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Gastric carcinoma with lymphoid stroma (GCLS), a rare subset of gastric cancer, has a low frequency of lymphovascular invasion and a relatively better prognosis compared with conventional gastric cancer. We herein report a rare case of early GCLS successfully treated by endoscopic submucosal dissection alone. The lesion was located in the upper gastric body and approximately 9 mm in size. We assessed that the lesion was within an absolute indication for endoscopic resection. We performed endoscopic submucosal dissection and succeeded in en bloc resection. A histopathological assessment disclosed that the carcinoma was poorly differentiated with massive infiltration of lymphocyte and invaded the submucosal layer massively at 1000 μm in depth. There were no visible lymphovascular invasions in the specimen. Since the Epstein-Barr virus (EBV)-encoded small RNA in situ hybridization revealed that cancer cells were positive for EBV, the patient was finally diagnosed with EBV-positive GCLS. We persuaded the patient to receive an additional surgery; however, the patient refused to undergo it. The patient has been followed for more than 5 years without recurrence.

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.

This review summarises the anatomy and lymphatic systems around the pelvic floor. We investigated the lymphovascular network in the anorectal region, focusing on the hiatal ligament, which comprises smooth muscle fibres derived from the longitudinal muscle and connecting the anal canal and coccyx, and the endopelvic fascia, which seems to comprise collagen and elastic fibres. During rectal surgery, endopelvic fascia is recognized as a sheet of fascia covering the levator ani muscle. Endopelvic fascia is extensively attached to the smooth muscle fibres diverging from the longitudinal muscle of the rectum. Analysis of the lymphovascular network using submucosal India ink injection and indocyanine green fluorescence imaging suggests a functional lymphatic flow between rectal muscle fibres and hiatal ligament and endopelvic fascia. Precise analysis of the lymphatic systems of fascial organization around the pelvic floor may be useful in formulating therapeutic strategies for low rectal cancer.

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.

ObjectiveThe role and type of adjuvant therapy for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIA grade 1 endometrioid endometrial adenocarcinoma are controversial. This retrospective cohort study aimed to determine associations between adjuvant therapy use and survival among patients with stage IIIA grade 1 endometrial cancer.MethodsPatients who underwent primary surgery for stage IIIA (FIGO 2009 staging) grade 1 endometrial cancer between January 2004 and December 2016 were identified in the National Cancer Database. Demographics and receipt of adjuvant therapy were compared. Overall survival was analyzed using Kaplan–Meier curves, log-rank test, and multivariable Cox proportional hazard models.ResultsOf 1120 patients, 248 (22.1%) received no adjuvant treatment, 286 (25.5%) received chemotherapy alone, 201 (18.0%) radiation alone, and 385 (34.4%) chemotherapy and radiation. Five-year overall survival rate was 83.0% (95% CI 80.1% to 85.6%). Older age, increasing comorbidity count, and lymphovascular space invasion status were significant negative predictors of survival. Over time, there was an increasing rate of chemotherapy (45.4% in 2004–2009 vs 69.2% in 2010–2016; pConclusionsThe use of adjuvant chemotherapy for the treatment of stage IIIA grade 1 endometrial cancer increased over time and was associated with improved overall survival compared with radiation alone or chemoradiation. Patients with lymphovascular space invasion may benefit from combination therapy.

Objectives: We aimed to investigate the clinical and pathological factors of our patients who were diagnosed with endometrial cancer in terms of prognosis. With this study, we present our 10 years of surgical experience in endometrial carcinoma cases. Material and methods : Four hundred twelve patients with endometrial carcinoma who applied to our center between 2010–2019 and that we followed up were evaluated retrospectively. Results : Most of the tumors were low-grade endometrioid malignancies. Non-endometrioid types accounted for 12.1% of cases. Lymph node dissection was performed in 395 of 412 patients (95.9%). 66 (16.01%) of the 412 patients died during the follow-up period in the study sample. Higher OS and DFS rates were associated with endometrioid histological types, FIGO stage, absence of lymphovascular space invasion, lower grade and less than 50% myometrial invasion (p < 0.05). 5-year OS at stage 1, 2, 3, 4 was found as 88.9 ± 2.2%, 65.5 ± 10.8%, 49.4 ± 0.79% and 23.7 ± 0.97% respectively. 5-year DFS at stage 1, 2, 3, 4 was found as 84.1 ± 2.6%, 65.5 ± 10.8%, 47.7 ± 0.78% and 23.7 ± 0.97% respectively. In univariate analysis, Age, tumor histology, FIGO stage, histological grade, LVSI, positive peritoneal cytology, cervical involvement, myometrial invasion and not receiving adjuvant therapy were defined as prognostic factors. Conclusions: Age, grade, FIGO stage, myometrial invasion, histological type, LVSI involvement, cervical involvemet, positive peritoneal cytology and not receiving adjuvant therapy are important prognostic factors for progression-free survival and overall survival in patients diagnosed with endometrial cancer.

Objective: The aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC). Methods: We enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1–G2, with myometrial invasion

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

Women diagnosed with early-stage (FIGO 1) endometrial cancer, grade 1 and 2 can have a good prognosis. Most of these women can be treated successfully with a hysterectomy and bilateral salpingo-oophorectomy and without the additional adjuvant treatment that is accompanied by more risks for complications. However, when recurrence does occur, the consequences can be dire. Accurate decisions must therefore be made by surgeons to avoid either under- or over-treatment. Risk and patient stratification for tailoring treatment still need further improvement. Both histopathology and genetic variants could be integrated into the decision process if relevant factors were identified. Morphological features and the presence of selected genetic mutations in isolated malignant endometrial epithelial cells from these tumors were analyzed in a strictly defined cohort of FIGO 1, grade 1 and 2 low-risk endometrial cancer. Their presence in this cohort, their relation to recurrence, and the association between histopathological features and mutations were determined. This analysis was performed using archival formalin-fixed paraffin-embedded tissue, complete re-evaluation of histopathological features, laser capture microdissection of epithelial cells, and a polymerase chain reaction-based mutational screening assay. Twenty-one women with recurrence, after initial identification as low-risk endometrial cancer, were compared with 20 matched control women. The histological marker of lymphovascular invasion was significantly associated with recurrence. There was also a very high prevalence of mutations in CTNNB1 gene, occurring in 50% of this cohort. PTEN mutations were also observed in 27.8% of cases and PIK3CA mutations in 22.2%; none of these mutations were significantly related to recurrence. This study supports the importance of lymphovascular space invasion to identify women with significant risk for recurrence in initially low-risk, early-stage endometrial cancer. It also identifies CTNNB1 as a significant mutation in early-stage disease, and although it may not represent a marker for recurrence its high prevalence in early stage disease could have relevance for both pathogenesis and early treatment.

