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Introduction: There is an ongoing need to identify various pathological factors that can predict various survival parameters in patients with upper tract urothelial carcinoma (UTUC). With this review, we aim to scrutinize the impact of several pathological factors on recurrence free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) in patients with UTUC. Materials and Methods: Systematic electronic literature search of various databases was conducted for this review. Studies providing multivariate hazard ratios (HR) for various pathological factors such as tumor margin, necrosis, stage, grade, location, architecture, lymph node status, lymphovascular invasion (LVI), carcinoma in situ (CIS), multifocality and variant histology as predictor of survival parameters were included and pooled analysis of HR was performed. Results: In this review, 63 studies with 35.714 patients were included. For RFS, all except tumor location (HR 0.94, p=0.60) and necrosis (HR 1.00, p=0.98) were associated with worst survival. All the pathological variables except tumor location (HR 0.95, p=0.66) were associated with worst CSS. For OS, only presence of CIS (HR 1.03, p=0.73) and tumor location (HR 1.05, p=0.74) were not predictor of survival. Conclusions: We noted tumor grade, stage, presence of LVI, lymph node metastasis, hydronephrosis, variant histology, sessile architecture, margin positivity and multifocality were associated with poor RFS, CSS and OS. Presence of CIS was associated with poor RFS and CSS but not OS. Tumor necrosis was associated with worst CSS and OS but not RFS. Tumor location was not a predictor of any of the survival parameters.

Purpose: To analyse the risk of inguinal lymph node (ILN) metastases in T1G2 penile cancer stratified by lymphovascular invasion (LVI), perineural invasion (PNI) and tumour size. Methods: Retrospective study of men with localised T1G2 penile cancer with non-palpable lymph nodes and no local recurrence during follow-up at six European institutional high-volume centres was performed. ILN involvement was defined as cancer detected during ultrasound-guided fine-needle aspiration cytology, core needle biopsy, dynamic sentinel lymph node biopsy, ILN dissection or inguinal recurrence during follow-up. Uni- and multivariable logistic regression analyses were performed. Results: In the cohort of 554 men with T1G2 penile cancer, from 6 European institutions, ILN metastases were observed in 46/554 men (8%, 95% confidence interval (CI) 6–11%). Men with both, LVI- and PNI- primary cancers had the lowest risk of ILN involvement (6%) whereas men with LVI + or PNI + showed ILN metastases in 22% and 30%. In multivariable regression, men with LVI + or PNI + had higher odds for ILN metastases compared to men with LVI- and PNI- (OR 3.9, 95% CI 1.6–9.0, p value < 0.01) Tumour size was not associated with ILN risk (OR 1.01 95% CI 0.99–1.04, p = 0.17). Conclusion: Approximately, one out of ten men with T1G2 overall and one out of four men with either LVI + or PNI + still have ILN metastases despite being clinically node negative. Therefore, invasive ILN staging should strongly be recommended in T1G2 with LVI + or PNI + but importantly, must be discussed in patients with T1G2 with LVI- or PNI-.

The choice of subsequent treatment for intermediate-risk rectal tumors after transanal endoscopic microsurgery between adjuvant chemoradiotherapy and total mesorectal excision is controversial. The present study aimed to compare survival and functional outcome between these 2 strategies.This retrospective study included intermediate-risk patients with early rectal cancer after transanal endoscopic microsurgery in our center between 2010 and 2017. Patients were divided into adjuvant treatment and total mesorectal excision groups. Intermediate risk was defined as pT1 with lymphovascular invasion, poor differentiation, or large diameter (3-5 cm) or pT2 with small diameter (3 cm). The study was based on follow-up data on survival and results from distributed validated scales for functional outcome.Postoperative overall survival and disease-free survival were comparable between the groups (P = .619 and P = .712, respectively). Pathological T stage was an independent risk factor for disease-free survival (hazard ratio 3.09, 95% confidence interval 1.66-4.18, P = .044). Anorectal symptoms, such as buttock pain, were significantly prevalent in the total mesorectal excision group (P = .030). In addition, the total mesorectal excision group presented with poorer bowel function, including stool urgency (P.001), bowel frequency (P = .016), severity of low anterior resection syndrome (P = .039) and total low anterior resection syndrome score (P = .040). Except for a lower score of vaginal lubrication in the total mesorectal excision versus the adjuvant treatment group, sexual function was similar between the groups.Similar to total mesorectal excision, adjuvant chemoradiotherapy is an alternative option for intermediate-risk early rectal cancer after transanal endoscopic microsurgery and is associated with similar survival outcomes and better bowel function.

