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Summary Objective Recent studies have shown that minimally invasive surgery (MIS) is associated with a higher recurrence rate in patients with early-stage cervical cancer. In this study, we aim to report the survival outcomes of patients with early-stage cervical cancer who received MIS, performed in a single center by the same surgeon. Methods Eligible participants included patients with early-stage cervical cancer in stage IA1 with lymphovascular space invasion (LVSI+), IA2, and IB1. The surgeries were carried out by a single surgeon and survival outcomes of the 137 patients were evaluated retrospectively. Results The median follow-up time for the 137 patients was 53 (25–94) months, with the five-year disease-free survival (DFS) rate of 96.4% and the five-year overall survival (OS) rate of 96.8%. Among them, six (4.38%) patients relapsed and four (2.92%) of whom died. The five-year DFS rate was significantly higher in patients with tumor≤2 cm in size than in those with tumor >2 cm (P = 0.013), however, with no significant difference in the five-year OS rate (P = 0.219). Conclusion According to the existing literature and the results of this study, for MIS, the proficiency levels of a surgeon may be associated with survival outcomes of cancer patients. Tumor size may also be an important factor affecting survival outcomes of cervical cancer patients.

Radical surgery after cervical conization is a common approach for the treatment of cervical cancer. In some cases, disease progression is observed after positive margins at conization, but the effect of conization on disease progression remains unclear. Thus, the aim of this study was to investigate the clinical outcomes of positive margins at conization in cervical cancer. A total of 101 patients who underwent cervical conization before radical hysterectomy and pelvic lymph node dissection were considered eligible by reviewing medical records. The association between the positive margins and patient outcomes, including subsequent lymph node metastasis, was evaluated. The rate of lymphovascular space invasion (LVSI) positivity at radical surgery was significantly higher in patients with positive margins (p = 0.017) than in those with negative margins, although there was no significant difference in the rate of pelvic lymph node metastasis (p = 0.155). Moreover, there was no significant difference in the overall survival or progression-free survival between the two groups (p = 0.332 and 0.200, respectively). A positive margin at conization presented no significant prognostic disadvantage; thus, diagnostic conization is one of the most suitable treatment options for early-stage cervical cancer that is difficult to accurately assess.

Background Invasive Papillary Carcinomas (IPC) are rare and account for approximately 0.5% of all invasive breast carcinomas. Most of them are seen in post-menopausal women and have a good prognosis. These tumors lack the myoepithelial cell layer (MCL) within the papillae or at the periphery of the tumor with areas showing stromal invasion or invasion into lymphovascular spaces. Immunohistochemistry (IHC) for myoepithelial cells and basement membrane is essential for the diagnosis of invasive cancer. Case presentation We present a rare case of IPC in a 74-year-old woman who presented with complaints of gradually increasing painless retroaerolar mass in the left breast of two months duration. The mass was irregular, having an oblong as well an adjacent high density mass lesion on mammography. Ultrasound (US), and Magnetic Resonance Imaging (MRI) helped in the diagnosis of the possibility of a malignant breast lesion. Left-sided modified radical mastectomy was performed and the specimen was histopathologically diagnosed as Invasive Papillary carcinoma. Immunohistochemistry confirmed the diagnosis. Conclusions Invasive Papillary Carcinomas of the breast are rare cancers in post-menopausal women. We have highlighted the role of Mammography, US, and MRI in early diagnosis so that timely management is possible.

Introduction: The expression of matrix metalloproteinase-9 (MMP-9), MMP-13, and tissue inhibitor of metalloproteinases (TIMP-1) in head and neck squamous cell carcinoma (HNSCC) could be a useful predictor of tumour differentiation, nodal metastasis, and invasiveness. We conducted this study to ascertain the correlation between the expression of these markers and differentiation of tumour cells. Materials and Methods: A prospective observational study was conducted in a tertiary care center. Forty-three cases of proven HNSCC were recruited after obtaining informed consent. Using the surgically excised specimen, tumour differentiation and invasiveness were assessed and correlated with rates of expression of the markers. Chi-square test was done to correlate immunohistochemical (IHC) marker positivity and the degree of differentiation of the tumour, lymph node metastasis, and invasiveness. Results: MMP-9, MMP-13, and TIMP-1 were expressed in 72%, 34%, and 18% of cases, respectively. p16 expression was not found in any of the cases. MMP-13 expression correlated with poorer differentiation of the tumour (p = 0.03), and relatively younger age at diagnosis (p = 0.01). However, there was no correlation with lymphovascular or perineural invasion or lymph node metastasis. Discussion: In our study, MMP-13 expression correlated with poorer tumour differentiation and younger age at diagnosis, giving indirect evidence of tumour aggressiveness. IHC markers can provide additional information to prognosticate HNSCC. Identifying potential targets for newer biological therapy is essential in the Indian population as there are biological differences in cancer behavior. Increased expression of the proteolytic MMP-13 correlated with poorer differentiation of HNSCC.

