Lymphovascular Space Involvement Research Articles

Comparison of outcomes between early-stage cervical cancer patients without high-risk factors undergoing adjuvant concurrent chemoradiotherapy and radiotherapy alone after radical surgery.

For patients with early-stagecervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rateswere 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.

Clinical value of conventional magnetic resonance imaging combined with diffusion-weighted imaging in predicting pelvic lymph node metastasis of cervical cancer.

In cervical cancer (CC), the involvement of pelvis lymph nodes is a crucial factor for patients' outcome. We aimed to investigate the value of conventional magnetic resonance imaging (MRI) combined with diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) in predicting CC pelvic lymph node metastasis (PLNM). This retrospective study included CC patients who received surgical treatments. Surgical pathology results served as the gold standard for investigating the diagnostic performance of conventional MRI combined with DWI. We analyzed the association between tumor ADC and PLNM, as well as other pathological factors. The areas under the receiver operating characteristic curves (AUCs) for ADC in assessing PLNM and pathological factors were evaluated, and optimal cut-off points were obtained. A total of 261 CC patients were analyzed. PLNM patients had significantly lower tumor ADC (0.829 ± 0.144×10-3mm2/s vs. 1.064 ± 0.345×10-3mm2/s, p<0.0001), than non-PLNM CC. The agreement between conventional MRI combined with DWI and pathological results on PLNM diagnosis was substantial (Kappa=0.7031, p<0.0001), with 76% sensitivity, 94.31% specificity, and 90.8% accuracy. The AUC of tumor ADC was 0.703, and the optimal cut-off was 0.95×10-3 mm2/s. In multivariate analysis model 1, tumor ADC<0.95×10-3mm2/s was significantly associated with PLNM (OR, 2.83; 95%CI, 1.08-7.43; p= 0.0346) after adjusting for age and pathological risk factors. In multivariate analysis model 2, tumor ADC<0.95×10-3mm2/s (OR, 4.00; 95%CI, 1.61-9.89; p=0.0027), age<35 years old (OR, 2.93; 95%CI, 1.04-8.30; p=0.0428), increased tumor diameter on MRI (OR, 2.17; 95%CI, 1.18-3.99; p=0.0128), vaginal vault involvement on MRI (OR, 2; 95%CI, 1.002-3.99; p=0.0494) were independent predictors for PLNM. Tumor ADC<0.95×10-3mm2/s was significantly associated with higher risk of tumor diameter ≥4cm (OR, 2.60; 95%CI, 1.43-4.73; p=0.0017), muscular layer infiltration >1/2 (OR, 5.46; 95%CI, 3.19-9.34; p<0.0001), vaginal vault involvement (OR, 2.25; 95%CI, 1.28-3.96; p=0.0051), and lymphovascular space involvement (OR, 3.81; 95%CI, 2.19-6.63; p<0.0001). Conventional MRI combined with DWI had a good diagnostic performance in detecting PLNM. The tumor ADC value in PLNM patients was significantly lower than that in non-PLNM patients. Tumor ADC <0.95×10-3mm2/s, age <35 years old, increased tumor diameter on MRI, vaginal vault involvement on MRI were independent predictors for PLNM.

Desmoplasia in cervical cancer is associated with a more aggressive tumor phenotype

In cancer of the uterine cervix, the role of desmoplasia, i.e., peritumoral stromal remodeling characterized by fibroblast activation and increased extracellular matrix deposition, is not established. We conducted a retrospective cohort study based on data from 438 patients who had undergone surgical treatment for cervical cancer as part of the prospective Leipzig Mesometrial Resection study between 1999 and 2021. Using non-parametric tests, Kaplan–Meier plotting, and Cox regression modeling, we calculated the prognostic impact of desmoplasia and its association with other risk factors. Desmoplasia was present in 80.6% of cases and was associated with a higher frequency of lymphovascular space involvement (76.5 vs. 56.5%, p < 0.001) and venous infiltration (14.4 vs. 2.4%, p < 0.001). Lymph node metastasis (23.0 vs. 11.8%, p < 0.05) and parametrial involvement (47.3 vs. 17.6%, p < 0.0001) were also more common in patients with desmoplasia. The presence of desmoplasia was associated with inferior overall (80.2% vs. 94.5% hazard ratio [HR] 3.8 [95% CI 1.4–10.4], p = 0.002) and recurrence-free survival (75.3% vs. 87.3%, HR 2.3 [95% CI 1.2–4.6], p = 0.008). In addition, desmoplasia was associated with significantly less peritumoral inflammation (rho − 0.43, p < 0.0001). In summary, we link desmoplasia to a more aggressive phenotype of cervical cancer, reduced peritumoral inflammation, and inferior survival.

