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Made available in DSpace on 2022-04-29T08:36:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-02-01 Objective: The objective of this study was to investigate the association between survival rate and lymphovascular invasion (LVI) and perineural invasion (PNI) in the tumor invasive front (TIF) of squamous cell carcinoma of the tongue (TSCC). Study Design: Seventy patients with TSCC were included. The retrospective analysis included demographic, clinical, and histopathologic data. Tissue blocks containing the TIF were stained with anti-α-smooth muscle actin and anti-S100 to detect LVI and PNI, respectively. Overall survival (OS) and disease-specific survival (DSS) were assessed using Pearson's chi-square test, Kaplan-Meier method, and Cox regression. Results: LVI and PNI were detected in 61.4% and 78.6% of the TSCC samples at the TIF, respectively. LVI and PNI were present in 54.3% of the cases and were associated with advanced clinical stage, lymph node resection, metastatic nodes, and lower survival (P < .05). The 5-year OS and DSS rates were 44% and 52%, respectively. Multivariate analysis showed that primary tumors >3.0 cm (hazard ratio = 4.29; P = .004) and a concomitant presence of LVI and PNI at the TIF (hazard ratio = 4.0; P = .012) were independent predictors for worse DSS. Conclusion: LVI and PNI, identified by immunostaining at the TIF, are potential prognostic markers of TSCC. School of Dentistry São Paulo State University (UNESP) Basic and Clinical Dentistry Group School of Dentistry CES University Basic Sciences Group School of Medicine CES University School of Medicine CES University Pathology Laboratory Las Américas School of Dentistry University of Antioquia Department of Physiology and Pathology School of Dentistry São Paulo State University (UNESP). Araraquara School of Dentistry São Paulo State University (UNESP) Department of Physiology and Pathology School of Dentistry São Paulo State University (UNESP). Araraquara

Introduction Although the molecular profile of the breast provides prognostic indicators, risk stratification in breast cancer continues to be a challenge. Therefore, it is mandatory to seek new prognostic markers that could aid the early diagnosis of potential metastases in biopsy samples from breast cancer; among these are increased Snail-1 and Claudin-4 expression. Objectives The aim of this study was to analyze the correlation between Snail-1 and Claudin-4 with other clinical-pathological parameters and distinct molecular subtypes. Methods This study included 110 patients with invasive ductal carcinoma from 2009 to January 2015. Snail-1 and Claudin-4 were assessed by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks and the data were correlated with clinical-pathological data and survival. Results A total of 65 patients (68.2%) were positive for Snail-1 and 85 patients (77.3%) were positive for Claudin-4. High Snail-1 and high Claudin-4 were detected in high-grade tumors and were associated with lymphovascular infiltration and lymph node metastases (p Conclusion High Snail-1 and Claudin-4 levels were associated with adverse outcomes in patients with breast cancer.

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.

Aims and methodsThe prognostic role of tumour budding (TBd) and its interaction with the stromal microenvironment has gained a lot of attention recently, but remains unexplored in gall bladder cancer (GBC). We aimed to study the interrelationship of TBd by International Tumour Budding Consensus Conference scoring system, tumour–stroma ratio (TSR) and desmoplastic stromal reaction (DSR) with the conventional clinicopathological prognostic factors, mortality and overall survival (OS) in 96 patients of operated GBC.ResultsHigher age, high TNM stage, lymphovascular and perineural invasion, positive resection margins, higher TBd score, low TSR and immature DSR were significantly associated with worse OS. However, on multivariate analysis, only metastases, positive resection margins and TSR ConclusionA high TBd, low TSR and immature DSR were significantly associated with several high-risk clinicopathological parameters and poor OS in GBC. These novel, simple, reproducible and cost-effective parameters may be included in the routine reporting checklist for GBC as additional prognostic parameters that can substratify the high-risk patients.

Background This study aims to formulate a risk classification system predicting the cancer-specific survival (CSS) for postoperative stage IB NSCLC patients without lymphovascular (LVI) and visceral pleural (VPI) invasion to guide treatment decision making and assist patient counseling. Method A total of 4,238 patients were included in this study. Patients were randomly divided into training and validation cohorts (7:3). The risk factors were identified by Cox regression. Concordance index (C-index), calibration curves, and Decision Curve Analyses (DCAs) were used to evaluate the performance of nomogram. We applied X-tile to calculate the optimal cut-off points and develop a risk classification system. The Kaplan-Meier method was conducted to evaluate CSS in different risk groups, and the significance was evaluated by log-rank test. Result Among the 4,238 patients, 1,014(23.9%) suffered cancer-specific death. In the training cohort, univariable and multivariable Cox regression analyses revealed that age, gender, pathological subtype, grade, tumor size, the number of removed lymph nodes and surgical type were significantly associated with CSS. According to these results, the nomogram was formulated. The C-index of the prediction model was 0.755 in the training cohort (95%CI: 0.733–0.777) and 0.726 (95%CI: 0.695–0.757) in the validation cohort. The calibration curves in training and validation cohort exhibited good agreement between the predictions and actual observations. The Decision Curve Analyses (DCAs) showed net benefit can be achieved for nomogram. A risk classification system was further constructed that could perfectly classify patients into three risk groups. Conclusion In this study, we constructed a nomogram to support individualized evaluation of CSS and a risk classification system to identify patients in the different risk groups in stage IB NSCLC patients without LVI and VPI. These tools could be useful in guiding treatment decision making and assisting patient counseling.