Background The aim of this study was to analyze overall survival in endometrial cancer patients’ FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). Methods A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. Results In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18–1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95–1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. Conclusion The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

Background: Axillary web syndrome (AWS) is a frequent complication after surgery for breast cancer, but its lymphatic involvement is not definitively established. Here we report the results of lymphoscintigraphic investigations in patients with AWS. Methods and Findings: We conducted a retrospective, single-center review of lymphoscintigraphic investigations performed in 46 patients with AWS that was either clinically obvious or suspected. Of this group, 23 patients had two investigations with a mean interval of 19 weeks between them (range, 6-98 weeks). Results of the lymphoscintigraphic investigations, which were performed according to a well-standardized protocol, were classified into four patterns: normal; functional lymphatic insufficiency only (no lymphatic vascular morphologic abnormality); lymphovascular blockade without collateralization; and vascular collateralization and/or dermal backflow. Of the 46 patients, on the first lymphoscintigraphic investigation, four (8.6%) had a normal pattern, seven (15.2%) had functional lymphatic insufficiency only, four (8.6%) had lymphovascular blockade without collateralization, and 31 (67.3%) had vascular collateralization and/or dermal backflow. Among patients who underwent two investigations, four of the five who had only functional lymphatic insufficiency at the first investigation had developed vascular collateralization and/or dermal backflow by the second. The three patients who had lymphovascular blockade without collateralization at the first examination had also progressed to collateralization and/or dermal backflow at the second. None of the 15 patients who initially had vascular collateralization and/or dermal backflow showed any reversal at the second examination. Conclusions: Our analysis confirms the lymphatic nature of AWS and shows the lymphoscintigraphic patterns and evolutions of the lymphatic lesions with potential therapeutic implications. The retrospective review of our database is approved by the institutional ethics committee under number 2048.

Highlights • It is considered that adenocarcinoma has the stepwise continuum of progression. • It is rare for adenocarcinomas with lepidic growth lacking invasion to be >3.0 cm. • We report a rare case of 6 cm diameter adenocarcinoma without an invasive component. • The tumour harboured uncommon EGFR mutation detected on next-generation sequencing. • Next-generation sequencing could be useful for detecting uncommon genes of tumour., Background According to the WHO classification, adenocarcinoma in situ (AIS) is a localised small (≤3 cm) adenocarcinoma whose growth is restricted to neoplastic cells along pre-existing alveolar structures, lacking stromal, lymphovascular, or pleural invasion. There is no evidence to define AIS as having a tumour size of ≤3 cm. It is extremely rare for adenocarcinomas with pure lepidic growth lacking invasion to be >3.0 cm. The biological characteristics of these large AISs should be revealed. Presentation of case The patient was an 82-year-old asymptomatic woman. Chest computed tomography showed a 6-cm-diameter pure ground-glass opacity in the left lower lung. The patient underwent lobectomy. On histologic examination, the tumour was restricted to neoplastic cells along pre-existing alveolar structures, lacking stromal, vascular, alveolar space, and pleural invasion. Papillary patterns were absent. Initially, the histopathological diagnosis was AIS, but the total tumour diameter exceeded 3 cm. The final pathological diagnosis was lepidic adenocarcinoma lacking an invasive component and harbouring an EGFR exon 20 insertion V774_C775insHV mutation using next-generation sequencing (NGS). Conclusion We report a rare case of lepidic adenocarcinoma with a total tumour diameter of 6 cm and without an invasive component. Although EGFR mutations are oncogenic driver mutations, AISs have fewer EGFR mutations than invasive adenocarcinomas do. An adenocarcinoma that progresses to AIS, not stepwise progression, might have uncommon mutations and might be another type of adenocarcinoma. NGS could be useful for detecting uncommon genes that reveal the biological characteristics of AIS, and may contribute to the validation of next TNM classification.

Background Postoperative pathologic risk factors (PRFs) could increase the recurrence rate in early-stage uterine cervical squamous cancer (ECSC). Our study intended to explore the efficiency of 18F-FDG PET/CT for assessing the pathologic risk status (PRS) in ECSC patients. Methods This retrospective study was performed in 240 ECSC patients with stage IA2-IIA2 (FIGO 2009), who underwent preoperative PET/CT scans and subsequent radical surgery between January 2010 and July 2015. Intermediate-risk (tumour diameter ≥ 4 cm, stromal invasion depth ≥ 1/2, lymphovascular space invasion (LVSI)), and high-risk factors (parametria involvement, positive surgery margin, pelvic lymph node metastasis) were confirmed by postoperative pathology. Patients with none of these PRFs were at a low risk for relapse. One of these PRFs was defined as positive risk. The relationship between each PRF and 18F-FDG uptake was analysed by t-test. Chi-square tests and logistic regression analyses were used to determine the efficiency of PET/CT parameters for assessing the PRS. The area under the curve (AUC) was used as an indicator for predictive efficiency. Results Patients with higher SUVmax (p p p Conclusions Preoperative 18F-FDG PET/CT had an independent predictive value for PRS in ECSC.

Objectives: The objectives of this study were (1) to estimate the frequency of preoperative abnormal cervical cytology (CC), (2) to explore correlations between preoperative CC and specific clinicopathological prognostic factors (tumor stage, endometrioid grade, myometrial invasion, lymphovascular space involvement, cervical involvement, and recurrence), and (3) to examine the impact of preoperative CC on disease-free survival (DFS) and overall survival (OS) in Saudi patients with endometrioid-type endometrial cancer (EC). Materials and Methods: A retrospective cross-sectional study was conducted at a tertiary hospital in Saudi Arabia. The study’s inclusion criteria included: (1) patients who underwent staging operation for EC from 2010–2014, (2) patients who had preoperative CC results within 3 months before staging operation, and (3) patients with final histopathological diagnosis of endometrioid-type EC. Results: Hundred and sixteen patients (n = 116) met the study’s inclusion criteria. CC results were abnormal in 46 patients (39.7%). Patients with abnormal CC had statistically significant higher rates of unfavorable Grades II–III tumor and cervical involvement than patients with normal CC (P = 0.004, chi-square test). There were no statistically significant differences (log-rank test) between patients with normal and abnormal CC with regard to DFS (P = 0.525) and OS (P = 0.166). Multivariate analyses of DFS and OS (Cox proportional hazards model) failed to show preoperative CC as a significant independent prognostic factor of DFS and OS (P > 0.05). Conclusion: The frequency of abnormal preoperative CC in patients with endometrioid-type EC is not uncommon. Abnormal CC correlates with poor prognostic factors, namely high tumor grade and cervical involvement. Preoperative CC is not a significant independent prognostic factor of survival.