Adjuvant Concurrent Chemoradiotherapy vs. Radiotherapy Alone in Cervical Cancer Patients with Intermediate-Risk Factors after Radical Surgery

For early-stage cervical cancer patients with intermediate-risk factors, there is no consensus about whether postoperative concurrent chemoradiotherapy (CCRT) is superior to radiotherapy (RT) alone. We retrospectively reviewed medical records of stage I-IIA cervical cancer patients underwent radical surgery and postoperative RT or CCRT from June 2012 to December 2017. Patients with any of the high-risk factors including positive pelvic lymph node, positive resection margin, and parametrial invasion were excluded. Patients with any of the intermediate-risk factors including large tumor size (≥4cm), deep stromal invasion (≥1/2), and lymphovascular space involvement were included. 1:1 propensity score matching was performed to balance baseline variables between patients receiving RT and CCRT. A total of 350 patients were enrolled (84 underwent RT alone and 266 underwent CCRT). The median follow-up period was 50.4 months. For patients underwent RT alone and CCRT, the 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), the 5-year disease-free survival (DFS) rates were 90.6% and 91.4% (p = 0.733), respectively. 83 pairs of patients were enrolled based on propensity score matching. Similarly, there was no significant difference between OS or DFS rates of those matched patients. For patients with single intermediate-risk factor who received RT alone (n = 58) and CCRT (n = 132), the 5-year OS rates were 94.2% and 95.7% (p = 0.636), the 5-year DFS rates were 92.8% and 94.1% (p = 0.637). For patients with multiple intermediate-risk factors who received RT alone (n = 26) and CCRT (n = 134), the 5-year OS rates were 91.8% and 91.7% (p = 0.761), the 5-year DFS rates were 85.4% and 88.4% (p = 0.717). The cox regression analysis also indicated that adjuvant CCRT or RT was not an independent prognostic factor for OS or DFS. Otherwise, patients underwent CCRT seemed to develop a higher proportion of grade 3 or higher acute hematologic toxicities than RT group (45.5% and 14.3%, p<0.001). There was no significant difference in OS and DFS between cervical cancer patients with intermediate-risk factors receiving postoperative CCRT and RT alone. Patients underwent CCRT seemed to develop a higher proportion of severe hematologic toxicities than RT alone. To a certain extent, CCRT is not superior to RT alone for intermediate-risk patients.

Radiomics systematic review in cervical cancer: gynecological oncologists’ perspective

ObjectiveRadiomics is the process of extracting quantitative features from radiological images, and represents a relatively new field in gynecological cancers. Cervical cancer has been the most studied gynecological tumor for...

Role of tumor volume in endometrial cancer: An imaging analysis and prognosis significance.