Introduction. BRCA1 dysfunction is a hallmark of both hereditary and sporadic breast cancer. BRCA1 protein expression can be lost by germline mutation, somatic mutation or promoter hypermethylation. This study aimed to explore BRCA1 dysfunction in breast cancer patients by immunohistochemistry and to study its association with prognostic factors. Material and methods. BRCA1 protein expression was assessed by immunohistochemistry on formalin fixed paraffin embedded tissue blocks of 110 invasive breast carcinoma patients. Furthermore, the clinical findings and tumor features associated with BRCA1 dysfunction were characterized. Results. Reduced BRCA1 immunoreactivity was observed in 19% of breast cancer cases. Although these patients presented with aggressive tumor characteristics, statistical significance was observed only with presence of lymphovascular emboli (p < 0.05). These results suggest that loss of BRCA1 protein expression is associated with an aggressive phenotype of breast carcinoma. Conclusions. Immunohistochemistry for BRCA1 protein expression in tumor tissues may provide a less expensive screening tool to identify BRCA1 dysfunction due to genetic or epigenetic alterations.

OBJECTIVE: This study aims to investigate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with epithelial ovarian cancer. STUDY DESIGN: Between January 2012 and December 2018, the data and preoperative levels of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio of 116 epithelial ovarian cancer patients were retrospectively collected. The association of these relevant markers with outcomes was analyzed. RESULTS: The difference was observed concerning optimal and suboptimal debulking in platelet-to-lymphocyte ratio ratios (p=0.04). Lymphovascular space involvement was significantly associated with higher platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio ratios (p2.45 (HR 0.714, CI 0.622-0.794, p179.4 (HR 0.736, CI 0.646-0.814, p2.45 had a sensitivity of 78.26% (95% CI: 56.3 to 92.5%) and a specificity of 54.84% (95%CI: 44.2 - 65.2) (p=0.03). CONCLUSION: The evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is important in obtaining prognostic information before surgery. However, no significant association between the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio with survival was identified.

Poorly cohesive carcinomas (PCCs) are neoplasms characterized by a dyshesive cell invasion pattern featuring single-cell or cord-like stromal infiltration. Although they have been extensively studied in the stomach and other digestive system organs, limited data regarding nonampullary small bowel poorly cohesive carcinomas (SB-PCCs) are hitherto available. The aims of our study were to analyze the clinicopathologic and immunophenotypical features of SB-PCCs (PCC pattern accounting for >50% of the neoplasm) and to compare them with small bowel adenocarcinomas (SBAs), not otherwise specified (SBAs-NOS) and with cancers with a histologically distinct PCC component accounting for 10% to 50% of the neoplasm (mixed-poorly-cohesive-glandular-SBAs). Fifteen SB-PCCs were identified and compared with 95 SBAs-NOS and 27 mixed-poorly-cohesive-glandular-SBAs. Most SB-PCCs (67%) were composed of

Evaluating nodal metastases in low-grade serous ovarian cancer (LGSOC) patients.Women with LGSOC who had undergone primary cytoreductive surgery comprising systematic pelvic-paraaortic lymphadenectomy were included. Data were obtained retrospectively from 12 oncology centers.One hundred and forty-eight women with LGSOC who had undergone comprehensive surgical staging were included. Seventy-one (48.0%) patients had metastatic lymph nodes. Preoperative serum CA-125 levels of ≥170 U/ml (odds ratio [OR]: 3.84; 95% confidence interval [CI]: 1.22-12.07; p = 0.021) and presence of lymphovascular space invasion (LVSI) (OR: 13.72; 95% CI: 3.36-55.93; p 0.001) were independent predictors of nodal metastasis in LGSOC. Sixty (40.5%) patients were classified to have apparently limited disease to the ovary/ovaries. Twenty (33.3%) of them were upstaged after surgical staging. Twelve (20.0%) had metastatic lymph nodes. Presence of LVSI (OR: 12.96; 95% CI: 1.14-146.43; p = 0.038) and preoperative serum CA-125 of ≥180 U/ml (OR: 7.19; 95% CI: 1.35-38.12; p = 0.02) were independent predictors of lymph node metastases in apparent Stage Ⅰ disease.Clinicians may consider to perform a reoperation comprising systematic lymphadenectomy in patients who had apparently limited disease to the ovary/ovaries and had not undergone lymphadenectomy initially. Reoperation may be considered particularly in patients whose preoperative serum CA-125 is ≥180 U/ml and/or whose pathological assessment reported the presence of LVSI.

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.

Yuncan Zhou, Weiping Wang, Ke Hu, Fuquan Zhang Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ke Hu; Fuquan Zhang Email huk@pumch.cn; zhangfuquan3@sina.comPurpose: No consensus has been reached regarding the survival difference between cervical adenocarcinoma (ADC) and adenosquamous carcinoma (ASC) patients. The purpose of this study was to compare survival outcomes and prognostic factors between early-stage ADC and ASC patients.Patients and Methods: We retrospectively reviewed stage IB-IIA patients with ADC and ASC who underwent radical hysterectomy and postoperative radiotherapy between June 2012 and December 2017.Results: A total of 125 patients were enrolled in our study (97 with ADC and 28 with ASC). The median follow-up period was 53.4 months. Compared with ASC patients, patients with ADC tended to have a higher proportion of positive pelvic lymph nodes (7.1% and 26.8%, respectively; p = 0.028). The most common site of distant metastasis was the lung, followed by the intestine and colon. The 5-year overall survival (OS), disease-free survival (DFS), pelvic control, and distant control rates for ADC and ASC patients were 83.6% and 92.0% (p = 0.349), 77.5% and 87.7% (p = 0.279), 81.8% and 96.2% (p = 0.121), and 88.3% and 87.7% (p = 0.948), respectively. Parametrial invasion was a prognostic factor for OS. Lymphovascular space involvement was a prognostic factor for DFS.Conclusion: ADC patients were more likely to have positive pelvic lymph nodes than those with ASC. There was no significant difference in survival outcomes between patients with ADC and ASC.Keywords: cervical adenocarcinoma, adenosquamous carcinoma, survival outcomes, parametrial invasion, lymphovascular space involvement

