Lymph Node Metastases In Women Research Articles

Risk factors for lymph node metastasis in women with FIGO 2018 IA cervical cancer with a horizontal spread of > 7 mm

BackgroundIn the FIGO 2018 classification, women with cervical cancer and a depth of invasion ≤ 5 mm and a horizontal spread of > 7 mm in excisional biopsy with tumour-free margins, are now classified as stage IA instead of IB. This stage shift may reduce the likelihood of surgical lymph node staging. It is therefore crucial to estimate the risk and risk factors of lymph node metastasis (pN+) in this group. MethodsWomen diagnosed with cervical cancer between 2005 and 2022 were identified from nationwide population-based registries from the Netherlands, Denmark, and Sweden. Inclusion criteria were squamous cell carcinoma or adenocarcinoma, FIGO 2009 stage IB1, a depth of invasion ≤ 5 mm and horizontal spread of > 7–≤ 40 mm. All cases underwent radical hysterectomy or radical trachelectomy, and surgical lymph node staging. Logistic regression was used to identify risk factors of pN+. ResultsWe included 992 women (pN+ 4.1 %; n = 41). Lymphovascular space invasion (LVSI) was a significant risk factor of pN+ (odds ratio 4.26, 95 % confidence interval 2.24–8.32). Accordingly, the risk of pN+ was ≥ 7.3 % in LVSI-positive tumours. The risk was lowest in LVSI-negative tumours with a size of > 7–≤ 20 mm (2.2 %), although this varied by depth of invasion and histological subtype (pN+ range 0.6–5.1 %). ConclusionWomen with LVSI-positive FIGO 2018 IA cervical cancer and a horizontal spread > 7 mm, should undergo surgical lymph node staging. In LVSI-negative tumours, lymph node staging should not be routinely performed; tumour size, depth of invasion and histology should be considered.

Diffusion Weighted Imaging for the Assessment of Lymph Node Metastases in Women with Cervical Cancer: A Meta-analysis of the Apparent Diffusion Coefficient Values

PurposeTo assess the diagnostic performance of Diffusion Weighted Imaging (DWI) and provide optimal apparent diffusion coefficient (ADC) cut-off values for differentiating between benign and metastatic lymph nodes in women with uterine cervical cancer. MethodMEDLINE and EMBASE databases were searched. Methodological quality was assessed with QUADAS-2. Data-analysis was performed for three subgroups: 1. All studies; 2. Studies with maximum b-values of 800 s/mm², and 3. Studies containing b-values of 1000 s/mm². Receiver-operating characteristics (ROC) curves were constructed and the area under the curve (AUC) was calculated. The maximum Youden index was used to determine optimal ADC cut-off values, following calculations of sensitivity and specificity. ResultsSixteen articles (1156 patients) were included. Overall, their quality was limited. For all studies combined, the optimum ADC cut-off value was 0.985 x 10⁻³ mm²/s at maximum Youden Index of 0.77, resulting in sensitivity and specificity of 84%, and 94%, respectively. Studies with b-values up to 800 s/mm², gave an optimum ADC cut-off value of 0.985 x 10⁻³ mm²/s at maximum Youden Index of 0.62, with a sensitivity and specificity of 62%, and 100%. Studies containing b-values of 1000 s/mm² gave an optimum ADC cut-off value of 0.9435 x 10⁻³ mm²/s at maximum Youden Index of 0.93, with a sensitivity and specificity of 100%, and 93%, respectively. ConclusionsStudies using DWI including b-values of 1000 s/mm² have higher sensitivity and specificity than those with b-values up to 800 s/mm². At the cut-off value of 0.9435 x 10⁻³ mm²/s DWI can sufficiently discriminate between benign and metastatic lymph nodes.

A machine learning-based prediction model of pelvic lymph node metastasis in women with early-stage cervical cancer.