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.

It is unclear whether postoperative wound infections after head and neck cancer surgery are associated with cancer progression.Patients undergoing surgery for oral cancer from 1998 to 2011 were reviewed. Univariable analyses and multivariable were performed. Propensity scores were used to create matched cohorts for infection and non-infection groups. Neutrophil-to-lymphocyte ratios (NLR) were determined prior to surgery and at the time of infection.Of 551 patients with oral cancer treated with surgery, 98 developed wound infections (18%). Tumor factors associated with wound infections included higher T and N category, extranodal extension, depth of invasion, lymphovascular and perineural invasion (p 0.02 for all). On univariable analysis, wound infection was a predictor for recurrence free survival (p 0.001), locoregional control (p = 0.01), and distant control (p 0.001). Wound infection was not a predictor of overall survival (p = 0.88), recurrence free survival (p = 0.17), locoregional control (p = 0.79) or distant control (p = 0.18) on multivariable analysis. Using a propensity score matched cohort of 83 patients with and without infection, wound infection was not associated with recurrence free survival (p = 0.21), overall survival (p = 0.71), and locoregional control (p = 0.84), although there was a trend towards increased distant metastases (p = 0.10). Patients with wound infection had a greater preoperative NLR as well as a greater rise in the NLR after surgery, but these were not associated with survival or recurrence.Patients with wound infections have more adverse pathologic features. However, wound infection was not associated with poorer cancer outcomes although a trend towards increased distant metastases should be investigated.

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.

Objective To identify predictors of extensive lymphatic dissemination and distant recurrences in node-positive endometrial cancer (EC). Methods Clinicopathologic data were collected of patients who had fully staged EC with at least 1 positive lymph node. Permanent sections of metastatic lymph nodes were reviewed; metastases were characterized according to size (≤2 mm and >2 mm) and location in the lymph node (intra- vs extracapsular). Risk of occurrence of multiple pelvic and para-aortic lymph node dissemination was calculated by combining risk factors identified at multivariate analysis. Results Of 96 patients, 85 had positive pelvic nodes, of whom 71 (83.5%) had high-volume metastases. In the presence of both macrometastasis in the pelvic basin (odds ratio [OR], 13.42; [95% CI, 2.44–73.83]) and uterine serosal involvement of the tumor at final pathologic evaluation (OR, 11.84 [95% CI, 1.22–115.11]), multiple pelvic node dissemination occurred in 91.7% of cases (vs 7.7% in the absence of both). Concomitant presence of pelvic macrometastasis, lymphovascular space invasion (LVSI), and extracapsular invasion led to 85.7% occurrence of para-aortic involvement (vs 11.1% if no factors present). LVSI was independently associated with nonvaginal recurrences (hazard ratio, 2.62 [95% CI, 1.33–5.16]). Conclusions Presence of high-volume metastases in the pelvic lymph nodes is associated with concomitant presence of multiple positive pelvic nodes, as well as para-aortic node involvement. LVSI is associated with both para-aortic node involvement and occurrence of nonvaginal relapses. In this era of sentinel lymph node mapping, these factors may help predict the extent of lymphatic dissemination in EC.

To evaluate the risk factors for pelvic lymph node metastasis (LNM) in endometrial cancer (EC). Clinicopathological characteristics and preoperative laboratory results were retrospectively analyzed in 393 surgically staged patients with EC (January 2014–February 2019). Pelvic LNM was detected in 45 (11.5%) patients. Univariate analysis showed that increased preoperative levels of human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), and decreased absolute lymphocyte count (ALC), as well as non-endometrioid histology, grade 3 tumor, deep myometrial invasion, vaginal or para-uterine involvement, adnexal involvement, positive peritoneal cytology, and lymphovascular space invasion (LVSI) were risk factors for pelvic LNM (All p

Metastasis of tumour cell greatly contributes to the cause of mortality. Tumour-associated macrophage (TAM) and the intercellular adhesion molecule 1 (ICAM-1) were associated with metastases of breast carcinoma. However, the relationship between lymphatic vessel densities and invasion with TAM and ICAM-1 remained unclear. The aim of this study was to investigate the relationship of lymphovascular densities and invasions with patient’s clinicopathological data. The roles of TAM and ICAM-1 influencing lymphovascular invasions were also investigated. Haematoxylin and eosin (H&E) and immunohistochemical (IHC) staining on a consecutive section of 37 formalin fixed-paraffin embedded (FFPE) breast invasive carcinoma samples were carried out. The D2-40, CD34, CD163, and ICAM-1 antibodies were used to stain lymphatic vessel, blood vessel, TAM, and ICAM-1 receptor, respectively. The total lymphatic vessel density (LVD) was significantly reduced on increased tumor size (p=0.045). The increase of intra-tumoral LVD and lymphatic vessel invasion (LVI) was significantly associated with human epidermal growth factor receptor 2 (HER2) negative status (p=0.022 and p=0.05, respectively). The percentage of LVI was higher than blood vessel invasion (BVI) in 18.5%. Lymphovascular invasions detected in H&E were missed in 49.76% compared with those detected in IHC-stained tissues (206/410). ICAM-1 scores were significantly associated with non-triple negative breast cancer (non-TNBC) (p=0.008). ICAM-1 is significantly overexpressed on non-TNBC sample. Therefore, ICAM-1 might be clinically useful as a targeted molecule for non-TNBC patients. In histological reporting, in addition to H&E staining, IHC staining using D2-40 and CD34 should be considered to increase the accuracy of diagnosis.