Aim To analyze the risk factors of lymph node involvement in pure endometrioid type endometrial cancer and assess factors that necessitate lymphadenectomy. Methods Patients who had been operated on due to endometrial cancer and whose final pathology was reported as pure endometrioid carcinoma between January 2014 and January 2020 were assessed. Hysterectomy, bilateral salpingo-oophorectomy, and systematic lymphadenectomy were performed in all patients. All specimens were reported by expert gynecopathologists. Results The lymph node positivity rate was 14.4%. When the study population was classified according to the Mayo risk criteria; lymph node involvement in the low-risk and high-risk groups was 9.1% and 14.8%, respectively and there was no statistically difference (p > 0.05). The median of tumor size and the rate of deep myometrial invasion, lymphovascular space invasion, adnexal involvement, FIGO grade 3 tumor were found significantly higher in the positive lymph node group in univariate analysis. In the receiver operating characteristic curve analysis, the cut-off value of the tumor diameter was determined as 47.5 mm (sensitivity 85%, specificity 62%). Every 10 mm increase in tumor diameter increased the risk of lymph node involvement 10 times. Conclusion This study defined that the tumor diameter is an independent predictor for lymphatic dissemination. In the future, it could be shown that even with new modeling based on tumor diameter, lymphadenectomy or adjuvant radiotherapy requirements would be reevaluated.

Pendahuluan: Kanker payudara seharusnya dapat ditemukan pada tahap yang lebih dini, akan tetapi kanker ini lebih sering diketahui pada stadium lanjut yang menyebabkan tingginya angka kematian. Prognosis kanker yang buruk akan mempengaruhi kualitas hidup pasien, kondisi keuangan, peran dan fungsi pasien dan keluarga bahkan kematian. Acuan prognosis pada pasien kanker payudara didasarkan pada analisa penanda biologis tumor primer yang mencakup reseptor estrogen (ER), reseptor progesteron (PR), Human Epidermal Growth Factor Receptor 2 (HER2) dan Ki67 yang diklasidikasikan menjadi 4 subtipe molekuler yaitu Luminal A, Luminal B, HER2 overexpression, dan Triple Negative. Metode: Jenis penelitian ini menggunakan metode studi systematic review dengan data yang akan digunakan adalah hasil-hasil penelitian yang telah beredar di dunia. Populasi penelitian ini adalah literatur jurnal hasil pencarian mengenai infiltrasi limfovaskular terhadap subtipe molekuler dari kanker payudara yang dipublikasikan di jurnal internasional dan dapat diakses melalui internet. Sampel penelitian ini ditentukan berdasarkan beberapa kriteria inklusi dan eksklusi yang telah dibuat. Hasil: Dari 5 jurnal internasional yang telah dikumpulkan, selanjutnya dianalisis menggunakan forest plot. Berdasarkan analisis data, didapatkan P =0,21 yang artinya uji perbedaan subkelompok menunjukkan bahwa tidak ada efek subkelompok yang signifikan terjadi secara statistik. Simpulan: Tidak terdapat hubungan antara infiltrasi limfovaskular dengan subtipe molekuler kanker payudara invasif.

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.

Summary Accurate staging of endometrial carcinoma is crucial to optimize patients’ care. A pivotal parameter that pathologists evaluate to guide staging is the presence of cervical stromal involvement. However, the standard protocol for adequate sampling of the cervix is lacking. A total of 71 grossly unremarkable cervices in hysterectomy specimens with endometrial carcinomas have been studied. Sixty-three (89.7%), five (7.0%), and three (4.2%) were FIGO stage I, II, and III, respectively. Of 71 (8.5%) cases, 6 cases had cervical stromal involvement, among which, 4 (67%) showed endometrioid carcinoma (EC), 1 case of serous carcinoma, and 1 carcinosarcoma. Microcystic elongated and fragmented (MELF) pattern was identified in 12 (16.9%) cases, among which 11 were EC. The presence of MELF pattern was associated with advanced age, deeper myometrial invasion, and advanced FIGO stage. Tumors with lower uterine segment involvement (5/6; 80%), lymphovascular space invasion (4/6; 67%), and MELF pattern (3/6; 50.0%) tended to have cervical stromal involvement. Thus, we provide evidence that the presence of these features in hysterectomy specimens from patients with endometrial carcinoma may warrant extended sampling of the cervix while submitting four representative sections (one section from each quadrant) seems adequate to evaluate for occult cervical stromal involvement in grossly unremarkable cervices in the absence of these features.

The presence of lymphovascular space invasion (LVSI) is not yet included in international recommendations neither as a prognostic factor nor as a parameter for the decision to use adjuvant chemotherapy in FIGO stage I/IIa ovarian cancer (OC).This study set out to evaluate the impact of LVSI on Overall Survival (OS) and Recurrence-Free Survival (RFS) in patients managed for epithelial OC.Retrospective multicenter study by the research group FRANCOGYN between January 2001 and December 2018. All patients managed for epithelial OC surgery and for whom histological slides for the review of LVSI were available, were included. The characteristics of patients with LVSI (LVSI group) were compared to those without LVSI (No-LVSI group). A Cox analysis for OS and RFS analysis was performed in all the populations.French multicenter tertiary care centers RESULTS: Over the study period, 852 patients were included in the 13 institutions. Among them, 289 patients had LVSI (33.9%). There was a significant difference in the distribution of LVSI between early and advanced stages (p 0.001). LVSI was an independent predictive factor for poorer Overall and Recurrence-Free Survival. LVSI affected OS (p 0.001) and RFS (p 0.001), LVSI affected OS and RFS for early stages (p = 0.001; p = 0.001, respectively) and also for advanced stages (p = 0.01; p = 0.009, respectively).The presence of LVSI in epithelial ovarian epithelial tumors has an impact on OS and RFS and should be included in the routine pathology examination to adapt therapeutic management, especially for women in the early stages of the disease.