In endometrioid cancer cases, the depth of myometrial invasion, the lymphovascular space invasion (LVSI) and the microcystic, elongated, and fragmented (MELF) glands type of invasion are predictors for a metastasis. Although the intermediate grade papillary endometrioid adenocarcinoma of the endometrium is currently not included in the latest classification of the tumors in the female reproductive system, its existence provokes an interest due to the necessity to perform differential diagnosis against other endometrioid tumors. Hereby presented is a case of papillary endometrioid carcinoma of intermediate grade with invasion in leiomyoma, expressed via LVSI and MELF syndrome with intact myometrium. Morphological and immunohistochemical algorithms have been performed.

Background Lymph node metastasis (LNM) has a strong influence on the prognosis of patients with early gastric cancer (EGC). The aim of this study was to reveal the incidence of LNM and evaluate risk factors for LNM to determine the appropriate treatment for EGC in a Chinese population. Methods Patients who underwent radical gastrectomy with lymph node dissection for EGC between 2012 and 2017 were retrospectively analyzed. Univariate and multivariate analyses were conducted to identify clinicopathological features that were risk factors for LNM. Results A total of 1033 patients with EGC were enrolled. Of these patients, 668 (64.7%) were men, and 365 (35.3%) were women, ranging in age from 19 to 82 years (mean 56.9 ± 10.9 years). LNM was detected in 173(16.7%) patients with EGC. Among 508 patients with mucosal cancer, 44 (8.7%) patients had LNM. In 525 patients with submucosal cancer, the incidence of LNM was 24.6% (129/525). The age, gender, tumor size, type of differentiation, Lauren classification, and lymphovascular and perineural invasion showed a significant correlation with the rate of LNM in EGC by univariate and multivariate analyses. Patients with submucosal gastric cancer had an older age, a higher proportion of proximal lesion, larger tumor size, more frequent lymphovascular invasion, perineural invasion, and more LNM than patients with mucosal gastric cancer. Conclusions Our study revealed a relatively high incidence of LNM in EGC, compared with Japanese and Korean cohorts. Female sex, large tumor size, undifferentiated-type, and lymphovascular invasion were independent risk factors for LNM in EGC. Radical gastrectomy with lymphadenectomy should be performed in EGC patients with a high risk of LNM.

Background/Aims: We aimed to investigate the proportion of and risk factors for residual cancer and/or lymph node metas tasis after surgery was performed because of high-risk pathological features in endoscopic resection specimen of suspected superficial submucosal colorectal cancer (SSMC). Methods: We reviewed medical records of 497 patients (58.8±9.8 years, 331 males) undergoing endoscopic resection of suspected SSMC. High-risk pathological features included: deep submucosal cancer invasion ≥1,000 μm; positive lymphovascular and/or perineural invasion; poorly differentiated adenocarcinoma; and positive resection margin. We investigated the occurrence of additional surgery and residual cancer and/or lymph node in volvement in the surgical specimen. Results: En bloc resection was performed in 447 patients (89.9%). High-risk pathological features were detected in 372 patients (74.8%). Additional surgery was performed in 336 of 372 patients with high-risk patho logical features. Of these, 47 surgical specimens (14.0%) showed residual cancer and/or lymph node metastasis. Piecemeal re section was more common in those with residual cancer and/or lymph node involvement than those without (9/47 [19.1%] vs. 24/289 [8.3%], P=0.032). Positive resection margin was also significantly associated with positive residual cancer and/or lymph node involvement. As the number of high-risk pathological features increased, the risk of regional lymph node metastasis in creased proportionally (P=0.002). Conclusions: High-risk pathological features were frequently detected after endoscopic re section of suspected SSMC while residual cancer and/or lymph node metastasis were not commonly present in the additional surgical specimen. Further optimized strategy for proper endoscopic management of suspected SSMC is necessary. (Intest Res 2020;18:96-106)

International audience; BACKGROUND: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on overall survival (OS) and recurrence-free survival (RFS) in patients managed for stage I-IIa clear cell carcinoma, mucinous, low-grade serous and low-grade endometrioid ovarian cancer MATERIAL AND METHODS: Retrospective multicentre study of the research group FRANCOGYN between January 2001 and December 2018. All patients managed for stage I-IIa clear cell carcinoma, mucinous /low grade serous and endometrioid ovarian cancer and for whom the presence of histological slides for the review of LVSI was available, were included. Patient’s characteristics with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A cox analysis for OS and RFS analysis were performed in all population. RESULTS: Over the study period, 133 patients were included in the thirteen institutions. Among them, 12 patients had LVSI (9%). LVSI was an independent predictive factor for poorer Overall and recurrence free survivals. LVSI affected OS (p