Background Lymphovascular invasion (LVI) is an aggressive histologic finding but is excluded from current staging systems due to lack of demonstrated independent prognostic significance. Objective To evaluate the impact of LVI on CSCC tumor outcomes. Methods 10,707 CSCC tumors from a 20-year retrospective multicenter cohort were stratified by presence (LVI+) or absence (LVI-) of LVI. Outcomes (local recurrence, in transit metastasis, nodal metastasis, disease specific death) were compared based on low (Brigham and Women’s Hospital (BWH) stage T1/T2a) and high (BWH T2b/T3)-tumor stage. Results Of the 10,707 tumors, 78 tumors had LVI. Analysis of low-stage BWH tumors showed the LVI+ group had a significantly higher 5-year cumulative incidence of LR (LVI+: 12.3% vs. LVI-: 1.1%, p Limitations Retrospective study design. Conclusion LVI+ CSCCs have a higher rate of metastasis and death at 5-years. Future staging systems should consider incorporating LVI.

Purpose Higher energy (>6 MV) photons reduce dose inhomogeneity with breast tangent beams, thereby reducing late breast toxicity, but skin and superficial tissue sparing by higher energy beams raises concerns about local recurrence (LR) risk. This study aimed to determine whether beam energy and surgical bed-to-skin distance affect LR. Methods and Materials This population-based study included newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with breast-conserving surgery and adjuvant whole breast radiotherapy without bolus or beam spoilers. The primary endpoint was the cumulative incidence of LR (CILR). A multivariable analysis (MVA) included mean beam energy, age, T-stage, nodal status, overall stage, lymphovascular invasion (LVI), grade, margin status, extensive intraductal component (EIC), breast cancer subtype, hormone therapy and chemotherapy. In a subgroup with contoured surgical beds, another MVA included surgical bed-to-skin distance. Results The cohort consisted of 10,083 women treated from 2002 to 2011, 327 with 4MV, 6,006 with 6 MV, 2,083 with >6-10 MV and 1,667 with >10 MV tangents. The median follow-up time was 11.1 years. The 10-year CILR was 3.1% [95% confidence interval 1.6,5.4] with 4 MV, 2.8% [2.4,3.3] with 6 MV, 4.2% [3.4,5.3] with >6-10 MV and 2.6% [1.9,3.5] with >10 MV. On MVA of the entire cohort, LR risk was increased with positive margins, LVI, EIC, and lack of hormone therapy, but was not associated with beam energy (HR = 1.01 [0.96,1.05], p = 0.8). On MVA of 3,359 patients with contoured surgical beds, LR risk was not associated with surgical bed-to-skin distance (HR = 1.00 [0.99,1.02], p = 0.8). Conclusions Use of higher breast tangent beam energies is not associated with increased risk of local recurrence, including in cases with surgical beds that are close to the skin.

Summary Purpose In the ACOSOG Z0011 trial, patients with primary breast cancer and 1–2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. Methods Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-Francois Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. Results Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR) = 6.1; 95% confidence interval (CI): 1.4-26.7; P = 0.02)) and only one SLN removed (OR = 9.1; 95%CI: 2.2-33.3; P = 0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR = 5.1; 95%CI: 1.2-22.2; P = 0.03) was associated with the failure to perform completion ALND when recommended. Conclusion Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

