected in latent form, questioning its immune suppressive role. CCL22 was in similar levels present in early stage compared to advanced stage tumours. At advanced stage, we observed a negative correlation with CCL22 levels and Th1/2 cytokine expression. We found a positive correlation between IL-6 concentration in ascites and residual disease after debulking. Additionally, IL-6 levels were remarkably higher at recurrence compared to primary advanced disease, which opens an opportunity for inhibition of IL-6 expression in the prevention of recurrence. Despite the heterogeneity of EOC and the complexity of cytokine functions, our results show that cytokine analysis in ascites may aid in understanding tumour–host interaction in EOC.
The aim was to investigate the incidence of sentinel lymph node (SLN) metastases and the contribution of SLN mapping in presumed low- and intermediate-risk endometrial cancer (EC). A multicenter, ...prospective cohort study in presumed low- and intermediate-risk EC patients was performed. Patients underwent SLN mapping using cervical injections of indocyanine green and a minimally invasive hysterectomy with bilateral salpingo-oophorectomy. The primary outcome was the incidence of SLN metastases, leading to adjusted adjuvant treatment. Secondary outcomes were the SLN detection rate and the occurrence of complications. Descriptive statistics and univariate general linear model analyses were used. A total of 152 patients were enrolled, with overall and bilateral SLN detection rates of 91% and 61%, respectively. At final histology, 78.9% of patients (
= 120) had truly low- and intermediate-risk EC. Macro- and micro-metastases were present in 11.2% (
= 17/152), and three patients had isolated tumor cells (2.0%). Nine patients (5.9%) had addition of adjuvant radiotherapy based on SLN metastases only. In 2.0% of patients with high-risk disease, adjuvant therapy was more limited due to negative SLNs. This study emphasizes the importance of SLN mapping in presumed early-stage, grade 1 and 2 EC, leading to individualized adjuvant management, resulting in less undertreatment and overtreatment.
Sentinel lymph node mapping has emerged as an alternative to lymphadenectomy in evaluating the lymph node status in endometrial cancer. Several pathological methods to examine the sentinel lymph node ...are applied internationally. The aim of this study was to determine the value of ultrastaging and to assess the ultrastaging method with the highest detection rate of metastases.
A systematic review was conducted. Inclusion criteria were: pathologically-confirmed endometrial cancer with sentinel lymph node mapping, report of the histological outcomes, metastases found by hematoxylin and eosin staining and metastases found by ultrastaging were separately mentioned, and description of the ultrastaging method. The primary outcome was the detection of metastases found by ultrastaging that were not detected by routine hematoxylin and eosin staining. The secondary outcome was the difference in detection rate of metastases between several ultrastaging methods. Random effects meta-analyses were conducted.
Fifteen studies were selected, including 2259 patients. Sentinel lymph nodes were examined by routine hematoxylin and eosin staining. Subsequently, multiple ultrastaging methods were used, with differences in macroscopic slicing (bread-loaf/longitudinal), number of microscopic slides, and distance between slides, but all used immunohistochemistry. A positive sentinel lymph node was found in 14% of patients. In 37% of these, this was detected only by ultrastaging. Using more ultrastaging slides did not result in a higher detection rate. Bread-loaf slicing led to a higher detection rate compared with longitudinal slicing (mean detection rates 53% and 33%, respectively).
Pathological ultrastaging after routine hematoxylin and eosin staining in endometrial cancer patients has led to an increased detection rate of sentinel lymph node metastases. Different ultrastaging methods are used, with a preference for bread-loaf slicing. However, due to the large heterogeneity of the studies, assessing which ultrastaging method has the highest detection rate of sentinel lymph node metastases was not possible.
To evaluate consecutive vaginal radical trachelectomies (VRTs) in early-stage cervical cancer in the 2 main referral centers for fertility-preserving surgery in the Netherlands.
Oncology, fertility, ...and obstetrical data were recorded in a regional database of all VRTs without neoadjuvant chemotherapy performed in 2 major referral centers between 2000 and 2015.
Most of the patients (91.7%) had stage IB1 disease. In 72.0%, squamous cell carcinoma was the histologic diagnosis; in 24.2%, adenocarcinoma; and in 3.8%, adenosquamous carcinoma. The median follow-up was 51 months.Nine (6.8%) recurrences occurred, 4 resulting in death of disease (death rate, 3.0%). Recurrence rates were 12.5% for adenocarcinoma, 20% for adenosquamous carcinoma, and 4.2% for squamous cell carcinoma (P < 0.01).From 117 women, data about fertility and obstetrical outcome were obtained. Almost 60% of women attempted to conceive after a VRT. Of these women, 40% needed fertility treatment. A total of 47 pregnancies were established, and a total of 37 children were born of which 30 (81.1%) were delivered after 32 weeks of gestational age.
Nonsquamous cell histology and high-grade disease are associated with a significantly higher risk of recurrence in the univariate and multivariate analyses. Women with both these histology features should be counseled reticently for VRT.Pregnancies after VRT must be regarded as high-risk pregnancies with a high prematurity rate.
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