Context: Vulval cancer surgery has become more conservative and it is important to understand whether resection margins alone influence recurrence rates or whether other prognostic factors should be considered when planning treatment. Aims: The aim of this study is to define factors that predict vulval cancer recurrence, enabling development of a recurrence prediction model. Settings and Design: This was a Aretrospective descriptive analysis of new vulval squamous cell carcinoma cases in a gynecological oncology center (January 1, 2007 to December 31, 2013). Subjects and Methods: Analysis of tumor characteristics and treatments. Patient outcomes were recorded, identifying recurrences, and subsequent interventions. Statistical Analysis Used: Univariable and multivariable logistic regression tools applied to determine recurrence risk factors. Results: Seventy patients underwent primary vulval surgery. Bilateral groin node dissection was performed in 26/70 (37.1%) cases and unilateral groin node dissection in 9/70 (12.9%) cases. 57/70 (82%) cases had a negative vulval resection margin, with 67%

INTRODUCTION: Neuroendocrine tumors (NETs) are neoplasms that arise from neuroendocrine cells that have properties of both neuronal and endocrine cells. NETs are most common in the small intestine, rectum, and the appendix and frequently termed carcinoid. PRESENTATION OF CASE: A 30-year-old male presented with abdominal pain and tenderness in the RLQ. Computerized tomography revealed findings consistent with acute appendicitis. The patient underwent an uneventful laparoscopic appendectomy for an acutely inflamed appendicitis. Histopathological examination, showed a 0.5 cm well-differentiated neuroendocrine tumor of the distal appendix, with clear margins. The mitotic rate was 2 cm in size, if there is evidence of lymphovascular or meso-appendiceal invasion, with mesenteric lymph node metastases, or for intermediate or high-grade tumors. CONCLUSION: We present the case of a 30-year old male that presented with an appendiceal, well-differentiated NET that manifested as appendicitis and laparoscopic appendectomy was performed. The appendix was resected with clear margins. Given appropriate markers appendectomy can be curative.

Objectives: To evaluate the correlation between lymphovascular space invasion (LVSI) indicating lower uterine segment involvement (LUSI) in endometrioid endometrial cancer and lymph node metastasis based on the lymphatic drainage difference between the uterine corpus and the lower segment. Material and methods: Patients who underwent staging surgery for endometrioid endometrial cancer between January 2010 and January 2019 at our institution were reviewed. The clinicopathologic findings and LUSI status of the patients were compared with their LVSI and lymph node metastasis status. Results: Of the 253 patients included in this study, 49 (19.4%) had LUSI. Among these patients, none of the 31 LVSI-negative patients had metastatic lymph node involvement. However, of the 18 LVSI-positive patients, half had metastatic lymph node involvement; this difference was significant (p < 0.05). Conclusions: The significant correlation between LVSI and lymph node metastasis in LUSI-positive cases indicates that pathologists should also focus on LVSI findings in the frozen examination required for the decision of staging surgery in patients with endometrioid endometrial cancer limited to the uterus. This is especially important in patients with a lower uterine segment involvement.

Mucinous adenocarcinoma (MAC) is defined by the presence of extracellular mucin covering more than 50% of the tumour area; however, MAC is histologically heterogeneous and some cases exhibit signet ring cell components. The aim of this study was to determine the prognostic impact of such variable morphology. A total of 299 consecutive MAC patients who underwent curative surgery were included. MACs were classified into four categories according to the predominant pattern of floating tumour cells: strips (27.1%), clusters (51.8%), signet ring cells (6.7%), and mixed clusters and signet ring cells (14.4%). In addition, we categorised MACs according to the relative amount of mucin. MACs with signet ring cell component were clearly associated with poor overall and recurrence-free survivals. Moreover, MACs with more than 50% signet ring cell component showed particularly poor clinical outcome just like non-mucinous signet ring cell carcinoma. MACs with a greater amount of extracellular mucin were associated with poor recurrence-free survival, independent of the pathological stage. In addition, lymphovascular and perineural invasion, advanced pathological stage, and old age at diagnosis were also prognostic factors for poor overall survival. MACs with more than 50% signet ring cell component should be classified as signet ring cell carcinoma and the presence of signet ring cells should be included in the pathology report of MACs with 10-50% signet ring cell component.

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.

Background and objective: Circulating tumor cells (CTCs) can be classified into three phenotypes based on epithelial-to-mesenchymal transition (EMT) markers, including epithelial CTCs, mesenchymal CTCs, and mixed phenotypic CTCs. This study is aimed to analyze the correlation between CTC phenotypes and the clinicopathological features of patients with early cervical cancer. Methods: Peripheral blood samples were obtained from 90 patients with early cervical cancer. CTCs were isolated and classified. The correlations of CTC counts and CTC phenotypes with clinicopathological features of patients were analyzed. Results: The positivity rate for CTCs in patients with stage I-IIA cervical cancer was 90%. An increased CTC number was observed in patients with FIGO stage II, pelvic lymph node metastasis, and lymphovascular involvement. There were 38.89% epithelial CTCs, 23.33% mesenchymal CTCs, and 14.44% mixed phenotypic CTCs, Mesenchymal CTCs were more common in patients with FIGO stage II, pelvic lymph node metastasis, lymphovascular involvement, and deep stromal invasion. Conclusion: CTCs with mesenchymal phenotypes are closely related to pelvic lymph node metastasis and lymphatic vascular invasion in stage I-IIA cervical cancer. Detection of circulating tumor cell phenotypes is helpful for the early diagnosis of cervical cancer micro-metastasis and for the assessment of disease status.

ObjectiveLaparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy.MethodsBetween August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charité Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator.ResultsA total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2–86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1–288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery.ConclusionThe combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials.

Background Regional nodal recurrence (RNR) in patients diagnosed with papillary thyroid carcinoma (PTC) has increased. Variable immunohistochemical (IHC) markers have been studied for predicting the likelihood of PTC for recurrence. We aimed to clarify the IHC expression of p53, Ecadherin and BRAF as potential markers of RNR in PTC. Method 145 (73 study group and 72 control group) patients with PTC were analyzed retrospectively between January 2010 and June 2017. Further classification to a specific histological variant was done, and IHC expression of p53, Ecadherin and BRAF was analyzed both in the primary tumor and in nodal recurrence. Results Regarding the risk of RNR, we found certain clinicopathologic features as elder age ≥55 years, tumor size >1 cm, presence of microscopic extrathyroid extension, presence of lymphovascular emboli, and conventional papillary subtype. Furthermore, IHC results for negative E-cadherin, and positive P53 and BRAF are significant risk factors, while radioactive iodine (RAI) adjuvant therapy decrease recurrence risk. Conclusion We found several risk factors for RNR in PTC diagnosed patients, all of which are easily achievable in clinical settings. In this regard, we suggested that patients with specific clinicopathologic and immunohistochemical features have strict follow up for early detection of RNR as it has a great impact on their survival.