BACKGROUND Hormone receptor-positive, human epidermal growth factor receptor II (HER2)-negative luminal B1 breast cancer is associated with a higher risk of disease relapse than luminal A breast cancer. Therefore, we assessed and compared the distant metastasis pattern and clinical outcomes associated with luminal B1 and luminal A breast cancer in an Asian population. METHODS In this observational study, we assessed patients with estrogen receptor-positive, HER2-negative breast cancer who underwent surgery from 2009 to 2016. Patients were classified into luminal A or luminal B1 subsets via immunohistochemical analysis. Disease-free survival, post-metastasis survival, and overall survival were estimated; time to disease relapse and patterns of distant metastasis were compared. Risk of relapse and mortality were assessed using Cox proportional hazards model. RESULTS Patients with luminal B1 breast cancer (n = 677) were significantly younger and had larger tumors and a higher degree of affected axillary lymph nodes, lymphovascular invasion, and tumor necrosis than those with luminal A breast cancer (n = 630). Higher rates of local recurrence and distant metastasis were observed for luminal B1 (both p < 0.05); however, no difference was observed in the specific distant metastatic sites. We observed a significant increase in disease relapse risk in luminal B1 patients compared with that in luminal A (hazard ratio: 2.157, 95% confidence interval: 1.340-3.473, p < 0.05). Patient age, tumor size, stage, lymphovascular invasion, and receiving chemotherapy and hormone therapy were independent risk factors for metastasis and recurrence. Only the luminal B1 subtype (hazard ratio: 5.653, 95% confidence interval: 1.166-27.409, p < 0.05) and stage (hazard ratio: 3.400, 95% confidence interval: 1.512-7.649, p < 0.05) were identified as independent risk factors for post metastatic mortality. CONCLUSION Luminal B1 breast cancer has aggressive tumor biology compared with luminal A breast cancer in the follow-up period. However, there was no significant difference in the disease relapse pattern between the groups.

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

Lung adenocarcinomas manifesting as subsolid nodules usually have a favorable prognosis. This study aimed to have a comprehensive investigation of the radiological and clinicopathologic features and oncological outcomes of subsolid nodules. Between March 2010 and December 2015, 865 patients with surgically resected clinical IA subsolid lung adenocarcinoma were retrospectively reviewed. Patients were classified into the pure ground-glass nodules (GGN) (pGGN [n = 358], without solid component on lung and mediastinal windows), heterogeneous GGN (hGGN [n = 65], only with solid components on lung window), and real part-solid nodule (rPSN [n = 442], with solid component on both lung and mediastinal windows) groups. The clinicopathological features and survival time of the three groups were compared between groups. There was a significant increase in median tumor size (P0.001), solid component size measured at lung window (LW-SCS) (P0.001), and the proportion of invasive adenocarcinoma subtypes (P0.001) from pGGNs to hGGNs to rPSNs. After adjustment for LW-SCS, adenocarcinomas with predominant lepidic patterns were still more common in hGGNs than in rPSNs (P = 0.009). Patients with rPSNs had a significantly worse recurrence-free survival (RFS) than those with pGGNs and hGGNs (5-year: 91.9% versus 100% versus 100%, P0.001). Multivariate Cox analyses revealed that gender (both P0.05) and clinical T category (based on lung window [LW-cT] [P = 0.002] or mediastinal window [MW-cT] [P0.001]) were independent prognostic factors of RFS in the rPSN group. HGGNs represented as an intermediate subtype between pGGNs and rPSNs. Both pGGNs and hGGNs had excellent outcomes, while rPSNs exhibited a worse prognosis than them. Clinical T category and gender had prognostic implications for rPSNs.

Background/Aims: Adjuvant chemotherapy is the standard of care for resected stage II-IIIA non-small cell lung cancer (NCSLC). The efficacy of adjuvant chemotherapy in stage IB (< 4 cm) NSCLC with high-risk factors is controversial.Methods: This retrospective multicenter study included 285 stage IB NSCLC patients with high-risk factors according to the 8th edition tumor, node, metastasis (TNM) classification from four academic hospitals. High-risk factors included visceral pleural invasion, vascular invasion, lymphatic invasion, lung neuroendocrine tumors, and micropapillary histology patterns.Results: Of the 285 patients, 127 (44.6%) were included in the adjuvant chemotherapy group and 158 (55.4%) were included in the non-adjuvant chemotherapy group. The median follow-up was 41.5 months. Patients in the adjuvant chemotherapy group had a significantly reduced recurrence rate and risk of mortality than those in the non-adjuvant chemotherapy group (hazards ratio, 0.408; 95% confidence interval, 0.221 to 0.754; p = 0.004 and hazards ratio, 0.176; 95% confidence interval, 0.057 to 0.546; p = 0.003, respectively). Adjuvant chemotherapy should be particularly considered for the high-risk factors such as visceral pleural involvement or vascular invasion. Based on the subgroup analysis, adjuvant chemotherapy should be considered when visceral pleural involvement is present, even if the tumor size is < 3 cm.Conclusions: Adjuvant chemotherapy may be useful for patients with stage IB NSCLC with high-risk factors and is more relevant for patients with visceral pleural involvement or vascular invasion.