We aimed to examine the effect of the squamous differentiation on survival outcomes of women with endometrioid adenocarcinoma. We retrospectively reviewed the patients with endometrioid adenocarcinoma who underwent primary surgical treatment in a tertiary referral hospital. Sixty-nine patients having squamous differentiation constituted the case group. Each woman in the case group was matched with two patients in the control group based on age, disease stage, tumour grade, lymphovascular space invasion, tumour size, myometrial invasion, type of surgery and adjuvant therapy. During the follow-up, the recurrence rates were similar between the case (5/69, 7.2%) and control (10/138, 7.2%) groups (p = 1.0). The 5-year disease-free survival rate was 90.2% for the case group and 88.6% for the control group (p = .51). The 5-year overall survival rate was 94.6% for the case group and 91.8% for the control group (p = .12). Squamous differentiation seems to have no impact on the prognosis of patients with endometrioid adenocarcinoma.IMPACT STATEMENTWhat is already known on this subject? A focus of squamous differentiation is recognised in 12.8-25% of women with endometrioid adenocarcinoma. The prognostic value of the squamous differentiation was evaluated in several previous studies. However, it could not be clarified due to the conflicting results of these studies.What do the results of this study add? The probable confounding effects of well-known prognostic factors including age at diagnosis, International Federation of Gynaecology and Obstetrics stage, tumour grade, lymphovascular space invasion, tumour size, myometrial invasion, type of surgery and adjuvant therapy were eliminated with the case-control study design in the current study. Our findings indicate that the presence of squamous differentiation does not have any prognostic effect in endometrioid type endometrial cancer.What are the implications of these findings for clinical practice and/or further research? The molecular prognosticators of endometrial cancer were extensively studied in recent years. It is likely that clinicopathological and molecular prognostic factors will be integrated for predicting prognosis as a part of routine clinical practice soon. In this context, the prognostic value of the squamous differentiation in endometrioid adenocarcinomas may further be clarified by larger and multicentric studies that utilise central pathology review.

OBJECTIVE To identify additional staging information, venous, lymphatic, and neural invasion as potential prognostic factors in colorectal cancer (CRC). STUDY DESIGN A descriptive study. Place and Duration of the Study: University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey; from May 2007 to June 2019. METHODOLOGY Retrospective analyses were performed on 855 CRC patients, who were treated with surgery. Patient and treatment characteristics, lymphovascular (LVI), and perineural (PNI) invasion were documented. The impact of LVI and PNI was determined using Cox proportional hazards model. RESULTS The cohort examined had 346 (40.5%) LVI and 150 (17.5%) PNI positive patients. After surgery, mortality was 18.4% for LVI and 8% for PNI patients. Although increased ASA score (for ASA 2 hazard ratio [HR]=0.555, p=0.001 and ASA 3-4 HR=0.723, p=0.014), adjuvant chemotherapy (HR=2.5, p

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 Although resection margin (R) status is a widely used prognostic factor after esophagectomy, the definition of positive margins (R1) is not universal. The Royal College of Pathologists considers R1 resection to be a distance less than 0.1 cm, whereas the College of American Pathologists considers it to be a distance of 0.0 cm. This study assessed the predictive value of R status after oncologic esophagectomy, comparing survival and recurrence among patients with R0 resection (> 0.1-cm clearance), R0+ resection (≤ 0.1-cm clearance), and R1 resection (0.0-cm clearance). Methods The study enrolled all eligible patients undergoing curative oncologic esophagectomy between 2012 and 2018. Clinicopathologic features, survival, and recurrence were compared for R0, R0+, and R1 patients. Categorical variables were compared with the chi-square or Fisher’s test, and continuous variables were compared with the analysis of variance (ANOVA) test, whereas the Kaplan-Meier method and Cox regression were used for survival analysis. Results Among the 160 patients included in this study, 113 resections (70.6%) were R0, 34 (21.3%) were R0+, and 13 (8.1%) were R1. The R0 patients had a better overall survival (OS) and disease-free survival (DFS) than the R0+ and R1 patients. The R0+ resection offered a lower long-term recurrence risk than the R1 resection, and the R status was independently associated with DFS, but not OS, in the multivariate analysis. Both the R0+ and R1 patients had significantly more adverse histologic features (lymphovascular and perineural invasion) than the R0 patients and experienced more distant and locoregional recurrence. Conclusions Although R status is an independent predictor of DFS after oncologic esophagectomy, the < 0.1-cm definition for R1 resection seems more appropriate than the 0.0-cm definition as an indicator of poor tumor biology, long-term recurrence, and survival.