To develop a novel machine learning-based preoperative prediction model for pelvic lymph node metastasis (PLNM) in early-stage cervical cancer by combining the clinical findings and preoperative computerized tomography (CT) of the whole abdomen and pelvis. Patients diagnosed with International Federation of Gynecology and Obstetrics stage IA2-IIA1 squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the cervix who had primary radical surgery with bilateral pelvic lymphadenectomy from January 1, 2003 to December 31, 2020, were included. Seven supervised machine learning algorithms, including logistic regression, random forest, support vector machine, adaptive boosting, gradient boosting, extreme gradient boosting, and category boosting, were used to evaluate the risk of PLNM. PLNM was found in 199 (23.9%) of 832 patients included. Younger age, larger tumor size, higher stage, no prior conization, tumor appearance, adenosquamous histology, and vaginal metastasis as well as the CT findings of larger tumor size, parametrial metastasis, pelvic lymph node enlargement, and vaginal metastasis, were significantly associated with PLNM. The models' predictive performance, including accuracy (89.1%-90.6%), area under the receiver operating characteristics curve (86.9%-91.0%), sensitivity (77.4%-82.4%), specificity (92.1%-94.3%), positive predictive value (77.0%-81.7%), and negative predictive value (93.0%-94.4%), appeared satisfactory and comparable among all the algorithms. After optimizing the model's decision threshold to enhance the sensitivity to at least 95%, the 'highly sensitive' model was obtained with a 2.5%-4.4% false-negative rate of PLNM prediction. We developed prediction models for PLNM in early-stage cervical cancer with promising prediction performance in our setting. Further external validation in other populations is needed with potential clinical applications.

Trends in the pre-operative diagnosis and surgical management of axillary lymph node metastases in women with screen-detected breast cancer

AimThe aim of the current study was to investigate time-trends in pre-operative diagnosis and surgical treatment of axillary lymph node metastases in breast cancers detected at screening mammography. MethodsWe included all women who underwent screening mammography in the South of the Netherlands between 2005 and 2020. During a follow-up period of at least two years, data on clinical radiological examinations, biopsy procedures and surgical interventions were obtained. The 15 years of inclusion were divided into five cohorts of three years each. ResultsOf the 4049 women with invasive breast cancer, 22.1 % (896/4049) had axillary lymph node metastasis at pathology (ALN+). Percutaneous axillary biopsy was performed in 39.6 % (355/896) of these women, with the proportions of fine needle aspiration biopsy (FNAB) decreasing from 97.6 % (40/41) in 2005–2007 to 41.6 % (37/89) in 2017–2019 and core needle biopsy (CNB) rising from 2.4 % (1/41) in 2005–2007 to 58.4 % (52/89) in 2017–2019 (P < 0.001). Sensitivity of FNAB and CNB was comparable (77.4 % (188/243, 95%CI = 71%–82 %) versus 82.4 % (103/125), 95%CI = 74%–88 %) (P = 0.26). Pre-operative confirmation of ALN + by percutaneous biopsy ranged from 27.3 % (56/205) in 2011–2013 to 39.0 % (80/205) in 2017–2019, with no significant trend changes over time (P = 0.103). The proportion of ALN + women who underwent axillary lymph node dissection (ALND) decreased from 96.0 % (97/101) in 2005–2007 to 16.6 % (34/205) in 2017–2019 (P < 0.001). ConclusionPre-operative confirmation of axillary lymph node metastasis by ultrasound-guided biopsy did not rise despite the increased use of CNB at the expense of less invasive FNAB. A significant reduction in ALND was observed through the years.

Incidence and prognostic significance of inguinal lymph node metastasis in women with newly diagnosed epithelial ovarian cancer