OBJECTIVES: We aimed to evaluate if the revised staging according to FIGO-2018 in early-stage cervical cancer correctly predicts the risk for nodal metastases.METHODS: We reallocated 245 women with early-stage cervical cancer from FIGO-2009 to FIGO-2018 stages using data from a national, prospective cohort study on sentinel lymph node (SLN) mapping. We used univariate and multivariate binary regression models to investigate the association between FIGO-2018 stages, tumor characteristics, and nodal metastases.RESULTS: Stage migration occurred in 54.7% (134/245) (95% CI 48.2-61.0), due to tumor size or depth of invasion (71.6%, 96/134) and nodal metastases (28.4%, 38/134). Imaging preoperatively upstaged 7.3% (18/245); seven had nodal metastatic disease on final pathology. Upstaging occurred in 49.8% (122/245) (95% CI 43.4-56.2%) and downstaging to FIGO-2018 IA stages in 4.9% (12/245) (95% CI 2.6-8.4). The tumor size ranged from 3.0-19.0 mm in women with FIGO-2018 IA tumor characteristics, and none of the 14 women had nodal metastases. In multivariate analysis, risk factors significantly associated with nodal metastases were FIGO-2018 ≥ IB2 (RR 5.01, 95% CI 2.30-10.93, p < 0.001), proportionate depth of invasion >2/3 (RR 1.88, 95% CI 1.05-3.35, p = 0.033), and lymphovascular space invasion (RR 5.56, 95% CI 2.92-10.62, p < 0.001).CONCLUSIONS: The FIGO-2018 revised staging system causes stage migration for a large proportion of women with early-stage cervical cancer. Women who were downstaged to FIGO-2018 IA stages did not have nodal metastatic disease. The attention on depth of invasion rather than horizontal dimension seems to correctly reflect the risk of nodal metastases.

Although skin melanoma (SKM) represents only one-quarter of newly diagnosed skin malignant tumors, it presents a high mortality rate. Hence, new prognostic and therapeutic tools need to be developed. This study focused on investigating the prognostic value of the subcellular expression of BRAF, KRAS, and KIT in SKM in correlation with their gene-encoding interactions. In silico analysis of the abovementioned gene interactions, along with their mRNA expression, was conducted, and the results were validated at the protein level using immunohistochemical (IHC) stains. For IHC expression, the encoded protein expressions were checked on 96 consecutive SKMs and 30 nevi. The UALCAN database showed no prognostic value for the mRNA expression level of KRAS and BRAF and demonstrated a longer survival for patients with low mRNA expression of KIT in SKMs. IHC examinations of SKMs confirmed the UALCAN data and showed that KIT expression was inversely correlated with ulceration, Breslow index, mitotic rate, and pT stage. KRAS expression was also found to be inversely correlated with ulceration and perineural invasion. When the subcellular expression of BRAF protein was recorded (nuclear vs. cytoplasmatic vs. mixed nucleus + cytoplasm), a direct correlation was emphasized between nuclear positivity and lymphovascular or perineural invasion. The independent prognostic value was demonstrated for mixed expression of the BRAF protein in SKM. BRAF cytoplasmic predominance, in association with KIT’s IHC positivity, was more frequently observed in early-stage nonulcerated SKMs, which displayed a low mitotic rate and a late death event. The present study firstly verified the possible prognostic value of BRAF subcellular localization in SKMs. A low mRNA expression or IHC cytoplasmic positivity for KIT and BRAF might be used as a positive prognostic parameter of SKM. SKM’s BRAF nuclear positivity needs to be evaluated in further studies as a possible indicator of perineural and lymphovascular invasion.

BackgroundMyometrial invasion has been demonstrated to correlate to clinicopathological characteristics and prognosis in endometrial cancer. However, not all the studies have the consistent results and no meta-analysis has investigated the association of myometrial invasion with lymphovascular space invasion (LVSI), lymph node metastasis (LNM), recurrence, and overall survival (OS). Therefore, a meta-analysis was performed to evaluate the relationship between myometrial invasion and clinicopathological characteristics or overall survival in endometrial cancer.Materials and MethodsA search of Pubmed, Embase, and Web of Science was carried out to collect relevant studies from their inception until June 30, 2021. The quality of each included study was evaluated using Newcastle–Ottawa scale (NOS) scale. Review Manager version 5.4 was employed to conduct the meta-analysis.ResultsA total of 79 articles with 68,870 endometrial cancer patients were eligible including 9 articles for LVSI, 29 articles for LNM, 8 for recurrence, and 37 for OS in this meta-analysis. Myometrial invasion was associated with LVSI (RR 3.07; 95% CI 2.17–4.35; p < 0.00001), lymph node metastasis (LNM) (RR 4.45; 95% CI 3.29–6.01; p < 0.00001), and recurrence (RR 2.06; 95% CI 1.58–2.69; p < 0.00001). Deep myometrial invasion was also significantly related with poor OS via meta-synthesis of HRs in both univariate survival (HR 3.36, 95% CI 2.35–4.79, p < 0.00001) and multivariate survival (HR 2.00, 95% CI 1.59–2.53, p < 0.00001). Funnel plot suggested that there was no significant publication bias in this study.ConclusionDeep myometrial invasion correlated to positive LVSI, positive LNM, cancer recurrence, and poor OS for endometrial cancer patients, indicating that myometrial invasion was a useful evaluation criterion to associate with clinical outcomes and prognosis of endometrial cancer since depth of myometrial invasion can be assessed before surgery. The large scale and comprehensive meta-analysis suggested that we should pay more attention to myometrial invasion in clinical practice, and its underlying mechanism also deserves further investigation.