Introduction Substantial as opposed to focal or no lymphovascular space invasion (LVSI) is proposed as an independent adverse prognostic factor in patients with early-stage endometrioid endometrial cancer (EEC). We reviewed outcomes of patients treated with adjuvant vaginal brachytherapy (VB) alone in a single institution, stratified by LVSI extent. Methods and Materials Retrospective review identified Stage I-II EEC patients receiving VB alone from 2010 to 2017. Extent of LVSI was reported as none, focal, or substantial. Kaplan–Meier estimates and Log-Rank test were used to determine significance between variables. Cox proportional hazards model was used for multivariate analyses. Results In total, 325 patients were identified with a median follow-up of 35 (23–48) months. LVSI was found in 112 patients with extent reported in 78, 45 (58%) had focal, and 33 (42%) substantial LVSI. Estimated disease-free survival for those with substantial LVSI was 73 (57–94)%, focal LVSI 89 (79–100)%, and no LVSI 94 (90–98)% at 48 months (p = 0.012). On multivariate analyses substantial LVSI was the only risk factor predictive of pelvic [HR substantial vs no: 7.2 (1.0–51.6); p = 0.048] and distant failure [HR substantial vs no: 4.4 (1.2–16.3); p = 0.027]. Both high-grade disease [HR 3 vs 1: 5.5 (1.2–25.6); p = 0.031] and extent of LVSI [HR substantial vs no: 4.4 (1.7–11.4); p = 0.002] predicted for worse disease-free survival. Discussion Substantial LVSI was the strongest adverse prognostic factor for pelvic and distant failure in this cohort of EEC patients receiving adjuvant VB alone, suggesting this subset may benefit from additional adjuvant therapy. This study underscores the importance of quantifying LVSI extent in EEC.

AimsPrimary lung adenocarcinoma consists of a spectrum of clinical and pathological subtypes that may impact on overall survival (OS). Our study aims to evaluate the impact of adenocarcinoma subtype and intra-alveolar spread on survival after anatomical lung resection and identify different prognostic factors based on stage and histological subtype.MethodsNewly diagnosed patients undergoing anatomical lung resections without induction therapy, for pT1-3, N0-2 lung adenocarcinoma from April 2011 to March 2013, were included. The effect of clinical–pathological factors on survival was retrospectively assessed.ResultsTwo hundred and sixty-two patients were enrolled. The 1-year, 3-year and 5-year OS were 88.8%, 64.3% and 51.1%, respectively. Univariate analysis showed lymphovascular, parietal pleural and chest wall invasion to confer a worse 1-year and 5-year prognosis (all pIIa, lymphovascular invasion (p=0.002) and intra-alveolar spread (p=0.009) as significant independent predictors of worse OS. Co-presence of intra-alveolar spread and solid predominance significantly reduced OS. Disease-free survival (DFS) was reduced with parietal pleural (p=0.0007) and chest wall invasion (pConclusionsOur study demonstrates that solid predominant adenocarcinoma, intra-alveolar spread and lymphovascular invasion confer a worse prognosis and should be used as a prognostic tool to determine appropriate adjuvant treatment.

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.

Lip abscess is a rare condition encountered in clinical practice. Generally, it may be due to an infective agent, such as virus, bacteria, entering through a skin wound, or it can be seen through hematogenous spread when there is a serious underlying condition such as a general condition disorder or immunodeficiency. It requires rapid diagnosis and treatment as it may cause significant complications in terms of localization and lymphovascular drainage. In this case report, an 18-year-old male patient with unilateral lip abscess that regressed rapidly with external drainage and antibiotic therapy is presented with imaging and clinical-laboratory findings.

Background and objectives The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC). Methods Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018. Results Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS. Conclusions The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.

Background/aim To investigate the utility of preoperative serum cancer antigen 125 (CA 125) levels in type 1 endometrial carcinoma (EC) as a marker for determining poor prognostic factors and survival. Material and methods All patients with endometrial cancer, who had been treated between 2012 and 2020, were retrospectively reviewed, and finally, 256 patients with type 1 endometrium carcinoma were included in the study. The relationship between the clinicopathological characteristics, CA 125 level, and survival rates were analyzed. The cut-off value for the preoperative serum CA 125 level was defined as 16 IU/L. Results The median serum CA 125 levels were significantly higher in patients with deep myometrial invasion, lymph node metastasis, lymphovascular space invasion, cervical stromal and adnexal involvement, advanced stage, positive peritoneal cytology, recurrence, and adjuvant therapy requirement. Serum CA 125 cut-off values determined according to clinicopathologic factors ranged from 15.3 to 22.9 IU/L (sensitivity 61%–77%, specificity 52%–73%). The disease-specific survival rate was significantly higher in patients with CA 125 levels < 16 IU/L (P = 0.047). Conclusion The data showed that choosing a lower threshold value for the CA 125 level (16 IU/L) instead of 35 IU/L, could be more useful in type 1 EC patients with negative prognostic factors.

BACKGROUNDS AND OBJECTIVES Lymphovascular invasion (LVI) has shown evidence of an association with worse survival in high-grade osteosarcoma patients. The purpose of this investigation was to prognosticate LVI as a predictor of survival. METHODS This was a retrospective review of high-grade, localized osteosarcoma patients over a consecutive 10-year period. Proportional hazards regression was used to identify prognostic factors. Cumulative mortality incidence was estimated with recurrence as a competing risk. RESULTS Forty-two cases with a median follow-up of 64 months (range, 6-158 months) were reviewed. LVI was present in 21.4% (n = 9) cases. The five- and ten-year survivals in LVI (+) were 40% and 20%, compared to 93% and 81% in LVI (-), respectively (p

Solid pseudopapillary neoplasms (SPNs) of the pancreas have low malignant potential. However, malignant SPNs are not fully understood.To evaluate risk factors affecting malignant potential, the clinicopathologic features of 375 surgically resected SPNs were compared.Fifty (13.3%) had malignant histologic features. Twenty-seven and 22 had perineural and lymphovascular invasions, respectively. Adjacent organ invasion was noted in 9 cases. Recurrence occurred in 8 cases. The median recurrence time after surgical resection was 67 months and was associated with a higher pT category (P = 0.001), lymphovascular invasion (P 0.001), and synchronous metastasis (P 0.001). SPN patients with malignant histologic features had worse recurrence-free survival (RFS; 10-year survival rate, 73.2%) than those without malignant histologic features (96.3%; P = 0.01). Patients with a higher pT category (P = 0.04), synchronous metastasis (P 0.01), and lymphovascular invasion (P 0.01) had worse RFS. Lymphovascular invasion (P = 0.042) and a higher T category (P = 0.002) were poor prognostic factors for recurrence.Lymphovascular invasion and a higher T category were worse prognostic factors for recurrence in SPN patients with malignant histologic features. For SPN patients with malignant histologic features, a longer follow-up may be required.