Objective(s)To assess incidence and oncologic outcomes in women with advanced epithelial ovarian cancer (EOC) with inguinal lymph node metastasis (ILNM) at diagnosis. MethodsAn IRB-approved, retrospective single-institution cohort study was performed in women with stage III/IV EOC from 2009 to 2017. Patients with inguinal lymphadenopathy (defined as >1 cm in short axis) clinically or radiographically were identified. The impact of ILNM on progression-free survival (PFS) and overall survival (OS) were assessed. ResultsOf the 562 women with advanced EOC, 18 (3.2%) had ILNM at diagnosis, accounting for 25.7% of all patients with stage IVB disease (n = 70). Five patients (27.7%) had a known genetic predisposition for EOC, including BRCA1 (11.1%, n = 2), BRCA2 (11.1%, n = 2) and BRIP1 (5.6%, n = 1). The majority of patients underwent optimal primary cytoreductive surgery (CRS), including debulking of inguinal nodal metastasis (83.3%, n = 15), with 50% (n = 9) having no gross residual disease after surgery. There was no difference in PFS (19.9 vs. 19.9 vs. 17.2 months, p = 0.84) or OS (137.2 vs. 52.9 vs. 67.6 months, p = 0.29) in women with stage III/IV with ILNM, stage III/IV without ILNM, and stage IVB disease without ILNM, respectively. Progression-free survival was improved in women with ILNM who underwent an optimal resection to no macroscopic disease vs. non-optimal resection (27.4 vs. 14.3 months, p = 0.019). Median overall survival at the time of analysis did not reach statistical significance (137.2 vs. 57.3 months, p = 0.24). Conclusion(s)In this retrospective cohort study, 3.2% of women with advanced EOC presented with ILNM at diagnosis. Although ILNM did not portend worse clinical outcomes compared to all Stage III/IV and Stage IVB patients, respectively, resection to no gross residual disease was associated with improved PFS.

Factors Associated with Lymph Node Metastasis in Special Types of Invasive Breast Cancer at National Cancer Hospital in the Period of 2018 - 2021

This paper assesses the rate of lymph node metastasis and the correlation between lymph node metastasis and some pathological characteristics in special types of invasive breast cancer. In the paper, a descriptive cross‐sectional study was conducted on 200 patients with special types of invasive breast cancer at the Institute of Molecular Biology and Pathology - National Cancer Hospital from August 2020 to April 2021. The study results show that 32% of the 200 cases had nodal metastases. The factors associated with the increased risk of lymph node metastasis were of histological types (invasive lobular, invasive micropapillary carcinomas) (p = 0.000), high tumour grade (p = 0.000), the presence of lymphovascular invasion (p = 0.000), tumor-infiltrating lymphocytes (TILs) &lt; 10% (p = 0.000), the presence of tumor necrosis (p = 0.001), Her-2/neu overexpression (p = 0.01), Ki-67 ≥ 20% (p = 0.036), HER2-positive breast cancer (p = 0.015). Overall, the rate of lymph node metastasis was 32%. Histological type, tumour grade, the presence of lymphovascular invasion, TILs, tumor necrosis, Her-2/neu and Ki-67 expression, and molecular subtype were factors related to lymph node metastasis in special types of invasive breast cancer.&#x0D; Keywords:&#x0D; Lymph node metastasis, invasive breast cancer, special types.&#x0D; References&#x0D; [1] World Health Organization, Breast Tumors (5th ed), International Agency for Research on Cancer, Lyon, France, 2019.[2] K. M. Masters, S. L.Wong, R. C. Martin et al., Dermal Injection of Radioactive Colloid Is Superior to Peritumoral Injection for Breast Cancer Sentinel Lymph Node Biopsy: Results of A Multiinstitutional Study, Annals of Surgery, Vol. 233, No. 5, 2001, pp. 676, https://doi.org/10.1097/00000658-200105000-00012. [3] A. V. Ashturkar, G. S. Pathak, S. D. Deshmukh, H. T. 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Gelmon, Breast Carcinoma - Rare Types: Review of the Literature, Annals of Oncology, Vol. 20, No. 11, 2009, pp. 1763-1770, https://doi.org/10.1093/annonc/mdp245. [15] A. Caziuc, D. Schlanger, G. Amarinei, Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?, Vol. 8, No. 5, 2019, pp. 545, https://doi.org/10.3390/jcm8040545. [16] K. Takada, S. Kashiwagi, Y. Asano, Prediction of Lymph Node Metastasis by Tumor-Infiltrating Lymphocytes in T1 Breast Cancer, BMC Cancer, Vol. 20, No. 1, 2020, pp. 598, https://doi.org/10.1186/s12885-020-07101-y.[17] N. T. Ha, Evaluation of Axillary Lymph Node Status and Vascular Infiltration by Molecular Type of Breast Carcinoma, Master Thesis, Hanoi Medical University, Hanoi, 2018 (in Vietnamese).[18] J. 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Determining the axillary nodal status with four current imaging modalities including 18F-FDG PET/MRI in newly diagnosed breast cancer: A comparative study using histopathology as reference standard.