Background: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) was carried out. Patients with IA to IB2 2018 FIGO stage, who underwent preoperative conization before SLN biopsy were included. Results: Between January 2005 and July 2012, 161 patients from 25 French centers fulfilled the inclusion criteria. Macrometastases, micrometastases and Isolated tumor cells (ITCs) were found in 4 (2.5%), 6 (3.7%) and 5 (3.1%) patients respectively. Compared to negative SLN patients, patients with micrometastatic and macrometastatic SLN were more likely to have lymphovascular space invasion (LVSI) (60% vs. 29.5%, p = 0.04) and deep stromal invasion (DSI) ≥ 10 mm (50% vs. 17.8%, p = 0.04). Among the 93 patients with DSI &lt, 10 mm and absence of LVSI on conization specimens, three patients (3.2%) had ITCs and only one (1.1%) had micrometastases. Conclusions: Patients with DSI &lt, 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient’s risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).

Vascular endothelial growth factor receptors (VEGFRs) are part of the evolutionarily conserved VEGF signalling pathways that regulate the development and maintenance of the body’s cardiovascular and lymphovascular systems. VEGFR3, encoded by the FLT4 gene, has an indispensable and well-characterized function in development and establishment of the lymphatic system. Autosomal dominant VEGFR3 mutations, that prevent the receptor functioning as a homodimer, cause one of the major forms of hereditary primary lymphoedema; Milroy disease. Recently, we and others have shown that FLT4 variants, distinct to those observed in Milroy disease cases, predispose individuals to Tetralogy of Fallot, the most common cyanotic congenital heart disease, demonstrating a novel function for VEGFR3 in early cardiac development. Here, we examine the familiar and emerging roles of VEGFR3 in the development of both lymphovascular and cardiovascular systems, respectively, compare how distinct genetic variants in FLT4 lead to two disparate human conditions, and highlight the research still required to fully understand this multifaceted receptor.

Endometrial cancer is the most common gynecologic malignancy in Europe and usually diagnosed in its initial stage owing to early symptoms of abnormal bleeding. There is no population screening for this disease, although it can sometimes be accidentally diagnosed in asymptomatic patients. Our study aims to determine differences in clinical and tumor characteristics between an asymptomatic and symptomatic group of patients. This unicentric prospective observational study took place in University Hospital Brno between January 2016 and December 2019. A total of 264 patients met inclusion criteria (26% asymptomatic, 74% with reported symptoms). We did not find a statistically significant difference in clinical characteristics (menopausal status, parity, age, BMI, and serum level of CA 125) between groups. According to ultrasound examination, bleeding tumors were larger (19.5 vs. 12.7 mm, p ≤ 0.001). Definitive histology results indicated more frequent lymphovascular space invasion (p &lt, 0.001), along with deep myometrial (p = 0.001) and cervical (p = 0.002) invasion. There was no difference in advanced stages of the tumor. We did not substantiate statistically significant difference in immunohistochemical profile (estrogen and progesterone receptors, L1 cell adhesion molecule, tumor protein p53), which is relevant for tumor recurrence risk and survival capacity. Our conclusions affirmed that bleeding occurs more often among patients with local tumor invasion into the myometrium and cervical stroma. Final International Federation of Gynecology and Obstetrics (FIGO) stage, histology, and immunohistochemical characteristics do not significantly affect symptom appearance.

The authors have raised an interesting and relevant question. Traditionally, and supported by data from many early randomized studies, patients with endometrial carcinoma and postsurgery diagnosis of pT1A/stage IA grade 1 endometrioid endometrial carcinoma with myometrial invasion and no

A 73-year-old man visited our hospital for the treatment of an early gastric cancer (GC) lesion. We performed en bloc resection using endoscopic submucosal dissection (ESD) for his GC lesion. The present GC lesion was Epstein-Barr virus (EBV)-associated poorly differentiated-type adenocarcinoma invading into the submucosal layer. Recently, accumulating data has shown that the risk of lymph node metastasis from early EBV GC without local lymphovascular infiltration is low. The present patient has been in good health for over three years since ESD. Some cases of early EBV GC with invasion into the submucosal layer may be candidates for further extension of the ESD criteria.

Background Vulvar extramammary Paget disease is a rare chronic condition, that presents with non-specific symptoms such as pruritus and eczematous lesions. Because most of these lesions are noninvasive, the distinction between primary and secondary Paget disease is crucial to management. Case presentation We report an unusual case of vulvar Paget disease associated with massive dermal vascular embolization, cervicovaginal involvement and metastasis to inguinal and retroperitoneal lymph nodes. The intraepithelial vulvar lesion had a classical appearance and was accompanied by extensive component of dermal lymphovascular tumor emboli, similar to those observed in inflammatory breast carcinoma. Immunohistochemical analysis revealed that the lesion was secondary to high-grade urothelial cell carcinoma. The patient had a history of superficial low-grade papillary urothelial carcinoma of the bladder, which had appeared 2 years before the onset of vulvar symptoms. Conclusions Eczematoid vulvar lesions merit careful clinical examination and biopsy, including vulva mapping and immunohistochemistry. The information obtained may help to define and classify a particular presentation of Paget disease. Noninvasive primary lesions do not require the same aggressive approaches required for the treatment of invasive and secondary disease.