The survival outcomes of pT1N0–3 or pT2–3N0 gastric cancer after curative resection are favorable without adjuvant chemotherapy. However, some patients develop recurrence and details of these recurrences remain unclear. This study aimed to evaluate the prognostic factors in patients with pT1N0–3 or pT2–3N0 gastric cancer. We retrospectively reviewed the medical records of 1219 patients with pT1N0–3 or pT2–3N0 gastric cancer who underwent curative gastrectomy without neoadjuvant or adjuvant chemotherapy between April 2007 and March 2012 at Cancer Institute Hospital. This cohort included 895 pT1N0, 73 pT1N1, 23 pT1N2, 6 pT1N3, 130 pT2N0, and 92 pT3N0 patients. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) for pT1N0–3 and pT2–3N0 gastric cancer were 98.9% (95% CI 98.1–99.4) and 97.7% (95% CI 96.7–98.4), respectively. Age (HR 3.56, 95% CI 2.10–6.03) and lymphovascular involvement (hazard ratio (HR) 2.98, 95% CI 1.76–5.04) were independent prognostic factors in a multivariate analysis for RFS. The 5-year RFS for patients aged ≥75 years or with lymphovascular involvement were 94.4% (95% CI 89.8–97.0) and 95.1% (95% CI 92.5–96.8), respectively. The survival outcomes of pT1N0-3 and pT2-3N0 were excellent, even in patients with aged >75 years or lymphovascular involvement which were risk factors. However, the sample size of T1N3 gastric cancer is small, so larger sample size and risk factor analysis are required.

To evaluate the contributory value of positron emission tomography (PET)-intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the prediction of lymphovascular space invasion (LVSI) in patients with cervical cancer without lymphatic metastasis. A total of 90 patients with cervical cancer without signs of lymph node metastasis on PET/MRI were enrolled in this study. The tumours were classified into LVSI-positive (n = 25) and LVSI-negative (n = 65) groups according to postoperative pathology. The PET-derived parameters (SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) and IVIM-derived parameters (ADCmean, ADCmin, Dmean, Dmin, f, D* and gross tumour volume (GTV)) between the two groups were evaluated using a Student’s t test (Mann-Whitney U test for variables with a nonnormal distribution) and receiver operating characteristic (ROC) curves. The optimal combination of PET/MR parameters for predicting LVSI was investigated using univariate and multivariate logistic regression models and evaluated by ROC curves. The optimal cutoff threshold values corresponded to the maximal values of the Youden index. A control model was established using 1000 bootstrapped samples, for which the performance was validated using calibration curves and ROC curves. PET-derived parameters (SUVmax, SUVmean, MTV, TLG) and IVIM MRI-derived parameters (Dmin, ADCmin, GTV) were significantly different between patients with and without LVSI (P < 0.05). Logistic analyses showed that a combination of TLG and Dmin had the strongest predictive value for LVSI diagnosis (area under the curve (AUC), 0.861; sensitivity, 80.00; specificity, 86.15; P < 0.001). The optimal cutoff threshold values for Dmin and TLG were 0.58 × 10−3 mm2/s and 66.68 g/cm3, respectively. The verification model showed the combination of TLG and Dmin had the strongest predictive value, and its ROC curve and calibration curve showed good accuracy (AUC, 0.878) and consistency. The combination of TLG and Dmin may be the best indicator for predicting LVSI in cervical cancer without lymphatic metastasis.

BACKGROUND AND OBJECTIVES We sought to evaluate the impact of lymphovascular invasion (LVI) and perineural invasion (PNI) on survival outcomes in gastric cancer patients treated with preoperative therapy. METHODS Patients with gastric cancer treated with preoperative therapy and potentially curative resection were stratified according to the presence of LVI, PNI, or both. Kaplan-Meier and Cox regression analyses were used to evaluate the impact on overall survival (OS) and disease-free survival (DFS). RESULTS The study included 281 patients, of whom 93 (33%) had LVI, 69 (25%) had PNI, 51 (18%) had both LVI and PNI, and 170 (61%) had neither. LVI and PNI were each associated with higher ypT and ypN categories and more positive lymph nodes (all p

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC). Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis. Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the “LVSI index” as “TD×%MMI×tumor grade×cervical stromal involvement.” The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200. Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.

Background/aim The rate of lymph node metastasis (LNM) of colorectal carcinoma (CRC) with a submucosal (SM) invasion depth of 1000 µm or more can reach 12.5%, which is the most common reason for additional resection in daily practice. Other studies have reported that the rate of LNM is less than 2%, regardless of the depth of invasion, if the lesions show good histology, lymphovascular infiltration is negative, and tumor budding is limited. The purpose of this study was to investigate new risk factors for LNM in T1b colorectal cancer. Patients and methods The 239 patients who were diagnosed with pathological T1b CRC after colorectal surgical resection at the Osaka Police Hospital in Japan between January 2008 and December 2018 were retrospectively reviewed in this study. Results The LNM rate was 11.3% (27/239). The variables identified as being significant factors using multivariate analysis were: i) lymphatic invasion (Ly)-positive [odds ratio (OR)=5.97; 95% confidence interval (CI)=2.27-15.74], ii) female gender (OR=3.49; 95%CI=1.38-8.85), and iii) left-sided colorectal involvement (OR=4.98; 95%CI=1.22-20.39). If none of these risk factors were present with T1b, the LNM rate was 0% (0/28). Conclusions Ly-positive, female gender, and left-sided colorectal involvement could be risk factors for LNM in T1b CRC.