The role of tumour thickness (TT), depth of invasion (DOI) from two different reference points (TT2 and TT3), perineural invasion (PNI) and lymphovascular invasion (LVI) were evaluated to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC). Reference points for measuring the DOI were suggested. Paraffin-embedded tissues of excisional biopsy cases diagnosed as OSCC were sectioned and stained in haematoxylin and eosin to study variables like TT1, TT2, TT3, PNI and LVI. Out of total 150 cases collected for the study, 136, 123 and 149 cases were qualified for analysis of TT1, TT2 and TT3 respectively. The association with LNM was studied using chi square test of independence. A binary logistic regression model (BLC) was developed to indicate high-risk cases. Receiver operating curve analysis suggested an optimum cut-off value. A significant correlation of TT1 (> 8.64, RR = 1.642, p = 0.018) and TT2 (> 7.64, RR = 2.041, p = 0.016), PNI (p = 0.028) and LVI (p = 0.000) were found with LNM. A mathematical model was suggested as Z = − 1.866 + 0.101TT2 + 2.106VI + e, where Z = log [(p/(1 − p)] p = probability of the case experiencing the event of interest. With the suggestion of a standardised reference point to measure DOI for the first time, this study has shown an association of TT1, TT2, PNI and LVI with LNM in Indian Population. The mathematical model can help in identifying high-risk cases in OSCC. Such studies would offer avenues for the pre-surgery assessment of depth of invasion and tumour thickness before performing neck dissection, thereby decreasing morbidity.

Background: Papillary thyroid microcarcinoma (Pm) is defined as a papillary carcinoma with size ≤ 10mm. On clinical and histological grounds, there are two presentations-‘incidental’ and ‘non-incidental’. Histopathological parameters like intratumoral/peritumoral fibrosis, multifocality, infiltrative borders, subcapsular location, lymphovascular emboli and histological type have been introduced in the reporting of Pm, besides the size which is considered an important prognostic/risk factor. Methods: The present study is a 5-year retrospective comparative study between the Pm which were incidentally detected, and those which had been previously diagnosed on fine needle aspiration/radiology or clinically suspicious of Pm. Result: The number of cases in both incidental (111) and non-incidental (110) Pm have been found to be comparable in the present study, which is attributable to meticulous grossing and extensive sampling of all thyroidectomy specimen. Size and multifocality has been significantly different between incidental and non-incidental Pm (p-value 5mm) of non-incidental Pm (p-value 0.05). In the incidental Pm of size ≤ 5mm, a good proportion of cases show these parameters, implicating their importance for further follow-up. Conclusion: Size and focality has been found to differ between incidental and non-incidental Pm. The histological parameters defined for Pm need to be followed up for a longer period to identify the prognostic significance, and their role in the different manifestation of incidental and non-incidental Pm.

Background and objectives To evaluate the effect of the varied histological subtypes on clinical outcomes and to determine the prognostic implications of mucinous adenocarcinomas (MAC) and signet ring cell carcinomas (SRCC) compared with classic adenocarcinomas (AC). Methods A total of 8005 patients, including 7502 AC, 428 MAC and 75 SRCC, who underwent definitive surgery between 2007 and 2015 at Fudan University Shanghai Cancer Center were remained for analysis in this study. Results MAC and SRCC were more common in right‐sided colon cancer, in males and in young patients, compared to AC; moreover, MAC and SRCC led to a higher probability to develop lymph node metastasis, lymphovascular invasion and perineural invasion. For survival outcomes, we found that the 5‐year overall survival (OS) of SRCC was significantly lower than that of MAC and AC, while the 5‐year OS of MAC is much lower than that of AC. However, in multivariable analysis, the difference in survival between SRCC, MAC and AC was no longer significant, especially when stratified by N stage. Conclusions MAC and SRCC are rare subtypes of colorectal cancer with a higher T stage, N stage as well as higher incidence of lymphovascular and nerve invasion. However, neither MAC nor SRCC was an independent predictor of decreased survival in multivariate analysis.

Oral cancers are the most common malignancy affecting Indian population with buccal mucosa being the frequent subsite. This study is to evaluate the histopathological factors influencing locoregional recurrence (LRR) and disease-free survival (DFS) in buccal mucosal squamous cell carcinoma (BSCC). One hundred and twenty patients treated surgically for BSCC with a curative intend between January 2014 and December 2015 were retrospectively analyzed. Histopathological factors like tumor stage, grade of differentiation, tumor front, skin involvement, bone involvement, depth of invasion, perineural invasion, lymphovascular emboli, primary resection margin in frozen section, nodal stage, extracapsular extension, and lymph node ratio were analyzed and compared for LRR and DFS. With a median follow-up of 41 months, LRR occurred in 34 patients (28.3%) and a 2-year DFS was 75.8%. Multivariate analysis identified that the factors that independently influenced the LRR were pathological nodal stage (p

Disputes exist regarding whether the apparent diffusion coefficient (ADC) can differentiate the tumor grade, deep myometrial invasion and lymphovascular space invasion (LVSI) in endometrial cancer. The aim of this review was to assess the diagnostic performance of the ADC value in endometrial cancer.The PubMed, Web of Science, Embase and Cochrane Library databases were searched for studies that used the ADC value to assess tumor grade, deep myometrial invasion and LVSI in endometrial cancer. We used forest plots to analyze the heterogeneity and generate the pooled sensitivity (SEN) and specificity (SPE). We used summary receiver operating characteristic (SROC) curves to work out the area under the SROC curve (AUC). Likelihood ratios (LRs) were also obtained.Of the 460 identified studies, 11 studies met our inclusion criteria and were included. Overall, nine studies (491 patients) aimed at differentiating high tumor grade had a pooled SEN, SPE and AUC of 77%, 73% and 81%, respectively; three studies (181 patients) for differentiating deep myometrial invasion had a pooled SEN, SPE and AUC of 71%, 67% and 77%, respectively; and two studies (106 patients) for differentiating LVSI had a pooled SEN and SPE of 66% and 74%, respectively. The positive and negative LRs were 2.77 and 0.35 for the tumor grade, 2.08 and 0.45 for deep myometrial invasion, and 2.48 and 0.45 for LVSI.This meta-analysis showed that the ADC value had a moderate diagnostic performance for the tumor grade, deep myometrial invasion and LVSI in endometrial cancer.