To evaluate the prognostic value of tumor volume on preoperative MRI in endometrial cancer (EC) patients and its association with adverse prognostic factors and survival. A retrospective observational study with 127 consecutive patients with endometrioid EC was carried out between 2016 and 2021 at Juan Ramón Jiménez University Hospital, Huelva (Spain). All patients underwent preoperative magnetic resonance imaging (MRI) for local staging. The tumor volume was analyzed on MRI by two different methods: by measuring the three maximum diameters of the tumor according to an ellipse formula and by manual region of interest in different sections; the ratio between tumor volume and uterus volume was also calculated as a third tool. The relationships between volume, prognostic factors, and survival were analyzed. A total of 127 patients with endometroid EC underwent preoperative MRI and were included in the study. Tumor volume was significantly higher for deep myometrial invasion, cervical stromal involvement, infiltrated serosa, lymph node metastases, high-grade EC, and lymphovascular space involvement, advanced FIGO stage, and High Recurrence Risk Group (P < 0.001). ROC curves showed that tumor volume greater than 25 cm3 predicts lymph node metastases. Volume index greater than 17 cm3 was associated with reduced disease-free survival (P < 0.001) and overall survival (P < 0.003). Multivariate analysis showed that the greatest tumor volume had an independent impact on recurrence (odds ratio [OR]1.019, 95% confidence interval [CI] 1.005-1.032) and survival (OR 1.027, 95% CI 1.009-1.046). This study shows an important correlation between tumor volume on MRI and poor prognostic factors. Preoperative tumor volume on MRI is a valuable biomarker to be considered for management of EC.

Risk factors for lymph node metastasis and clinical outcomes in cervical cancer patients following primary radical hysterectomy: A single-center analysis of 1495 patients.

e17525 Background: Histopathological information obtained from surgical specimen is important to identify patients at increased risk for disease relapse and mortality. Lymph node metastasis (LNM) carries the highest impact on decreased survival in suspected early-stage cervical cancer. To further identify risk factors for LNM and prognosis in early stage cervical cancer patients is definitely necessary owing to the findings from different centers are inconsistent. Methods: A total 1495 cervical cancer patients were diagnosed with stage IA2-IIA cervical cancer according to clinical stage and underwent radical hysterectomy between April 2009 and December 2020. The stage of all the patients were reclassified after surgery according to FIGO 2018. We analyzed their clinicopathologic data to identify the risk factors for LNM. Among all the patients, the progression-free survival (PFS) and overall survival (OS) of 1109 patients between 2015 and 2020 were collected and analyzed. Results: The incidence of LNM is 18.8% in all 1495 patients, which increases with depth of cervical stromal invasion, tumor size, lymphovascular space involvement (LVSI) and vaginal wall invasion in univariate analysis. Multivariable analysis shows only stromal invasion (OR, 3.0; 95% CI, 1.7–5.3; P &lt; 0.001) and LVSI (OR, 4.9; 95% CI, 3.6-6.7; P&lt;0.001) are to be independent risk factors for LNM. In addition, the clinical parameters age is a protective factor against LNM in both univariate and multivariable analysis(P&lt;0.001). Among the 1109 patients, the median follow-up time is 49.7 months. Multivariate analyses using the Cox proportional hazards model show that LNM (HR, 8.5; 95% CI, 3.0-23.9; P&lt;0.001), stromal invasion (HR, 3.4; 95% CI, 2.2-5.4;P&lt;0.001) and special histologic type (HR, 3.2; 95% CI, 1.4-7.6; P=0.006) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. Conclusions: The pattern of cervical stromal invasion and presence LVSI, but not the primary tumor size, predict risk of nodal metastasis. Cervical stromal invasion, LNM and special histologic type (non-squamous cell carcinoma; non-Adenocarcinoma) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. [Table: see text]

Adjuvant Therapy in Early-Stage Cervical Cancer Patients with Intermediate-Risk Factors, Comparing Between Chemotherapy and Radiotherapy: A Systematic Review and Meta-Analysis