Objective To evaluate the necessity of adjuvant therapy and other prognostic factors in high-grade uterine corpus-confined endometrial cancer (EC) with lymphadenectomy performed. Materials and methods This study included 120 patients who had endometrioid-type grade 3, serous-type, clear cell-type, and undifferentiated-type EC and underwent lymphadenectomy. Results Patients with high-grade uterine corpus-confined EC who underwent lymphadenectomy were evaluated. The modality of adjuvant therapy performed was not a predictor for the site of recurrence. The loco-regional recurrence rate decreased from 9.5% to 3.8% in patients who received radiotherapy. However, this difference was not statistically significant (p=0.206). In addition, performing adjuvant chemotherapy did not alter the risk of extrapelvic recurrence. Only International Federation of Gynecology and Obstetrics 2009 stage was significant in the univariate analysis. On the other hand, age, tumor type, number of removed lymph nodes, presence of myometrial and lymphovascular space invasion, tumor size and adjuvant therapy modality were not related with disease-free survival. Conclusion Performing adjuvant therapy and therapy modality does not improve oncologic outcomes in intermediate and high-risk patients. However, radiotherapy reduced the risk of local recurrence by more than 50%. Vaginal brachytherapy was efficient as external beam radiotherapy. Therefore, vaginal brachytherapy should be used for these patients in order to reduce loco-regional recurrence even if it is not reported to be effective on disease-free survival.

Background SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC. Methods We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs. Results A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancerspecific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022). Conclusions We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.

Maffucci syndrome is a rare nonhereditary disorder comprising of lymphovascular malformations and multiple enchondromas, which may be associated with several internal malignancies. This report describes a new association of Maffucci syndrome with pedal synovial sarcoma. Our case is also remarkable as lymphangioma circumscriptum is the sole lymphovascular component, which has been rarely reported. The aim of this report is to generate awareness about this rare condition and also highlight the importance of screening for malignancies in this disorder.

Rectal neuroendocrine tumors (NETs) are rare, with an incidence of 0.17%, but they represent 12% to 27% of all NETs and 20% of gastrointestinal NETs. Although rectal NETs are uncommon tumors, their incidence has increased over the past few years, and this is probably due to the improvement in detection rates made by advanced endoscopic procedures. The biological behavior of rectal NETs may be different: factors predicting the risk of metastases have been identified, such as size and grade of differentiation. The tendency for metastatic diffusion generally depends on the tumor size, muscular and lymphovascular infiltration, and histopathological differentiation. According to the current European Neuroendocrine Tumor Society (ENETS) guidelines, tumors that are smaller than 10 mm and well differentiated are thought to have a low risk of lymphovascular invasion, and they should be completely removed endoscopically. Rectal NETs larger than 20 mm have a higher risk of involvement of muscularis propria and high metastatic risk and are candidates for surgical resection. There is controversy over rectal NETs of intermediate size, 10–19 mm, where the metastatic risk is considered to be 10–15%: assessment of tumors endoscopically and by endoanal ultrasound should guide treatment in these cases towards endoscopic, transanal, or surgical resection.

International audience; Background: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer.Patients and methods: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.Results: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (

ObjectiveEvidence on micrometastases and isolated tumor cells as factors associated with non-vaginal recurrence in low- and intermediate-risk endometrial cancer is limited. The goal of our study was to investigate risk factors for non-vaginal recurrence in low- and intermediate-risk endometrial cancer.MethodsRecords of all patients with endometrial cancer surgically managed at the Mayo Clinic before sentinel lymph node implementation (1999–2008) were reviewed. We identified all patients with endometrioid low-risk (International Federation of Gynecology and Obstetrics (FIGO) stage I, grade 1 or 2 with myometrial invasion ResultsAmong 1303 women, we identified 321 patients with low-risk (n=236) or intermediate-risk (n=85) endometrial cancer (median age 65.4 years; 266 (82.9%) stage IA; 55 (17.1%) stage IB). Of the total of 321, 13 patients developed non-vaginal recurrence (Kaplan–Meier rate 4.7% by 60 months; 95% CI 2.1% to 7.2%): 11 hematogenous/peritoneal and two para-aortic and distant lymphatic. Myometrial invasion and lymphovascular space invasion were univariately associated with non-vaginal recurrence. In these patients, the original hematoxylin/eosin slides review confirmed all 646 pelvic and para-aortic removed lymph nodes as negative. The ultrastaging of 463 pelvic lymph nodes did not identify any occult metastases (prevalence 0%; 95% CI 0% to 22.8% considering 13 patients; 95% CI 0% to 0.8% considering 463 pelvic lymph nodes).ConclusionThere were no occult metastases in pelvic lymph nodes of patients with low- or intermediate-risk endometrial cancer with non-vaginal recurrence. Myometrial invasion and lymphovascular space invasion appear to be associated with non-vaginal recurrence.