Lymphovascular invasion (LVI) of testicular germ cell tumors (GCT) is an important stage-determining variable in the evaluation of radical orchiectomy specimens. ERG endothelial cell expression, as detected by immunohistochemistry (IHC), robustly highlights lymphovascular spaces, and thus, we sought to assess the utility of ERG IHC for evaluation of GCT LVI. Hematoxylin and eosin (HE) slides from a retrospective cohort of 25 GCT radical orchiectomy specimens (emanating from a parent cohort of 159 radical orchiectomy GCT cases identified between 2003 and 2013) were reviewed, and sections with foci of positive or equivocal LVI were identified. ERG IHC was performed on sections off the surface of corresponding paraffin tissue blocks. All foci were then rescored as positive, equivocal, or negative for LVI based on ERG endothelial cell expression. Twenty-three and 13 foci were positive or equivocal for LVI by HE staining, respectively. Among the HE positive LVI foci, 20 (87%) were ERG IHC positive, whereas of the HE equivocal LVI foci, 5 (38%) were ERG IHC positive, 3 (23%) were ERG IHC negative, and 2 (15%) were ERG IHC equivocal; all other foci were lost for evaluation. Overall, ERG IHC helped resolve the LVI status of 61% of foci deemed equivocal for LVI by HE staining only. Although ERG IHC is useful in confirming definitive LVI status in a subset of GCT cases, the overall clinical impact of ERG IHC is limited for HE equivocal LVI foci in this specific retrospective patient cohort. Overall, in carefully selected clinical scenarios, these data suggest a supportive role for ERG IHC in evaluation of GCT LVI in radical orchiectomy specimens.

To investigate the prognostic significance of lymphovascular space invasion (LVI) and perineural invasion (PNI) in rectal cancer.Clinical data of 1,232 stage II-III rectal cancer patients from six tertiary institutions were analyzed. All patients were treated by long-course preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Adjuvant systemic chemotherapy was performed for 962 (78.1%) patients according to the multidisciplinary team's decision. Treatment outcomes and prognostic factors were evaluated according to the lymphovascular invasion (LVI) and perineural invasion (PNI) status.Five-year overall survival (OS) and recurrence-free survival (RFS) rates of the entire cohort were 84.1% and 71.1%, respectively. There is a significant difference in 5-year OS among both-absent, LVI+ only, PNI+ only, and both-present groups (89.1% vs. 77.9% vs. 67.6% vs. 56.2%; p 0.001). RFS at five years was significantly different among both-absent, LVI+ only, PNI+ only, and both-present groups (78.7% vs. 58.7% vs. 44.6% vs. 38.6%; p 0.001). The 5-year distant failure-free survival (DFFS) rate was also significantly different among four groups (84.6% vs. 61.4% vs. 54.2% vs 48.6%; p 0.001). Although adjuvant chemotherapy did not affect 5-year DFFS in the entire cohort, adjuvant chemotherapy significantly reduced the distant failure rate in patients with PNI+ patients (44.9% vs. 54.6%, p = 0.048), not LVI+ patients (65.0% vs. 56.1%, p = 0.487).Compared to LVI, PNI is a more significant prognostic factor in stage II-III rectal patients treated by preoperative CRT and TME surgery. The status of PNI rather than LVI could be an indicator for identifying patients who could benefit from adjuvant systemic chemotherapy.

Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix. As shown in the original Japanese group description, in recent studies, GAS represents a more aggressive disease than the usual-type endocervical adenocarcinoma (UEA). Detailed clinicopathological features of this variant remain to be elucidated in a larger series of patients.Patients were enrolled by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group after receiving the approval of each Institutional Review Board. The study population comprised of women with stage I to II endocervical adenocarcinomas who underwent surgery between 2000 and 2009. Representative slides were evaluated by central pathological review (CPR), categorized into either GAS or UEA, and correlated with clinicopathological features and outcome.Among the 393 enrolled patients with endocervical adenocarcinoma, 328 patients met the criteria for CPR and the study eligibility criteria and were included in further analysis. A total of 95 of the 328 tumors were classified as GAS. Compared with UEA, GAS was more significantly associated with bulky mass, deep stromal invasion, lymphovascular space invasion, parametrial invasion, ovarian metastasis, positive ascitic fluid cytology, pelvic lymph node metastasis, and pathological (p) T stage but was not related to the degree of histological differentiation. Disease-free survival (P 0.0001) and overall survival (P 0.0001) were poorer in patients with GAS than in those with UEA.GAS showed aggressive behavior with ominous histopathological predictors as well as decreased survival. GAS is therefore considered a distinct entity that should be distinguished from UEA.UMIN Clinical Trials Registry: UMIN000007987.

BACKGROUND The aim of this study was to assess the presence of HPV DNA in cervical tissues and lymph nodes in patients who have uterine cervical neoplasms with lymphatic metastases and who underwent surgery for invasive cervical cancer and pelvic lymphadenectomy, to establish the utility of HPV type and viral load in predicting disease progression. MATERIAL AND METHODS We retrospectively assessed 88 patients with uterine cervical neoplasms with lymph node metastases. All 88 patients were in FIGO stage IA-IIB. A total of 316 paraffin-embedded archival tissues (88 cervical samples and 228 pelvic lymph node specimens) were acquired. All the samples were analyzed using real-time PCR to determine HPV DNA presence/type and to quantify viral load. RESULTS In total, 17 HPV genotypes were detected in the cervical lesions and pelvic lymph nodes of the patients. The most common HPV type in all samples was HPV16, followed by HPV18. The existence of HPV16 DNA and low HPV16 viral load in cervical lesions were also significantly associated with disease recurrence. Furthermore, lymphovascular space involvement was also correlated with worse disease outcome. CONCLUSIONS HPV16 DNA presence and low viral load in primary lesions can be used to predict disease recurrence. HPV DNA is a favorable prognostic indicator in patients with uterine cervical neoplasms who have lymphatic metastases.