BACKGROUND: Patients with early-stage cervical cancer (ESCC) after radical hysterectomy surgery usually need additional adjuvant treatment, but it depends on the presence or absence of certain risk factors. Factors, such as large tumor size, deep stromal invasion, and lymphovascular space involvement, are classified as intermediate risks. Therefore, postoperative adjuvant concurrent chemo-radiotherapy (CRT) or radiotherapy (RT) is recommended for ESCC with risk factors. However, it remains controversial whether CRT is superior to RT as an adjuvant regimen for postoperative with risk factors. METHODS: A systematic search was performed within PubMed, Cochrane, Science Direct, and Google Scholar databases to research the outcome between CRT and RT in ESCC. Three reviewers independently reviewed titles, abstracts, and full article text to identify studies meeting inclusion and exclusion criteria. If there are any discrepancies, it will be resolved by discussion. In this analysis, the Newcastle–Ottawa scale was used to assess the risk of bias of non-randomized studies. We used review manager 5.4 to calculate the result of 95% CI for the outcomes using odds ratio (OR), random effect model was also used if there is heterogeneity. The primary endpoints of interest are recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 14 studies included in qualitative synthesis and meta-analysis with a total of 5.294 patients were identified. Patients who had RT after radical hysterectomy was found to significantly have a more favorable RFS rate with OR 0.57 95% CI (0.38–0.84), p = 0.005; I2 = 63%. Nine studies were found comparing the OS between adjuvant RT and adjuvant CRT in a patient with ESCC with intermediate risk, the result is quite similar favoring adjuvant RT with significantly better OS outcome OR 0.69 95% CI (0.54–0.87), p = 0.002; I2 =34%. 1.526 had hematologic toxicities, 797 were RT and 729 had CRT. The study showed RT had better outcomes with lesser toxicities (OR 0.11, 95% CI [0.03–0.44] p = 0.002; I2 = 91%). Non-hematological toxicity, with a total of 1.463 patients, 799 were RT and 664 had CRT. Random models were used due to heterogeneity. RT is significantly associated with lesser non- hematologic toxicities with OR 0.34, 95% CI (0.18–0.66) p = 0.001; I2 = 65%. DISCUSSION: During the last two decades, there were significant changes in practice to cure uterine cervical cancer. Based on the consistent results generated in several previous randomized controlled trials, cisplatin-based CCRT has become the standard treatment for advanced cervical cancer. A randomized prospective studies by Sedlis et al., randomized FIGO IB patients without residual tumor or involved lymph nodes but with two or more intermediate-risk factors later named the “Sedlis criteria” to receive observation or RT following radical surgery. Adjuvant RT led to a reduction of recurrence rates at the cost of an approximately 4% higher rate of grade 3/4 adverse events. There was no increase in OS but an improvement of long-term RFS. On the other hand, a study found that RFS and OS were significantly improved in the addition of chemotherapy, especially in patients with clinical-stage IA2, IB, and IIA with para-metric invasion, residual tumor and/or lymph node involvement. This study found that RT had better outcomes in RFS and OS, RT also had lesser hematologic toxicity and non-hematologic toxicity. After all, it is prudent to take into account the adverse events as well as the QOL for long-term survivors. CONCLUSION: Adjuvant RT shows a better outcome in RFS and OS. CRT is often associated with greater hematological and non-hematological toxicities. Further high-quality randomized clinical trials with larger sample size comparing the efficacy and toxicity of adjuvant CRT with RT are recommended.

Application of synthetic magnetic resonance imaging and DWI for evaluation of prognostic factors in cervical carcinoma: a prospective preliminary study.

To determine the values of quantitative metrics derived from synthetic MRI (SyMRI) and apparent diffusion coefficient (ADC) in evaluating the prognostic factors of cervical carcinoma (CC). In this prospective study, 74 patients with pathologically confirmed CC were enrolled. Pretreatment quantitative metrics including T1, T2 and ADC values were obtained from SyMRI and diffusion-weighted imaging (DWI) sequences. The values of all metrics were compared for different prognostic features using Student's t-test or Mann-Whitney U-test. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were utilized to evaluate the diagnostic performance of quantitative variables. T1 and T2 values of parametrial involvement (PMI)-negative were significantly higher than those of PMI-positive (p = 0.002 and < 0.001), while ADC values did not show a significant difference. The area under curve (AUC) of T1 and T2 values for identifying PMI were 0.743 and 0.831. Only the T2 values showed a significant difference between the lymphovascular space involvement (LVSI)-negative and LVSI-positive (p < 0.001), and the AUC of T2 values for discriminating LVSI was 0.814. The differences of T1, T2, and ADC values between the well/moderately and the poorly differentiated CC were significant (all p < 0.001). The AUCs of T1, T2 and ADC values for predicting differentiation grades were 0.762, 0.830, and 0.808. The combined model of all metrics proved to achieve good diagnostic performance with the AUC of 0.866. SyMRI may be a potential noninvasive tool for assessing the prognostic factors such as PMI, LVSI, and differentiation grades in CC. Moreover, the overall diagnostic performances of synthetic quantitative metrics were superior to the ADC values, especially in identifying PMI and LVSI. This is the first study to assess the utility of SyMRI-derived parameters and ADC value in evaluating the prognostic factors in CC.