ObjectiveAdjuvant treatment remains a controversial issue for intermediate-risk cervical cancer. The aim of this study was to compare the prognosis of patients who underwent no adjuvant treatment, pelvic radiotherapy alone, or concurrent chemoradiotherapy after radical hysterectomy for intermediate-risk, early-stage cervical cancer.MethodsPatients with stage IB1–IIA2 (FIGO 2009) cervical squamous cell carcinoma treated with radical hysterectomy and pelvic lymph node dissection, with negative lymph nodes, surgical margins, or parametria, who had combined intermediate risk factors as defined in the Gynecologic Oncology Group trial (GOG-92; Sedlis criteria) were included in the study. Recurrence-free survival and disease-specific survival were compared.ResultsOf 861 patients included in the analysis, 85 patients received no adjuvant treatment, 283 patients were treated with radiotherapy, and 493 patients with concurrent chemoradiotherapy. After a median follow-up of 63 months (IQR 45 to 84), adjuvant radiotherapy or concurrent chemoradiotherapy was not associated with a survival benefit compared with no adjuvant treatment. The 5-year recurrence-free survival and corresponding disease-specific survival were 87.1%, 84.2%, 89.6% (p=0.27) and 92.3%, 87.7%, 91.4% (p=0.20) in the no adjuvant treatment, radiotherapy alone, and concurrent chemoradiotherapy groups, respectively. Lymphovascular space invasion was the only independent prognostic factor for both recurrence-free survival and disease-specific survival. Additionally, significant heterogeneity exists in Sedlis criteria: higher risk of relapse (HR=1.88; 95% CI 1.19 to 2.97; p=0.007) and death (HR=2.36; 95% CI 1.41 to 3.95; p=0.001) occurred in patients with lymphovascular space invasion and deep 1/3 stromal invasion compared with no lymphovascular space invasion, middle or deep 1/3 stromal invasion, and tumor diameter ≥4 cm.ConclusionsRadical hysterectomy alone without adjuvant treatment may achieve a favorable survival for patients with intermediate-risk cervical cancer as defined by Sedlis criteria. Criteria for adjuvant treatment in patients without high risk factors need to be further evaluated.

Objective: The purpose of this case-control study was to investigate the effect of lymphovascular space invasion on recurrence patterns and survival in patients with stage IIIC endometrioid type endometrial cancer.Study Design: A multicenter, retrospective, department database review was performed to identify lymphovascular space invasion-negative and lymphovascular space invasion-positive stage IIIC endometrioid endometrial cancer at five gynecological oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. Cases and controls were matched in terms of age at diagnosis, grade of tumor, depth of myometrial invasion, sub-stage and adjuvant treatment.Results: Forty-one patients in the case group and 82 patients in the control group were eligible for the study. The 5-year OS rates were 94.4% in the lymphovascular space invasion-negative group and 77.2% in the LVSI-positive group (p=0.058). Advanced age (58 years) (HR 3.73; 95% CI: 1.19-11.69, p=0.02), grade 3 tumor (HR 2.57; 95% CI: 1.002-6.62, p=0.048) and cervical involvement (HR 2.62; 95% CI: 1.03-6.67, p= 0.04) appeared to be as independent predictors of decreased overall survival (OS). There was a trend towards statistical significance between the presence of lymphovascular space invasion and OS in regression analysis (HR 3.10; 95% CI 0.90-10.67, p=0.05). Recurrence rates were 17.0% (7/41) and 24.4% (20/82) in lymphovascular space invasion-negative and lymphovascular space invasion-positive groups, respectively (p=0.48). There were 5 cases of retroperitoneal recurrences in the lymphovascular space invasion-positive group and no retroperitoneal recurrence among lymphovascular space invasion-negative women.Conclusion: Lymphovascular space invasion status seems to be of borderline significance for OS in stage IIIC endometrioid endometrial cancer and impacts recurrence patterns as retroperitoneal recurrences are strongly related to positive lymphovascular space invasion status.

Background: Survivin, an anti-apoptotic protein has been of importance in colon carcinoma patient. Here we studied the prevalence of Survivin biomarker among cases of colon carcinoma and its relationship with other prognostic indicators. Design: Tissue samples from 102 patients with colon carcinoma were studied. H&E stain and immunohistochemistry were performed and evaluated. Immuno-histochemistry expression was sought according to IRS Scoring System (Immunoreactivity Scoring) for stain intensity and percentage positive cells. Survivin expression was also correlated with age at diagnosis, gender, grade, nodal status, lympho-vascular and perineural invasion, resection margins, Tumor stage (TNM) and Group Stage. Result and discussion: Survivin was expressed in high grade and stage tumors and showed significant association (p value= 0.002). Survivin expression was positive in lymph node positive tumors and showed significant association (p value= 0.002). Survivin was expressed in tumors with lympho-vascular and perineural invasion and showed significant association (p value= 0.02 and 0.001) respectively. Age at diagnosis showed significance of p=0.03 whereas Gender (Male/Female) and resection margins did not show any association with Survivin expression. Conclusion: Survivin expression increases as the tumor grade worsens in colon cancer and is maintained in approximately all high group staged tumors (TNM Staging) along with tumors showing lymphovascular and perineural invasion. Gender does not have any association.