Objective: The aim of this study was to investigate the clinicopathological features and survival of patients with undifferentiated endometrial carcinoma (UEC). Methods: Patients who were operated between 2006 and 2014 for endometrial cancer (EC) in the same center were retrospectively reviewed from the clinical archive. Data were obtained from patient files. Survival curves and rates were calculated using the Kaplan-Meier method, and differences in survival were evaluated using the Log-Rank test. Results: In this study, 774 patients with EC were screened. According to the pathology report, 14 (1.8%) had undifferentiated type histology. The mean age, parity and body mass index (BMI) of the patients were 58.6 year (range 40-73); 3.28 (range 0-6) and 32.1 kg/m2 (range 22.8-41.7), respectively. Of the patients, 64% (n=9) had deep myometrial invasion, 93% (n=13) had lymphovascular space invasion, and 57% (n=8) had cervical involvement. Tumor size was greater than 5 cm in 64% (n=9) of the patients. Thirty five percent (n=5) of the patients were stage 1A, 21% (n=3) were stage 1B, 14% (n=2) were stage 2, 14% were stage 3C, and 14% were stage 4. As adjuvant therapy, 21% (n=3) of the patients received chemotherapy only, 14% (n=2) received radiotherapy only, and 57% (n=8) received chemotherapy and radiotherapy together. The mean follow-up duration was 36 months (range 4-104). In this period, survival rates were 77% for early-stage (FIGO 1-2) and 0% for advanced-stage (FIGO 3-4). The mean survival duration was 81 months in the early stage; 6.8 months in advanced stage (Log Rank test P value= 0.001). Conclusion: According to this study, UEC is highly associated with pathological poor prognostic factors such as deep myometrial invasion, lymphovascular space invasion, cervical involvement and large tumor size. Patients with advanced stage do not have the chance to survive. Long-term survival is possible if the diagnosis and treatment of the disease is achieved while the tumor is limited to the uterus.

Objectives A sea of literature addressing the adequacy of mucosal/soft tissue surgical margins in oral cavity cancers is available, but no mention exists regarding bony margins. We aim to study the predictors and impact on survival of positive bony margins and propose a safe margin distance. Methods This is a retrospective study of 400 consecutive surgically treated pT4 oral cavity squamous cell carcinoma patients between January 2012 and December 2015. The factors predicting positive bony margins were determined using chi-square test. Kaplan Meier and Cox regression hazard models were used for survival analysis. The median follow up was 36 months. Results The only factor that significantly predicted positive bony margins was lymphovascular emboli. The 3-year OS with bony margin positivity was 36.9%, compared to 67.5% for patients with adequate margins. When the tumor infiltrated the bone beyond mucosa (20.25%) the survival outcomes were significantly worse than the other patterns. Microscopic spread was seen in 10% cases, at a distance of 8 mm, the presence of which significantly impacted survival outcomes. Analysis of the receiver operating curve identified a cutoff of more than 15 mm as appropriate for classifying adequate bony margins. When the margins were taken above this, a significant positive impact on survival outcomes was present. Conclusion The presence of lymphovascular emboli may impact the status of bony margins. Based on our results, to achieve an “adequate margin in bone” we propose taking the bony cut at least 15 mm away from the clinically discernible tumor when treating advanced oral cancers.

This study aimed to evaluate the prognostic significance of lymphovascular (LVI), perineural invasion (PNI), and tumor budding positivity in patients with colorectal cancer. From January 2008 to December 2011, 3707 consecutive patients who underwent curative surgery for stage I–III colorectal cancer were assessed. These patients were then categorized into four groups based on LVI, PNI, and tumor budding (risk grouping): all negative (n = 1495), 1 + only (n = 1063), 2 + only (n = 861), and all positive (n = 288). With a median follow-up period of 52 months, the 5-year disease-free survival rates of the risk groups were significantly different in terms of cancer staging (stage I, Stage II, and Stage III: P = 0.006, P

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.

Objective Lymphovascular infiltration (LVI) is frequently detected in gastric cancer (GC) specimens. Studies have revealed that GC patients with LVI have a poorer prognosis than those without LVI. Methods In total, 1,007 patients with curatively resected GC at Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital were retrospectively enrolled. The patients were categorized into two groups based on the LVI status: a positive group (PG; presence of LVI) and a negative group (NG; absence of LVI). The clinicopathological factors corrected with LVI and prognostic variables were analyzed. Additionally, a pathological lymphovascular-node (lvN) classification system was proposed to evaluate the superiority of its prognostic prediction of GC patients compared with that of the eighth edition of the N staging system. Results Two hundred twenty-four patients (22.2%) had LVI. The depth of invasion and lymph node metastasis were independently associated with the presence of LVI. GC patients with LVI demonstrated a significantly lower overall survival (OS) rate than those without LVI (42.8% vs. 68.9%, respectively; P

To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI).A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information. Variables were compared between patients with PNI to those without PNI.Of the 421 patients included in the study, 32 (7.6%) had tumors with PNI. There were no significant differences in age, race/ethnicity, smoking history, histologic subtype, or grade between the group of patients with PNI and the group without PNI. The group with PNI was more likely to have lichen sclerosus (25.0% vs. 15.4%, p = 0.024), stage III/IV disease (59.4% vs. 36.0%, p = 0.007), lymph node involvement (50.0% vs. 21.6%, p = 0.002), and lymphovascular space invasion (LVSI) (53.1% vs. 15.9%, p 0.001). A higher proportion of patients in the PNI group underwent primary or adjuvant radiation therapy (68.8% vs. 45.0%, p = 0.016). The median follow-up was 67.1 months (range 1.0 to 284.3). Patients with PNI had significantly shorter overall survival (OS), median 25.5 vs. 94.3 months (p 0.001), and progression-free survival (PFS), median 17.5 vs. 29.0 months (p = 0.004). After adjusting for stage, patients with PNI had a greater risk for death and progression (OS: hazard ratio, 2.71; p 0.001; PFS: hazard ratio, 1.64; p-value = 0.020).PNI should be considered an independent poor prognostic factor for patients with vulvar carcinoma, and should be included as part of the pathologic analysis.