Tumor-stroma interaction in cervical cancer: The prognostic importance of desmoplasia.

e17519 Background: During tumor growth, cancer cells can induce the formation of new extracellular matrix, mainly by activating peritumoral fibroblasts. This stromal reconfiguration has been termed desmoplasia. In pancreatic and ovarian cancer models, targeting desmoplasia therapeutically to normalize the microenvironment has recently shown promising results. We investigated the frequency and prognostic relevance of peritumoral desmoplasia, as well as its association with other prognostic factors such as lymph node involvement and parametrial tumor extension in cervical cancer patients. Methods: A retrospective cohort study based on data from the prospective monocentric observational Leipzig School Mesometrial Resection study was conducted. Cervical cancer patients staged IB1 to IVA according to the Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) who underwent primary surgery between 1999 and 2017 were included. Information regarding desmoplastic tumor reaction was retrospectively retrieved from the pathology reports. All other data had been collected prospectively during the trial period. Using non-parametric tests, we calculated the association of peritumoral desmoplasia with other common risk factors. To determine the prognostic significance of desmoplasia, we used the Kaplan-Meier estimator and performed multivariable Cox-regression modelling. Results: Overall, 355 patients were included. Desmoplasia was present in 298 cases and was associated with a significantly higher likelihood of lymphovascular space involvement (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.4 – 5.1, p = 0.001) and venous infiltration (OR 5.1, 95%-CI 1.3 – 44.9, p = 0.01). Lymph node metastasis was more common in patients with desmoplasia (OR 2.4, 95%-CI 1.2 – 5.0, p = 0.01), as was parametrial involvement (OR 3.5, 95%-CI 1.7 – 7.9, p = 0.0002). Interestingly, the presence of desmoplasia was not associated with larger tumor size. Patients with desmoplastic tissue reaction were significantly older than those without desmoplasia (median 41 years [inter quartile range 34 – 51] vs. 47 years [IQR 39-56], p = 0.009). These prognostically negative parameters in patients with desmoplastic disease translated into inferior overall (94.5% vs 80.5%, OR 3.9 [95%-CI 1.2 – 12.5], p = 0.02) and recurrence-free survival (86.8% vs. 74.2%, OR 2.3 [95%-CI 1.0 – 4.9], p = 0.04). A multivariable Cox-regression model including tumor size, patient age, and nodal status indicated that desmoplasia was an independent risk factor for overall death (OR 4.2, 95%-CI 1.03 – 17.5, p = 0.04). Conclusions: Desmoplastic stromal remodeling is associated with a more aggressive phenotype of cervical cancer and inferior survival. Targeting desmoplasia, especially in advanced disease when surgical treatment is not feasible, might be a promising treatment approach in the future.

Intraoperative Lymph Node Assessment (Touch Preparation Only) for Metastatic Breast Carcinoma in Neoadjuvant and Non-neoadjuvant Settings.