STUDY OBJECTIVE To investigate the factors associated with poorer oncologic outcomes in patients undergoing laparoscopic radical hysterectomy (LRH) for early stage cervical cancer. DESIGN Multicenter retrospective study. SETTING Three gynecologic oncology referral centers. PATIENTS Patients with International Federation of Gynecology and Obstetrics 2009 stage IA (positive lymphovascular space invasion)-IB1 cervical cancer between January 2006 and June 2018. INTERVENTIONS LRH (Piver type II-III hysterectomies). Lymph-node dissection was accomplished according to the tumor characteristics. MEASUREMENTS AND MAIN RESULTS Surgical and oncologic outcomes were analyzed. Overall, 186 patients met the inclusion criteria, 16 (8.6%) experienced a recurrence, and 9 (4.8%) died of the disease (median follow-up period 37.9 months). Surgery-related complications did not influence disease-free survival. All the recurrences (16/16; 100%) occurred in patients with stage IB1 disease (p = .02), and 15 (93.7%) in cases involving tumors ≥2 cm. No association between positive lymph node and recurrence was detected (p =.82). Patients who had a preoperative diagnosis through conization (93; 50%) had a significantly lower rate of recurrence than those who underwent cervical biopsy (93; 50%): 1/93 (1.1%) vs 15/93 (16.1%); p

Simple Summary The purpose of modifying a tumor staging system is to incorporate already well-established prognostic factors, allowing one to stratify cases and leading to tailored treatment approaches. Although lymphovascular space invasion (LVSI) has been described as an independent risk-factor of recurrence in early-stage cervical cancer and defined intermediate and high-risk cervical cancer according to the ESGO (European Society of Gynaecological Oncology) guidelines, this factor remains controversial and was not included in the last revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification. The aim of the present study was to determine whether LVSI has an impact on the prognosis of IB1 patients according to 2018 FIGO classification through two French prospective multicentric cohorts. Our results highlighted that LVSI was associated with a significantly decreased 5-year DFS in IB1 2018 FIGO stage compared to negative LVSI. Particular attention should be paid to LVSI status in early-stage cervical cancer for a more precise risk assessment and we suggest that LVSI may be considered in the new 2018 FIGO classification. Abstract Background: The aim of this study was to assess the prognostic impact of Lymphovascular space invasion (LVSI) in IB1 stage of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification for cervical cancer. Methods: A secondary analysis of two French prospective multicentric trials on Sentinel Lymph node biopsy for cervical cancer was performed. Patients with 2009 FIGO IB1 stage who underwent radical surgery between January 2005 and July 2012 from 28 French expert centers were included. The stage was modified retrospectively according to the new 2018 FIGO staging system. Results: According to the 2009 FIGO classification, 246 patients had IB1 disease stage and fulfilled the inclusion criteria. The median follow-up was 48 months (4–127). Twenty patients (8.1%) experienced a recurrence, and the 5-year Disease Free Survival (DFS) was 90.0%. Compared to 2018 IB1 staged patients, new IB2 had significantly decreased 5-year DFS, 78.6% vs. 92.9%, p = 0.006 whereas IIIC patients had similar 5-year DFS (91.7%, p = 0.95). In the subgroup of patients with FIGO 2018 IB1 stage, the presence of LVSI was associated with a significant decrease in DFS (82.5% vs. 95.8%, p = 0.04). Conclusions: LVSI is associated with decreased 5-year DFS in IB1 2018 FIGO stage and LVSI status should be considered in early-stage cervical cancer for a more precise risk assessment.

Purpose Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poor prognosis in gastric cancers. In this work, we aimed to investigate the potential role of computed tomography (CT) texture analysis in predicting LVI and PNI in patients with tubular gastric adenocarcinoma (GAC) using a machine learning (ML) approach. Methods Sixty-eight patients who underwent total gastrectomy with curative (R0) resection and D2-lymphadenectomy were included in this retrospective study. Texture features were extracted from the portal venous phase CT images. Dimension reduction was first done with a reproducibility analysis by two radiologists. Then, a feature selection algorithm was used to further reduce the high-dimensionality of the radiomic data. Training and test splits were created with 100 random samplings. ML-based classifications were done using adaptive boosting, k-nearest neighbors, Naive Bayes, neural network, random forest, stochastic gradient descent, support vector machine, and decision tree. Predictive performance of the ML algorithms was mainly evaluated using the mean area under the curve (AUC) metric. Results Among 271 texture features, 150 features had excellent reproducibility, which were included in the further feature selection process. Dimension reduction steps yielded five texture features for LVI and five for PNI. Considering all eight ML algorithms, mean AUC and accuracy ranges for predicting LVI were 0.777-0.894 and 76%-81.5%, respectively. For predicting PNI, mean AUC and accuracy ranges were 0.482-0.754 and 54%-68.2%, respectively. The best performances for predicting LVI and PNI were achieved with the random forest and Naive Bayes algorithms, respectively. Conclusion ML-based CT texture analysis has a potential for predicting LVI and PNI of the tubular GACs. Overall, the method was more successful in predicting LVI than PNI.