Background/Aims: The importance of adjuvant radiotherapy in patients with close margin resections for mucoepidermoid carcinoma of the parotid gland remains unclear. Methods: Patients who underwent parotidectomy for mucoepidermoid carcinoma with or without adjuvant radiotherapy at a single academic tertiary care center from 2000 to 2014 were identified. Included patients had negative but close (≤2 mm) surgical margins without other high-risk histopathological factors including advanced T-stage, positive nodal disease, lymphovascular or perineural invasion, or high-grade histology. Results: Nineteen patients were identified, of whom 15 (79%) were observed postoperatively, while 4 (21%) underwent adjuvant radiotherapy. There were no significant differences in extent of parotidectomy, elective neck dissection, T staging, or tumor size between patients who were observed and those undergoing adjuvant radiation. There were no locoregional or distant recurrences in any patients at a mean follow up 74.3 months. Patients undergoing adjuvant radiation, however, had significantly more intermediate-grade as compared to low-grade histology (75% vs. 13%, difference 62%, 95% CI 4% to 100%). Conclusions: Patients with negative but close (≤2 mm) surgical margins without other high-risk histopathological factors have excellent long-term locoregional control with surgery alone. The effects of adjuvant radiotherapy for those who have intermediate-grade disease remain uncertain.

Although the majority of papillary thyroid cancers (PTC) are indolent, a subset of PTCs behaves aggressively due to extensive invasion and distant metastasis. Integrin β4, a member of the integrin family, has been shown to enhance the progression in some malignancies; however, its role in PTC remains unclear. Here, we demonstrated that β4 overexpression was associated with extrathyroid extension, lymph node metastasis, high TNM stage, and poor overall survival based on The Cancer Genome Atlas cohort. Immunohistochemistry showed that β4 expression was significantly upregulated in the tumors with infiltrating growth pattern, as well as those with positive lymphovascular invasion. Moreover, β4 was invariably overexpressed in the lymphovascular tumor thrombi, which has not been reported before. After shRNA-induced knockdown of β4 in vitro, the migration, invasion and scratch repair ability of the tumor cells were significantly reduced. Furthermore, β4 reduction decreased anchorage-independent growth and increased anoikis. The bioinformatics analysis revealed that approximately 70 pathways were significantly dysregulated in the high β4 expression group. The MAPK pathway and propanoate metabolism were located in the network center of those pathways. Taken together, our results suggest that β4 could promote the tumor's aggressiveness by enhancing invasion and antagonizing anoikis. The upregulated expression of β4 in the tumor thrombi is intrinsically linked to its role in strengthening the anoikis resistance.

ObjectiveThe necessity of lymphadenectomy and the prediction of lymph node involvement (LNI) in endometrial cancer (EC) have been hotly-debated questions in recent years. Machine learning is a broad field that can produce results and estimations. In this study we constructed prediction models for EC patients using the Naïve Bayes machine learning algorithm for LNI prediction.MethodsThe study assessed 762 patients with EC. Algorithm models were based on the following histopathological factors: V1: final histology; V2: presence of lymphovascular space invasion (LVSI); V3: grade; V4: tumor diameter; V5: depth of myometrial invasion (MI); V6: cervical glandular stromal invasion (CGSI); V7: tubal or ovarian involvement; and V8: pelvic LNI. Logistic regression analysis was also used to evaluate the independent factors affecting LNI.ResultsThe mean age of patients was 59.1 years. LNI was detected in 102 (13.4%) patients. Para-aortic LNI (PaLNI) was detected in 54 (7.1%) patients, of which four patients had isolated PaLNI. The accuracy rate of the algorithm models was found to be between 84.2% and 88.9% and 85.0% and 97.6% for LNI and PaLNI, respectively. In multivariate analysis, the histologic type, LVSI, depth of MI, and CGSI were independently and significantly associated with LNI (pConclusionsMachine learning may have a place in the decision tree for the management of EC. This is a preliminary report about the use of a new statistical technique. Larger studies with the addition of sentinel lymph node status, laboratory findings, or imaging results with machine learning algorithms may herald a new era in the management of EC.

Objective: Both performances of lymphadenectomy and benefit of adding adjuvant radiotherapy are controversial for patients with International Federation of Gynecology and Obstetrics stage IB endometrioid type endometrial cancer. We aimed to identify the role of lymphadenectomy and adjuvant radiation therapy as well as clinicopathological prognostic factors for this group of patients.Study Design: Records of all patients (n=132) with stage IB endometrioid endometrial cancer who were referred to or treated in our institution between Jan 1992 and Dec 2013 were retrospectively reviewed. Cox Proportional Hazard Regression Analysis was used to determine the effects of lymphadenectomy and adjuvant radiation as well as other clinicopathological factors on disease free survival and overall survival.Results: Mean age was 59.9 years (range, 45-82). Lymphadenectomy didn't perform in 36 (27.3%) patients and 23 (17.4%) patients did not have any kind of adjuvant treatment. Mean lymph node count was 18.8 (range, 3-67). Federation of Gynecology and Obstetrics grade, lymphovascular space invasion, lymphadenectomy, receiving adjuvant treatment and type of received adjuvant therapy were not associated with disease free survival and overall survival for the entire cohort. In a subgroup of patients with grade1&2 tumor, 5-year disease free survival rates were 80% and 50% (p=0.4), respectively and overall survival rates were 94.8% and 93.8% (p=0.2), respectively for patients who had or didn't have adjuvant radiotherapy. While performance of lymphadenectomy was not significantly associated with disease free survival in this subgroup (p=0.56), this association was statistically significant for overall survival (97.9% vs. 86.4%, p=0.04) Conclusion: Benefit of adjuvant radiotherapy in regard to prevention of recurrence needs to be confirmed by further studies. Lymphadenectomy had a survival benefit for patients with myometrial invasion greater than a half of myometrial thickness.

Objectives Rete testis invasion by germ cell tumors is frequently concomitant with lymphovascular or spermatic cord invasion (LVI/SCI); independent implications for staging are uncertain. Methods In total, 171 seminomas and 178 nonseminomatous germ cell tumors (NSGCTs; 46 had 1%-60% seminoma component) came from five institutions. Metastatic status at presentation, as a proxy for severity, was available for all; relapse data were unavailable for 152. Rete direct invasion (ReteD) and rete pagetoid spread (ReteP) were assessed. Results ReteP and ReteD were more frequent in seminoma than NSGCT. In seminoma, tumor size bifurcated at 3 cm or more or less than 3 cm predicted metastatic status. Tumors with ReteP or ReteD did not differ in size from those without invasions but were less than with LVI/SCI; metastatic status or relapse did not show differences. In NSGCT, ReteP/ReteD did not correlate with size, metastatic status, or relapse. Conclusions Findings support retaining American Joint Committee for Cancer pathologic T1 stage designation for rete testis invasion and pT1a/pT1b substaging of seminoma.