Purpose: To compare breast magnetic resonance imaging (MRI), thoracal MRI, thoracal 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/MRI and axillary sonography for the detection of axillary lymph node metastases in women with newly diagnosed breast cancer. Materials and Methods: This prospective double-center study included patients with newly diagnosed breast cancer between March 2018 and December 2019. Patients underwent thoracal (18F-FDG PET/)MRI, axillary sonography, and dedicated prone breast MRI. Datasets were evaluated separately regarding nodal status (nodal+ vs. nodal-). Histopathology served as reference standard in all patients. The diagnostic performance of breast MRI, thoracal MRI, thoracal PET/MRI and axillary sonography in detecting nodal positive patients was tested by creating receiver-operating-characteristic curves (ROC) with a calculated area under the curve (AUC). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all four modalities. A McNemar test was used to assess differences. Results: 112 female patients (mean age 53.04 ± 12.6 years) were evaluated. Thoracal PET/MRI showed the highest ROC-AUC with a value of 0.892. The AUC for breast MRI, thoracal MRI and sonography were 0.782, 0.814 and 0.834, respectively. Differences between thoracal PET/MRI and axillary sonography, thoracal MRI and breast MRI were statistically significant (PET/MRI vs. axillary sonography, P = 0.01; PET/MRI vs. thoracal MRI, P = 0.02; PET/MRI vs. breast MRI, P = 0.03). PET/MRI showed the highest sensitivity (81.8%, 36/44) (95%-CI: 67.29-91.81%) while axillary sonography had the highest specificity (98.5%, 65/66), 95%-CI: 91.84-99.96%). Conclusion: 18F-FDG PET/MRI outperforms axillary sonography, breast MRI and thoracal MRI in determining the axillary lymph node status. In a clinical setting, the combination of 18F-FDG PET/MRI and axillary sonography might be considered to provide even more accuracy in diagnosis.

Evaluation of Axillary Lymph Nodes in Breast Cancer Patients with Atopic Dermatitis

This study assessed the diagnostic accuracy of ultrasound in detecting axillary lymph node metastases in women with breast cancer and atopic dermatitis. We retrospectively reviewed the records of 91 breast cancer patients with a history of atopic dermatitis and compared the dimensions of the lymph nodes on ultrasonographic images of women with and without lymph node metastases diagnosed using histology. Using a major-axis length of ≥5 mm, a short-axis length of ≥5 mm and a cortical thickness of ≥2.3 mm as the criteria for diagnosing axillary lymph node metastases, the specificity was 12.7%, 41.3% and 58.7%, respectively. The low specificity of the ultrasound criteria makes ultrasound unsuitable for diagnosing axillary lymph nodes metastases in breast cancer patients with atopic dermatitis.

Semiquantitative evaluation of lymph-vascular space invasion in patients affected by endometrial cancer: Prognostic and clinical implications.

The interpretation of lymph-vascular space invasion (LVSI) is usually qualitative, as presence or absence. The aim of this study is to investigate the prognostic role of LVSI in patients affected by endometrial cancer, when evaluated with a semiquantitative analysis. This retrospective multicentre study enrolled patients who received a histologically confirmed diagnosis of endometrial cancer. The assessment of LVSI was semiquantitative in accordance with the three-tiered scoring system (absent, focaland diffuse). Among 1258 patients with surgical-stage endometrial cancer, LVSI has been found in 32.8% of cases (n=412), whose 12.7% (n=160) were focal, and 20% (n=252) diffuse. The rate of lymph node metastasis increased from the 5% in patients with no LVSI to 15% in patients with focal LVSI and 33% in those with diffuse LVSI (p<0.001). Distant recurrences were more frequent in patients with diffuse LVSI than in focal or no LVSI (24.9% versus 14.7% and 6.6%, respectively, p<0.001). Diffuse LVSI was found to significantly increase the risk of distant metastasis (adjusted odds ratio (A OR) 2.57, p<0.001). Adjuvant radiation were associated with improved overall survival (OS) and disease-free survival (DFS) in patients with diffuse LVSI. The presence of diffuse LVSI is an independent risk factor for both lymph node metastasis and distant recurrence in endometrial cancer patients, and it is associated with a significantly decreased OS and DFS. Adjuvant radiation improved survival regardless of grading, histotypeand lymph nodal metastasis in women with diffuse LVSI.