Simple Summary The claudin (CLDN) family, the backbone of tight junctions, consists of more than 20 members in humans, and exhibits distinct expression patterns in tissue- and cell-type-specific manners. Among the CLDN members, CLDN6 is primarily expressed in diverse embryonic epithelial cells. It is also aberrantly expressed in various types of cancers, but its significance remains obscure. In the present study, we generated a highly specific anti-human CLDN6 monoclonal antibody, and assessed the prognostic significance of aberrant CLDN6 expression in endometrial cancer tissues. This study indicates that high CLDN6 expression in endometrial cancer relates to several clinicopathological factors and is an independent prognostic factor. The established monoclonal antibody could be a valuable tool to evaluate CLDN6-expressing tumors. Abstract Background: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. Results: The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological type, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). Conclusions: It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

Purpose To evaluate the capabilities of two-dimensional magnetic resonance imaging (MRI)-based texture analysis features, tumor volume, tumor short axis and apparent diffusion coefficient (ADC) in predicting histopathological high-grade and lymphovascular space invasion (LVSI) in endometrial adenocarcinoma. Materials and methods Seventy-three women (mean age: 66 ± 11.5 [SD] years; range: 45–88 years) with endometrial adenocarcinoma who underwent MRI of the pelvis at 1.5-T before hysterectomy were retrospectively included. Texture analysis was performed using TexRAD® software on T2-weighted images and ADC maps. Primary outcomes were high-grade and LVSI prediction using histopathological analysis as standard of reference. After data reduction using ascending hierarchical classification analysis, a predictive model was obtained by stepwise multivariate logistic regression and performances were assessed using cross-validated receiver operator curve (ROC). Results A total of 72 texture features per tumor were computed. Texture model yielded 52% sensitivity and 75% specificity for the diagnosis of high-grade tumor (areas under ROC curve [AUC] = 0.64) and 71% sensitivity and 59% specificity for the diagnosis of LVSI (AUC = 0.59). Volumes and tumor short axis were greater for high-grade tumors (P = 0.0002 and P = 0.004, respectively) and for patients with LVSI (P = 0.004 and P = 0.0279, respectively). No differences in ADC values were found between high-grade and low-grade tumors and for LVSI. A tumor short axis ≥ 20 mm yielded 95% sensitivity and 75% specificity for the diagnosis of high-grade tumor (AUC = 0.86). Conclusion MRI-based texture analysis is of limited value to predict high grade and LVSI of endometrial adenocarcinoma. A tumor short axis ≥ 20 mm is the best predictor of high grade and LVSI.

Neuroendocrine neoplasms (NENs) are the most common tumor of the appendix and have an excellent prognosis. Appendiceal tumors diagnosed between 1989 and 2019 were reviewed, and clinical data were collected from patient files. Part of the series was immuno-profiled for markers related to cell cycle proliferation and/or senescence-type, apoptotic, and metastatic potential. Appendix NENs were detected in 74 patients, with 0.47% of incidence per appendectomy. The median age of the patients was 21.5 years, with two age peaks of incidence at 17.0 and 55.2 years. The median tumors size was 5.8 mm, and most were smaller than 10 mm. Lymphovascular and perineural invasion, as well as necrosis, was associated with larger tumor size. G1 tumors composed 96.0% of the cohort. The presence of moderate/strong p16 and the absent/low Bcl-2 expression was frequently observed and associated with a smaller size. This study represents one of the largest cohorts and with a long follow-up. For tumors smaller than 10 mm appendicectomy was sufficient as a curative procedure, as revealed by the good outcome. This series presented a 100% disease-free survival. The indolent phenotype of appendix NENs is supported by the expression of markers that point towards a strong inhibition of cell replication and growth inhibition., This study was supported by FCT—Fundação para a Ciência e a Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior by a research contract to João Vinagre (CEECIND/00201/2017). Further funding was obtained from the project “Advancing cancer research: from basic knowledge to application” NORTE-01-0145-FEDER-000029: “Projetos Estruturados de I & D & I”, funded by Norte 2020—Programa Operacional Regional do Norte. Additional funding was obtained from the project PTDC/MED-ONC/31438/2017 (The other faces of Telomerase: Looking beyond tumor immortalization), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI) and by Portuguese funds through FCT under project POCI-01-0145-FEDER-016390: CANCEL STEM”.

Objective: The aim of this study was to evaluate clinical and morphological features related to nodal involvement in appendiceal neuroendocrine tumors (NETs), to identify patients who should be referred for oncological radicalization with hemicolectomy. Background: Appendiceal NETs are usually diagnosed accidentally after appendectomy; the indications for right hemicolectomy are currently based on several parameters (ie, tumor size, grading, proliferative index, localization, mesoappendiceal invasion, lymphovascular infiltration). Available guidelines are based on scarce evidence inferred by small, retrospective, single-institution studies, resulting in discordant recommendations. Methods: A retrospective analysis of a prospectively collected database was performed. Patients who underwent surgical resection of appendiceal NETs at 11 tertiary Italian centers, from January 1990 to December 2015, were included. Clinical and morphological data were analyzed to identify factors related to nodal involvement. Results: Four-hundred fifty-seven patients were evaluated, and 435 were finally included and analyzed. Of them, 21 had nodal involvement. Grading G2 [odds ratio (OR) 6.04], lymphovascular infiltration (OR 10.17), size (OR 18.50), and mesoappendiceal invasion (OR 3.63) were related to nodal disease. Receiver operating characteristic curve identified >15.5mm as the best size cutoff value (area under the curve 0.747). On multivariate analysis, grading G2 (OR 6.98), lymphovascular infiltration (OR 8.63), and size >15.5mm (OR 35.28) were independently related to nodal involvement. Conclusions: Tumor size >15.5mm, grading G2, and presence of lymphovascular infiltration are factors independently related to nodal metastases in appendiceal NETs. Presence of 1 of these features should be considered an indication for oncological radicalization. Although these results represent the largest study currently available, prospective validation is needed.

Objective To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). Methods This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. Results 428 patients were included in the analysis. With a median follow-up of 56 months (1–162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01–1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34–20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11–0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01–1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58–24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12–0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13–0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39–17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. Conclusions In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.