Objective To investigate the prevalence of lymph nodes and lymph node metastases (LNMs) in the upper paracervical lymphovascular tissue (UPLT) in early stage cervical cancer. Methods In this prospective study consecutive women with stage IA1-IB1 cervical cancer underwent a pelvic lymphadenectomy including identification of sentinel nodes (SLNs) as part of a nodal staging procedure in conjunction with a robotic radical hysterectomy (RRH) or robotic radical trachelectomy (RRT). Indocyanine green (ICG) was used as tracer. The UPLT was separately removed and defined as “SLN-parametrium” and, as all SLN tissue, subjected to ultrastaging and immunohistochemistry. Primary endpoint was prevalence of lymph nodes and metastatic lymph nodes in the UPLT. Secondary endpoints were complications associated with removal of the UPLT. Results One hundred and forty-five women were analysed. Nineteen (13.1%) had pelvic LNMs, all identified by at least one metastatic SLN. In 76 women (52.4%) at least one UPLT lymph node was identified. Metastatic UPLT lymph nodes were identified in six women of which in three women (2.1% of all women and 15.8% of node positive women) without lateral pelvic LNMs. Thirteen women had lateral pelvic SLN LNMs with either no (n = 5) or benign (n = 8) UPLT lymph nodes. No intraoperative complications occurred due to the removal of the UPLT. Conclusion Removal of the UPLT should be an integral part of the SLN concept in early stage cervical cancer.

Simple Summary Sentinel lymph node (SLN) status is still the most important prognostic factor for melanoma patients; however, the efficacy of completing lymph node dissection remains questionable. The aim of our study was to assess the correlation between known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, and SLN status. Statistical analysis revealed that Breslow thickness was associated with SLN status; however, neither NRAS nor BRAF showed a predictive value. Furthermore, NRAS mutation in primary tumors proved to be an independent factor of tumor progression. This suggests that regardless of the SLN status, the NRAS-mutant subgroup of patients requires closer monitoring. Abstract Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, as well as disease outcome. Methods: Our retrospective single-center study involved 159 melanoma cases, who underwent SLN biopsy. The following clinico-pathological data were collected: age, gender, location of primary tumor, Breslow thickness, ulceration degree, histological subtype, mitosis count, lymphovascular and perineural invasion, presence of tumor-infiltrating lymphocytes, regression signs, mutations of BRAF and NRAS of the primary tumors, and SLN status. Results: From the studied clinico-pathological factors, only Breslow thickness increased the risk of SLN positivity (p = 0.025) by multivariate analysis, while neither BRAF nor NRAS mutation of the primary tumor proved to be a predictor of the SLN status. While the NRAS-mutant subgroup showed the most unfavorable outcome for progression-free and distant metastasis-free survival, their rate of positive SLNs proved to be relatively lower than that of patient groups with BRAF mutation and double-wild-type phenotypes. Conclusion: Similarly to the importance of SLN positivity, NRAS mutation of the primary tumor proved to be an independent prognostic factor of progression. Therefore, despite negative SLN, this NRAS-mutant subgroup of patients still requires closer monitoring to detect disease progression.

Context.—Primary tumor stage (pT) is an important prognostic indicator in colonic adenocarcinomas; however, cases that have no muscle fibers beyond the advancing tumor edge but also show no extension beyond the apparent outer border of the muscularis propria (termed pT2int) have not been previously studied.Objective.—To address the clinicopathologic characteristics and prognosis of pT2int tumors.Design.—We recharacterized 168 colon carcinomas and compared pT2int cases to bona fide pT2 and pT3 tumors.Results.—In side-by-side analysis, 21 pT2int cases diverged from 29 pT2 tumors only in terms of larger size (P = .03), but they were less likely to show high-grade (P = .03), lymphovascular (P < .001), and extramural venous invasion (P = .04); discontinuous tumor deposits (P = .02); lymph node involvement (P = .001); and advanced stage (P = .001) compared with 118 pT3 tumors. Combining pT2int with pT2 cases (versus pT3) was a better independent predictor of negative lymph nodes in multivariate analysis (P = .04; odds ratio [OR], 3.96; CI, 1.09–14.42) and absent distant metastasis in univariate analysis (P = .04) compared with sorting pT2int with pT3 cases (versus pT2). Proportional hazards regression showed that pT2 and pT2int cases together were associated with better disease-free survival compared with pT3 tumors (P = .04; OR, 3.65; CI, 1.05–12.70). Kaplan-Meier analysis demonstrated that when pT2int were grouped with pT2 tumors, they were significantly less likely to show disease progression compared with pT3 (P = .002; log-rank test) and showed a trend toward better disease-specific survival (P = .06) during a mean patient follow-up of 44.9 months.Conclusions.—These data support the conclusion that pT2int carcinomas have clinicopathologic characteristics and are associated with patient outcomes more closely aligned with pT2 rather than pT3 tumors.

The 2018 publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial changed the surgical paradigm for women with early-stage cervical cancer. The study randomized 631 women with stage IA1 (with lymphovascular space invasion), IA2, and IB1 cervical cancer to minimally invasive or

Lymphangiomas are classified as lymphatic malformations, which are more common in children and rare in adults. It frequently occurs in the cervical and axillary regions and uncommonly in the retroperitoneum. A 39-year-old woman presented to our department for the investigation for a 55 mm asymptomatic mass in the right anterior adrenal cavity. Abdominal ultrasound showed a tumor containing cysts in the right anterior adrenal cavity. Contrast-enhanced computed tomography showed that the tumor was poorly contrasted and ill-defined. Magnetic resonance imaging suggested that the tumor contained a small amount of fat. The tumor tended to grow, and the possibility of malignant diseases such as liposarcoma could not be excluded. Therefore, surgical resection was performed. Since intraoperative findings showed that the tumor tightly invaded to the duodenum and pancreatic head, a pancreaticoduodenectomy was selected. The entire tumor was removed without exposing the tumor. Macroscopic findings indicated that the specimen was 55 mm in size, indistinctly demarcated, yellow–white in color, and polycystic. Histologically, lymphovascular proliferation was observed with infiltration of the pancreatic head and the duodenal muscle layer. The diagnosis of lymphangioma was finally made. There was no recurrence 2 years after surgery.

Clinicopathologic risk factors previously were a guide to the indication for adjuvant treatment in early-stage endometrial cancer until the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines introduced