Touch preparation (TP) alone is discouraged for intraoperative lymph node (LN) assessment in the neoadjuvant setting (NAS) owing to overall low sensitivity in detecting metastatic breast cancer. To compare the sensitivity, specificity, and negative predictive value of intraoperative LN assessment via TP and examine potential causes of discrepancies along with the clinical, radiologic, and pathologic parameters in the NAS and non-neoadjuvant setting (NNAS). A total of 99 LNs from 47 neoadjuvant patients and 108 LNs from 56 non-neoadjuvant patients were identified. Discordant cases were reviewed retrospectively to reveal the discrepancy reasons. Clinical, radiologic, and pathologic data were obtained from chart review and the pathology CoPath database. The sensitivity, specificity, and negative predictive value of TP in NAS and NNAS were 34.2% versus 37.5%, 100% versus 100%, and 70.9% versus 90.2%, respectively. In NAS, discrepancy reasons were interpretation challenge due to lobular histotype, poor TP quality secondary to therapy-induced histomorphologic changes, and undersampling due to small tumor deposits (≤2 mm); the latter was the major reason in NNAS. More cases with macrometastasis were missed in NAS compared to NNAS (14 of 25 versus 1 of 10). The parameters associated with discrepancy were lobular histotype, histologic grade 2, estrogen receptor positivity, HER2 human epidermal growth factor receptor 2 negativity, multifocality, and pathologic tumor size greater than 10 mm in NAS; and lymphovascular space involvement and pathologic tumor size greater than 20 mm in NNAS. In NAS, intraoperative TP alone should be used very cautiously owing to a high false-negative rate of macrometastasis, especially for patients with invasive lobular carcinoma and known axillary LN metastasis before neoadjuvant therapy.

Identification and Biopsy of Sentinel Lymph Node in Early-Stage Cervical Carcinoma: Diagnostic Accuracy and Clinical Utility.

BackgroundDue to the subsequent complications of pelvic lymphadenectomy in patients with early-stage cervical cancer, the sentinel lymph node (SLN) technique has been increasingly employed. This study aimed to investigate the detectability of SLN using methylene blue and explore the diagnostic accuracy of SLN biopsy.MethodologyA study was conducted from September 2015 to August 2018 and included 90 women with cervical cancer, FIGO (International Federation of Gynecology and Obstetrics-2009) stage IA1-IIA1. Methylene blue was injected intracervically. Any detected dyed nodes were sent for frozen section biopsy, followed by bilateral pelvic lymphadenectomy. The predictive ability of SLN was evaluated in statistical terms after comparison of intraoperative biopsy and final histopathology.ResultsThe sensitivity, specificity, false-negative rate, positive predictive value, and negative predictive value (NPV) were 55.6%, 95.1%, 4.9%, 55.6%, and 95.1%, respectively. The SLN performance in patients with tumor size ≤2.2 cm, negative lymphovascular space involvement, and depth of stromal invasion ≤5 mm was superior (sensitivity 100%, specificity 93.5%, NPV 100%).ConclusionsThe SLN technique with blue dye alone is a feasible and adequate alternative to systematic lymphadenectomy in early-stage cervical cancer in selected patients, given that a strict algorithm is applied.

Implications of Isolated Para-Aortic Lymph Node Metastasis in Endometrial Cancer: A Large-Scale, Multicenter, and Retrospective Study

Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy.Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated.Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6–59.9], 74.2 95% CI: 65.6–81.4), and 45.8% (95% CI: 38.7–53.2), respectively.Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.

The Impact of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Epithelial Ovarian Cancer

OBJECTIVE: This study aims to investigate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with epithelial ovarian cancer. STUDY DESIGN: Between January 2012 and December 2018, the data and preoperative levels of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio of 116 epithelial ovarian cancer patients were retrospectively collected. The association of these relevant markers with outcomes was analyzed. RESULTS: The difference was observed concerning optimal and suboptimal debulking in platelet-to-lymphocyte ratio ratios (p=0.04). Lymphovascular space involvement was significantly associated with higher platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio ratios (p&lt;0.0001). Patients with ascites and lymph node involvement had a higher platelet-to-lymphocyte ratio ratio (p=0.007 and p=0.004). In recurrences, higher ratios of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were observed (p=0.03 and p=0.02). The analysis revealed that platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were not independent prognostic factors for recurrence (p=0.783 and p=0.391). Regarding mortality, platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were not independently prognostic (p=0.621 and p=0.830). It was determined that neutrophil-to-lymphocyte ratio &gt;2.45 (HR 0.714, CI 0.622-0.794, p&lt;0.0001) and platelet-to-lymphocyte ratio &gt;179.4 (HR 0.736, CI 0.646-0.814, p&lt;0.0001) could predict the presence of recurrence with a certain sensitivity and specificity, and for predicting the death, a neutrophil-to-lymphocyte ratio of &gt;2.45 had a sensitivity of 78.26% (95% CI: 56.3 to 92.5%) and a specificity of 54.84% (95%CI: 44.2 - 65.2) (p=0.03). CONCLUSION: The evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is important in obtaining prognostic information before surgery. However, no significant association between the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio with survival was identified.