A modern assessment of the surgical pathologic spread of endometrial cancer

Objective: Since the publication of GOG 33 describing the surgical pathologic spread of endometrial cancer, staging criteria for endometrial cancer have evolved and there is a need for updated risk assessment of lymph node metastases in women with apparent early-stage tumors. The objective of this study was to examine the risk of nodal metastases in a contemporary group of women from across the United States based on pathologic risk factors including histology, depth of invasion, tumor grade, and lymphovascular space invasion (LVSI).

Ultrasound-based risk model for preoperative prediction of lymph-node metastases in women with endometrial cancer: model-development study.

To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68-0.78), the calibration slope was 1.06 (95% CI, 0.79-1.34) and the calibration intercept was 0.06 (95% CI, -0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Analysis of clinical characteristics of 854 patients with thyroid cancer

Objective:The aim of this study is to summarize and analyze the clinical features of thyroid cancer surgery patients, and provide information and guidance for clinical diagnosis and treatment. Method:The medical records of 854 patients with thyroid cancer who met the inclusion criteria from January 2013 to December 2018 were collected from the hospital's medical record system. Patients were grouped by age group and their stratified studies were performed on age, gender, pathological type, and cervical lymph node metastasis. Result:The total number of patients with thyroid cancer surgery in 2013-2018 showed an increasing trend. There was no significant difference in the age composition of thyroid cancer patients between different years （P>0.05）, but the age of 20-54 years old gradually increased with age, and reached a peak at 50-54 years old, then gradually decreased. There was no significant difference in gender composition between patients with thyroid cancer surgery in 2013-2018 （P>0.05）, but in 40-44 years old, the prevalence of women in the 50-54 age group was higher than that in men （P<0.05）, The prevalence of men in the 70-74 age group was higher than that in women （P<0.05）, and the peak period of both was 50-54 years old. Papillary carcinoma accounted for a high proportion （96.8%） in the pathological types of thyroid cancer surgery patients in 2013-2018, and the incidence of women in the 40-44 age group was higher than that in men（P<0.01）, in the 70-74 age range. The incidence was higher than that of women （P<0.01）. The incidence of follicular carcinoma （1%） was higher in men than in women （P<0.05）. The incidence of lymph node metastasis in women with thyroid cancer was lower than that in men （P<0.05）. Conclusion:The incidence of thyroid cancer in different age groups has its own characteristics, and prevention and control measures should be formulated according to age groups.

Risk factors for pelvic and para-aortic lymph node metastasis in endometrial cancer: A retrospective analysis of 284 patients

Aim: Hysterectomy is generally used to treat patients with endometrial cancer. Although lymphadenectomy can provide prognostic information, there are serious complications that can result from lymph node dissection. In order to avoid unnecessary surgical intervention, predictors related to both pelvic and para-aortic lymph node metastasis can be identified. In this study, we sought to define independent prognosticators for pelvic and para-aortic lymph node metastasis in women with endometrial cancer.Material and Methods: In total, 284 patients who were treated surgically between December 2009 and January 2019 were included in the study. The relationships between histopathological patient characteristics and definitive lymph node status were studied.Results: In multivariate analysis, lymphovascular space invasion (Adjusted Odds Ratio: 4.8, 95% Confidence Interval 2.4–17.5, p = 0.001) and deep myometrial invasion (Adjusted Odds Ratio 3.8, 95% Confidence Interval 1.1–14.3) were independent factors for pelvic lymph node metastasis. In multivariate analysis for para-aortic lymph node metastasis, lymphovascular space invasion (Adjusted Odds Ratio 5.9, 95% Confidence Interval 2.1–10.3) and pelvic lymph node metastasis (Adjusted Odds Ratio 20.8, 95% Confidence Interval 8.9–32.3) were independent prognostic factors significantly associated with the presence of para-aortic lymph node metastasis. Conclusion: The two independent histopathological factors identified for predicting the presence of pelvic lymph node metastasis were lymphovascular space invasion and outer half myometrial penetration of the tumor. Lymphovascular space invasion and pelvic lymph node metastasis were independently associated with the presence of para-aortic lymph node metastasis. Consideration of lymphadenectomy in patients who have evidence of outer half myometrial invasion or pelvic lymph node metastasis on preoperative imaging may be prudent. Lymphovascular space invasion and myometrial invasion findings on frozen section can be used before proceeding with lymphadenectomy in endometrial cancer.