Aim Neuroendocrine tumors (NETs) are one of the subtypes of neuroendocrine neoplasms and are defined as epithelial neoplasms with predominant neuroendocrine differentiation. The aim of this study was to clarify the clinicopathological characteristics of colorectal NETs through a nationwide retrospective study in Japan. Methods This multicenter retrospective cohort study of NETs in Japan was conducted by the study group of the Japanese Society for Cancer of the Colon and Rectum. In this study, we aimed to clarify the characteristics of Japanese patients with colorectal NETs. This cohort study included patients with colorectal NETs who were treated from January 2011 to December 2015. Results Most NETs developed in the lower rectum. Predictive factors of lymph node metastasis included size (>10 mm), depth of invasion (muscular propria or greater), NET grade (NET G2), depressed lesion of the tumor, and lymphovascular infiltration. In particular, depressed lesion of the tumor and lymphovascular infiltration were independent predictive factors of lymph node metastasis. The presence of an increased number of these predictive factors increased the lymph node metastasis rate. Conclusion Surgical resection with lymph node dissection is considered in the colorectal NETs patients with predictive factors of lymph node metastasis, the number of which is correlated with incidence of lymph node metastasis., This Japanese multicenter retrospective study revealed clinicopathological characteristics and the risk factors of lymph node metastasis in colorectal neuroendocrine tumors.

The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines indicate lymphovascular invasion—evaluated by hematoxylin and eosin (HE) staining—as a surgical requirement after endoscopic submucosal dissection (ESD) in T1 colorectal carcinoma (CRC) patients; however, immunohistochemical evaluation may be superior. This study aimed to clarify the significance of immunohistochemical lymphovascular evaluation as an indicator for additional surgery of T1 CRC after ESD, and assessed the guidelines’ adequacy, even when evaluating through immunostaining. Patients with T1 CRC who underwent ESD were enrolled across three institutions between January 2012 and December 2017. Immunohistochemical lymphovascular evaluation was performed. Clinicopathological features, pathological evaluations, and surgery indications were recorded. Univariate and multivariate logistic regression identified risk factors for lymph node (LN) metastasis of T1 CRC after ESD. Among 370 patients with T1 CRC, recurrence, 5-year overall survival, and 5-year disease specific survival rates were 1.6%, 94.6%, and 99.5%, respectively. Six patients (1.6%) experienced recurrence, five of whom underwent additional surgery. Those with no risk factors did not exhibit recurrence. A total of 215 (58.1%) patients underwent additional surgery after ESD, 21 (9.7%) of whom exhibited LN metastasis. Among 16 patients who underwent additional surgery due to lymphovascular invasion, three (18.8%) had LN metastasis. Multivariate logistic regression analysis identified lymphatic invasion as a significant risk factor for LN metastasis (odds ratio 3.9, 95% confidence interval 1.0–14.6, P = 0.0421). The JSCCR guidelines have clinical validity, and immunohistochemical lymphatic evaluation findings potentially predict LN metastasis for T1 CRC after ESD.

Extramural venous invasion (EMVI) is an established independent prognostic factor in colorectal carcinoma where it is linked to hematogenous spread (i.e., liver metastases), influencing the decision for adjuvant chemotherapy. However, its prognostic significance in small intestinal neuroendocrine tumors (NETs) has not been studied, nor is it routinely assessed or reported. We reviewed primary small bowel NETs (14 jejunum, 82 ileum, 8 not specified) from 104 patients (52 women; median age 60.5, range: 24–84). EMVI was identified in 58 cases (55.8%), including in 13 of 21 equivocal cases using an elastin stain. In univariate analysis, EMVI was associated with lymphovascular and perineural invasion, tumor stage, and lymph node and distant metastases, whereas in multivariate analysis, only distant metastases remained significant (p

ObjectiveLow grade serous ovarian cancers characterize a unique clinical pattern and likely less frequent incidence of lymphatic metastasis. The expression level of Ki67 is associated with differences in prognosis and therapy outcome. However, its expression in combination with lymphovascular space invasion has not been evaluated in the prediction of lymphatic metastasis.MethodsPatients with low grade serous ovarian cancer were identified in an institutional database. Patients with primary low grade serous ovarian cancer diagnosed and/or treated at our center between September 2000 and December 2018 were identified. Receiver operator characteristics curve analysis was performed to find the cut-off values of per cent Ki67 to discriminate patients with lymph node metastasis. The association between the presence of lymphovascular space invasion and lymph node involvement was analyzed.ResultsA total of 109 patients with primary low grade serous ovarian cancer were identified in our institution's database. Of these, 72 (66.1%) patients underwent primary surgery with pelvic and para-aortic lymph node dissection. Complete data for Ki67 expression and lymphovascular space invasion were obtained for 61 (84.7%) of these patients. Among them, 37 (60.7%) patients had lymph node metastasis. The presence of lymphovascular space invasion was associated with an increased risk of lymph node metastases (odds ratio (OR)=12.78, 95% confidence interval (CI) 3.15 to 51.81; p65 years, peritoneal carcinomatosis, and ascites>500 mL, lymphovascular space invasion remained a significant risk factor for lymphatic metastases (OR=35.11, 95% CI 2.38 to 517.69; p=0.010). Ki67 ≥6% was associated with a higher risk of lymphovascular space invasion (OR=3.67, 95% CI 1.26 to 10.64; p=0.017). No significant correlation between Ki67 expression level and nodal metastases was found (OR=2.19, 95% CI 0.76 to 6.26; p=0.14). Neither presence of lymphovascular space invasion or nodal metastases was associated with a statistically poorer prognosis.ConclusionsWe showed an association between lymphovascular space invasion, Ki67 expression, and risk of lymph node metastasis in primary low grade ovarian cancer. Further prospective trials evaluating lymphovascular space invasion and Ki-67 as predictors of lymph node metastasis are needed.