Comparison of Outcomes and Prognostic Factors Between Early-Stage Cervical Adenocarcinoma and Adenosquamous Carcinoma Patients After Radical Surgery and Postoperative Adjuvant Radiotherapy.

PurposeNo consensus has been reached regarding the survival difference between cervical adenocarcinoma (ADC) and adenosquamous carcinoma (ASC) patients. The purpose of this study was to compare survival outcomes and prognostic factors between early-stage ADC and ASC patients.Patients and MethodsWe retrospectively reviewed stage IB-IIA patients with ADC and ASC who underwent radical hysterectomy and postoperative radiotherapy between June 2012 and December 2017.ResultsA total of 125 patients were enrolled in our study (97 with ADC and 28 with ASC). The median follow-up period was 53.4 months. Compared with ASC patients, patients with ADC tended to have a higher proportion of positive pelvic lymph nodes (7.1% and 26.8%, respectively; p = 0.028). The most common site of distant metastasis was the lung, followed by the intestine and colon. The 5-year overall survival (OS), disease-free survival (DFS), pelvic control, and distant control rates for ADC and ASC patients were 83.6% and 92.0% (p = 0.349), 77.5% and 87.7% (p = 0.279), 81.8% and 96.2% (p = 0.121), and 88.3% and 87.7% (p = 0.948), respectively. Parametrial invasion was a prognostic factor for OS. Lymphovascular space involvement was a prognostic factor for DFS.ConclusionADC patients were more likely to have positive pelvic lymph nodes than those with ASC. There was no significant difference in survival outcomes between patients with ADC and ASC.

Conization and lymph node evaluation in low-risk cervical cancer. Is it time to avoid radical surgery? Retrospective series and literature review

ObjectivesTo evaluate the oncologic and obstetric outcomes of patients with low-risk cervical cancer who underwent conization and lymphatic evaluation to preserve fertility. MethodsData were collected retrospectively from September 2013 to February 2021. Eligibility criteria included Women with cervical cancer (aged <45 years) who underwent fertility preservation treatment, [stage IA1 with positive lymphovascular space invasion (LVSI), stage IA2, or stage IB1 (≤2 cm) with less <10 mm cervical stromal invasion, according to the International Federaltion of Gynecology and Obstetrics (FIGO) 2018 staging system] aged ≤45 years who wished to preserve their fertility were included in this study. All patients were treated with cervical conization(s) and laparoscopic lymph node evaluation [pelvic lymphadenectomy and/or sentinel lymph node (SLN) mapping]. Oncologic and obstetric outcomes were evaluated. ResultsOverall, 31 patients met the inclusion criteria; 15 (48.3%) women were nulliparous. There were 8 IA1LVSI+ (25.8%), 11 IA2 (35.4%) and 12 IB1 (31.7%) tumours, according to 2018 FIGO stage classification. Most patients had squamous cell carcinoma (77.4%). Lymphovascular space involvement was found in thirteen patients (41.9%). Reconization was performed in 17 (54.8%) patients, of which 6(35.2%) were done due to compromised margins, 4(23.5%) for margins under than 3 mm, 3(17.6%) for unreported or coagulated margins and 4(23.5%) because previous conization was done in another institution and we could not obtain the paraffin blocks for pathology review. Twenty patients had MRI and eleven CT scan. Nine (30%) patients had a complete bilateral pelvic lymph node dissection, 9 (26.6%) had SLN mapping with pelvic lymphadenectomy, and 13 (43.3%) had SLN mapping alone after bilateral SLN identification at surgery. After a median follow-up of 41.4 months (range 2–90 months), no recurrences have been detected. In terms of obstetrial outcome, 11 patients attempted pregnancy and 9 became pregnant. First-trimester miscarriage occurred in one patient. Five patients delivered at term by caesarean section, one of them requiring hysterectomy at the time of delivery. Pathology did not show residual disease. Two patients had a vaginal delivery at 38 weeks. One pregnancy is still ongoing. ConclusionCervical conization with lymph node assessment by SLN mapping/lymphadenectomy is an oncologic safe procedure in patients with low-risk cervical cancer.