Clinical and Ultrasound Characteristics of the Microcystic Elongated and Fragmented (MELF) Pattern in Endometrial Cancer According to the International Endometrial Tumor Analysis (IETA) criteria.

To describe sonographic features of the microcystic elongated and fragmented (MELF) pattern of myometrial invasion (MI) using the International Endometrial Tumor Analysis (IETA) criteria; to assess the effect of the MELF pattern on preoperative ultrasound evaluation of MI; and to determine the relationship of the MELF pattern to more advanced stage (≥ IB) and lymph node metastases in women with endometrioid endometrial cancer. We included 850 women with endometrioid endometrial cancer from the prospective IETA 4 study. Ultrasound experts performed all ultrasound examinations, according to the IETA protocol. Reference pathologists assessed the presence or absence of the MELF pattern. Sonographic features and accuracy of ultrasound assessment of MI were compared in cases with the presence and the absence of the MELF pattern. The MELF pattern was correlated to more advanced stage (≥IB) and lymph node metastases. The MELF pattern was present in 197 (23.2%) women. On preoperative ultrasound imaging the endometrium was thicker (p = 0.031), more richly vascularized (p = 0.003) with the multiple multifocal vessel pattern (p < 0.001) and the assessment of adenomyosis was more often uncertain (p < 0.001). The presence or the absence of the MELF pattern did not affect the accuracy of the assessment of MI. The MELF pattern was associated with deep myometrial invasion (≥ 50%) (p < 0.001), cervical stromal invasion (p = 0.037), more advanced stage (≥ IB) (p < 0.001) and lymph node metastases (p = 0.011). Tumors with the MELF pattern were slightly larger, more richly vascularized with multiple multifocal vessels and assessment of adenomyosis was more uncertain on ultrasound imaging. The MELF pattern did not increase the risk of underestimating MI in preoperative ultrasound staging. Tumors with the MELF pattern were more than twice as likely to have more advanced stage (≥ IB) and lymph node metastases.

Incidence of Lymph Node Metastases in Women With Low-Risk Early Cervical Cancer (

To determine the incidence of lymph node metastasis in women with low-risk cervical cancer stage IA2 or IB1 (<2 cm) without lymph-vascular space invasion. A multicenter retrospective study was performed in patients who underwent radical or simple hysterectomy, conization, or trachelectomy plus pelvic lymphadenectomy for cervical cancer between January 2000 and June 2016. A total of 271 patients were included in the study. Median age and body mass index were 46 years (range, 23-77 years) and 24 kg/m (range, 18-48 kg/m), respectively. Twenty-two patients had stage IA2 (8.1%), and 249 (91.9%) had stage IB1. The median tumor size was 14 mm (range, 5-20 mm). Tumor grades were 1 (n = 63 [23.2%]), 2 (n = 120 [44.3%]), 3 (n = 63 [23.2%]), and unknown (25 [9.2%]). Median depth stromal invasion was 6 mm (range, 3-20 mm). Histologic subtypes included squamous (n = 171 [63.1%]), adenocarcinoma (n = 92 [33.9%]), and adenosquamous (n = 8 [3.0%]). Overall incidence of lymph node metastasis was 2.9% (n = 8). The incidence of lymph node involvement in G1, G2, and G3 was 0% (0/63), 5% (6/120), and 3.1% (2/63), respectively. No patient with stage IA2 (regardless of grade or histology) or G1 cervical cancer less than 2 cm (stage IB1) had lymph node metastasis. Patients with stage IA2 or IB1 (G1) with tumor size of less than 2 cm and no lymph-vascular space invasion may not need lymph node evaluation. On the other hand, 95% and 98% of patients with grade 2 or 3 tumors, respectively, could potentially undergo an unnecessary lymphadenectomy. Further studies with bigger sample size are required to confirm these results.

Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer

Application of deep learning algorithms to whole-slide pathology images can potentially improve diagnostic accuracy and efficiency. Assess the performance of automated deep learning algorithms at detecting metastases in hematoxylin and eosin-stained tissue sections of lymph nodes of women with breast cancer and compare it with pathologists' diagnoses in a diagnostic setting. Researcher challenge competition (CAMELYON16) to develop automated solutions for detecting lymph node metastases (November 2015-November 2016). A training data set of whole-slide images from 2 centers in the Netherlands with (n = 110) and without (n = 160) nodal metastases verified by immunohistochemical staining were provided to challenge participants to build algorithms. Algorithm performance was evaluated in an independent test set of 129 whole-slide images (49 with and 80 without metastases). The same test set of corresponding glass slides was also evaluated by a panel of 11 pathologists with time constraint (WTC) from the Netherlands to ascertain likelihood of nodal metastases for each slide in a flexible 2-hour session, simulating routine pathology workflow, and by 1 pathologist without time constraint (WOTC). Deep learning algorithms submitted as part of a challenge competition or pathologist interpretation. The presence of specific metastatic foci and the absence vs presence of lymph node metastasis in a slide or image using receiver operating characteristic curve analysis. The 11 pathologists participating in the simulation exercise rated their diagnostic confidence as definitely normal, probably normal, equivocal, probably tumor, or definitely tumor. The area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.556 to 0.994. The top-performing algorithm achieved a lesion-level, true-positive fraction comparable with that of the pathologist WOTC (72.4% [95% CI, 64.3%-80.4%]) at a mean of 0.0125 false-positives per normal whole-slide image. For the whole-slide image classification task, the best algorithm (AUC, 0.994 [95% CI, 0.983-0.999]) performed significantly better than the pathologists WTC in a diagnostic simulation (mean AUC, 0.810 [range, 0.738-0.884]; P < .001). The top 5 algorithms had a mean AUC that was comparable with the pathologist interpreting the slides in the absence of time constraints (mean AUC, 0.960 [range, 0.923-0.994] for the top 5 algorithms vs 0.966 [95% CI, 0.927-0.998] for the pathologist WOTC). In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting.

Lymphadenectomy for the management of endometrial cancer.

This is an update of a previous Cochrane review published in Issue 1, 2010 and updated in Issue 9, 2015. The role of lymphadenectomy in surgical management of endometrial cancer remains controversial. Lymph node metastases can be found in approximately 10% of women who before surgery are thought to have cancer confined to the womb. Removal of all pelvic and para-aortic lymph nodes (lymphadenectomy) at initial surgery has been widely advocated, and pelvic and para-aortic lymphadenectomy remains part of the FIGO (International Federation of Gynaecology and Obstetrics) staging system for endometrial cancer. This recommendation is based on data from studies that suggested improvement in survival following pelvic and para-aortic lymphadenectomy. However, these studies were not randomised controlled trials (RCTs), and treatment of pelvic lymph nodes may not confer a direct therapeutic benefit, other than allocating women to poorer prognosis groups. Furthermore, the Cochrane review and meta-analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early-stage endometrial cancer found no survival advantage. Surgical removal of pelvic and para-aortic lymph nodes has serious potential short-term and long-term sequelae. Therefore, it is important to investigate the clinical value of this treatment. To evaluate the effectiveness and safety of lymphadenectomy for the management of endometrial cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to June 2009 for the original review, updated the search to June 2015 for the last updated version and further extended the search to March 2017 for this version of the review. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field. RCTs and quasi-RCTs that compared lymphadenectomy versus no lymphadenectomy in adult women diagnosed with endometrial cancer. Two review authors independently extracted data and assessed risk of bias. Hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received lymphadenectomy versus those with no lymphadenectomy were pooled in random-effects meta-analyses. We assessed the quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. 978 unique references were identified via the search strategy. All but 50 were excluded by title and abstract screening. Three RCTs met the inclusion criteria; for one small RCT, data were insufficient for inclusion in the meta-analysis. The two RCTs included in the analysis randomly assigned 1945 women, reported HRs for survival adjusted for prognostic factors and based on 1851 women and had an overall low risk of bias, as they satisfied four of the assessment criteria. The third study had an overall unclear risk of bias, as information provided was not adequate concerning random sequence generation, allocation concealment, blinding, or completeness of outcome reporting.Results of the meta-analysis remained unchanged from the previous versions of this review and indicated no differences in overall and recurrence-free survival between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy (pooled hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.81 to 1.43; HR 1.23, 95% CI 0.96 to 1.58 for overall and recurrence-free survival, respectively) (1851 participants, two studies; moderate-quality evidence).We found no difference in risk of direct surgical morbidity between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy. However, women who underwent lymphadenectomy had a significantly higher risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation than those who did not undergo lymphadenectomy (RR 3.72, 95% CI 1.04 to 13.27; RR 8.39, 95% CI 4.06 to 17.33 for risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation, respectively) (1922 participants, two studies; high-quality evidence). This review found no evidence that lymphadenectomy decreases risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. Evidence on serious adverse events suggests that women who undergo lymphadenectomy are more likely to experience surgery-related systemic morbidity or lymphoedema/lymphocyst formation. Currently, no RCT evidence shows the impact of lymphadenectomy in women with higher-stage disease and in those at high risk of disease recurrence.

Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not.

CA 125 and Grade 1 Endometrial Cancer

INTRODUCTION: The purpose of this article was to relate pre-operative serum CA 125 to risk of nodal metastases in women with grade 1 endometrial cancer that were fully surgically staged. METHODS: Charts were reviewed to determine all patients with pre-operative grade 1 endometrial carcinoma and a serum CA 125 undergoing complete surgical staging. Charts were also reviewed for final stage, grade, and site of metastases. All serum CA 125s were drawn within 3 weeks of definitive surgery. RESULTS: Analysis was completed on 737 patients with grade 1 endometrial cancer. The mean age of the population was 61.9 years (95% CI 61.3–62.4). Extra uterine disease was found in 14.7% of patients and nodal disease in 12.6%. A significant difference in BMI was seen between those not having lymph node metastases (mean 38.7 kg/m2; 95% CI 38.1–39.3) and those having positive nodes (mean 35.3 kg/m2; 95% CI 34.3–36.3) (P<.001). The mean CA 125 for the cohort was 25.6 mIU/mL (95% CI 22.0–29.2). No patients with pre-operative grade 1 disease and a CA 125 <15 mIU/mL (0/239) had nodal disease at surgical staging while 18.7% (93/498) with a CA 125 >15 mIU/mL had nodal metastases (P<.001). CONCLUSION: In patients with grade 1 endometrial adenocarcinomas, CA 125 can be used to determine who needs full surgical staging with minimal risk of missing nodal positive patients.

Magnitude of risk for nodal metastasis associated with lymphvascular space invasion for endometrial cancer

ObjectivesWhile lymphvascular space invasion (LVSI) is a risk factor for nodal metastasis in endometrial cancer, the magnitude of risk is poorly described. We examined the risk of nodal metastasis associated with LVSI for various combinations of tumor grade and depth of invasion and examined the effect of LVSI on survival. MethodsWe identified patients with T1A (<50% myoinvasion) and T1B (>50% myoinvasion) endometrioid adenocarcinomas of the endometrium diagnosed between 2010 and 2012 and recorded in the National Cancer Database. The risk of nodal metastasis associated with LVSI stratified by grade and stage is reported. The association of LVSI and survival was examined using Kaplan–Meier analyses and Cox proportional hazards models. ResultsWe identified 25,907 patients, including 3928 (15.2%) with LVSI. Among patients with LVSI, 21.0% had positive lymph nodes, compared to 2.1% in patients without LVSI (P<0.0001). In analyses stratified by stage and grade, LVSI was associated with increased risks of LN metastasis by a magnitude of 3 to over 10-fold. In a multivariable model controlling for clinical and demographic characteristics, the risk ratio of nodal disease with LVSI was 9.29 (95% CI, 7.29–11.84) for T1A tumors and 4.64 (95% CI 3.99–5.39) for T1B tumors. LVSI was associated with decreased survival even after adjustment for the presence of lymph node metastases (HR=1.92, 95% CI 1.56–2.36). ConclusionsLVSI is independently associated with lymph node metastases in women with apparent early-stage endometrial cancer and an independent predictor of survival even after adjustment for the presence of lymph node metastases.