Topographic distribution of lymph node metastasis in patients with stage IB1 cervical cancer: an analysis of 8314 lymph nodes

BackgroundSystematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment.MethodsA total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification.ResultsTotally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases.ConclusionsThe incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI.

Oncologic and obstetric outcomes after simple conization for fertility-sparing surgery in FIGO 2018 stage IB1 cervical cancer

ObjectiveConization/simple trachelectomy is feasible in patients with early-stage cervical cancer. Retrospective data suggest that conization with negative lymph nodes could be a safe option for these patients. This study aims...

High-grade endometrial stromal sarcoma versus undifferentiated uterine sarcoma: a Turkish uterine sarcoma group study-001

Prognostic factors associated with high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS) have not been distinctly determined due to the repetitive changes in the World Health Organization (WHO) classification. We aimed to compare clinicopathologic features and outcomes of patients with HGESS with those of patients with UUS. A multi-institutional, retrospective, cohort study was conducted including 71 patients, who underwent surgery at 13 centers from 2008 to 2017. An experienced gynecopathologist from each institution re-evaluated the slides of their own cases according to the WHO2014 classification. Factors associated with refractory/progressive disease, recurrence or death were examined using logistic regression analyses. Kaplan-Meier method and log-rank test were used for survival comparisons. The median disease-free survival (DFS) for HGESS and UUS was 12months and 6months, respectively. While the median overall survival was not reached in HGESS group, it was 22months in the UUS group. Kaplan-Meier analyses revealed that patients with UUS had a significantly poorer DFS than those with HGESS (p = 0.016), although OS did not differ between the groups (p = 0.135). Lymphovascular-space involvement (LVSI) was the sole significant factor associated with progression, recurrence or death for HGESS (Hazard ratio: 9.353, 95% confidence interval: 2.539-34.457, p = 0.001), whereas no significant independent factor was found for UUS. UUS has a more aggressive behavior than HGESS. While no significant predictor of prognosis was found for UUS, LVSI is the sole independent prognostic factor for HGESS, with patients 9.3 times more likely to experience refractory/progressive disease, recurrence or death.

A modified technique of laparoscopic radical trachelectomy combined with extracorporeal cervical amputation through a mini-laparotomy

Radical trachelectomy is an optional fertility-sparing treatment for early-stage cervical cancer, and recently, the minimally invasive approach (MIA) has become a major trend in radical trachelectomy. MIA radical trachelectomy requires a more careful surgical technique to avoid tumor spillage and exposure of the cancerous tissue under carbon dioxide pneumoperitoneum to reduce the risk of recurrence. We present a case of a 33-year-old nulliparous woman with stage IB1 cervical cancer who underwent MIA radical trachelectomy through a combination of laparoscopic surgery and mini-laparotomy, mainly to prevent postoperative complications and tumor spread during cervical amputation. A Papanicolaou test suggested the diagnosis of squamous cell carcinoma of the cervix without any symptoms such as atypical bleeding. The subsequent biopsy revealed squamous cell carcinoma with stromal invasion of the cervix. Cervical amputation was performed extracorporeally through a small incision in the lower abdomen. There were no perioperative complications. The patient was discharged on postoperative day 13. The final pathological evaluation revealed residual microinvasive cancer of the endocervical canal with clear margins, no lymphovascular space involvement, and 27 negative lymphatic nodes. The joint of the neo-cervix and vagina had healed completely without erosion or stenosis of the cervical canal, and no problems occurred during sexual intercourse. No cancer recurrence or menstrual disorders have been reported in the short postoperative period of 6 months. The surgical technique of laparoscopic radical trachelectomy combined with extracorporeal cervical amputation may be an acceptable alternative to reduce the risk of recurrence by preventing intraperitoneal tumor spillage.