Contains fulltext : 249895.pdf (Publisher’s version ) (Open Access) AIM: The aim of this study was to evaluate interobserver variability between individual pathologists and a panel of pathologists in the histopathological assessment of advanced colorectal neoplasms in the Dutch bowel cancer screening population. METHODS AND RESULTS: Histological slides of adenomas with high-grade dysplasia and early colorectal carcinomas (CRC) from 20 different laboratories were reviewed by the pathology panel of the Dutch bowel screening programme. Interobserver variability was reported by descriptive statistics. In addition, potential clinical consequences of discrepancies were evaluated. A total of 104 cases of adenomas with high-grade dysplasia and 83 early CRCs were reviewed. Discrepancies were observed in 41 of 104 (39.4%) adenoma cases, which potentially had clinical consequences in 16 (15.4%) cases. For CRC, discrepancies were shown in 44 of 83 cases (53.0%) and would have potentially led to alternative treatment strategies in 25 (30.1%) cases. Most frequently, discrepancies were observed in the assessment of lymphovascular invasion (23 of 73 cases, 31.5%). CONCLUSION: This study showed that considerable interobserver variability is present in the histopathological assessment of advanced colorectal neoplasia, which may impact upon treatment choices. Additional stains and education, as well as intercollegial consultation, might decrease this variability.

Tumor budding is a significant prognostic indicator for poor survival of several solid tumors. However, due to the lack of a standard scoring system, its clinical application for biliary tract cancer (BTC) is limited.To identify the prognostic significance of tumor budding in BTC.Tumor budding was associated with poor histologic differentiation, lymphovascular invasion, perineural invasion, lymph node metastasis, positive surgical margin, etc. Tumor budding was a predictor of poor OS in univariate (HR: 4.36; 95% CI 3.15 to 6.02; P 0.001) and multivariate (HR: 2.95; 95% CI 2.28 to 3.80; P 0.001) analysis. Similarly, it was also a predictor of poor DFS in univariate (HR: 3.26; 95% CI 2.12 to 4.99; P 0.001) and multivariate (HR: 3.21; 95% CI 1.90 to 5.40; P 0.001) analysis. In addition, tumor budding was also associated with advanced T-stage, poor histologic differentiation, lymph node metastasis, positive resection margin, lymphatic invasion, vascular invasion, and perineural invasion.Results of our study have shown that tumor budding is a strong predictor of poor survival for BTC. The clinical utility of tumor budding as a prognostic marker for BTC should be considered after developing a standard international consensus based on the current evidence.

AIMS The recent changes in the American Joint Commission on Cancer-8th edition (AJCC-8E) pT2 and pT3 tumor definitions for penile cancer need robust validation studies. A recent study redefined and modified the pT2 and pT3 stages incorporating the histopathological variables (tumor grade, lymphovascular invasion, perineural invasion) similar to that used in the current AJCC-8E pT1 stage tumor subclassification. In this study, we validate and compare this proposed staging with the AJCC staging systems, on an external dataset. METHODS AND RESULTS The dataset from a previously published study was obtained. pT2 and pT3 stages were reconstructed as per AJCC 7th edition (AJCC-7E), AJCC-8E, and the proposed staging. The staging systems were correlated with nodal metastasis, disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS). All systems were compared using receiver operating characteristics (ROC) curves. A total of 281 cases formed the study cohort. AJCC-8E (p=0.031) and the proposed staging (p=0.003) correlated with nodal metastasis on adjusted analysis, the latter with a better strength of association (AJCC-8E, γ= -.471, proposed, γ= -.625). On adjusted analysis, all the staging systems had a significant correlation with DFS, while only AJCC-8E and the proposed staging correlated with CSS and OS. On ROC curve analysis, the proposed staging had the highest area under the curve and was the only staging system to statistically correlate with all the outcome variables. CONCLUSIONS The proposed staging for pT2/pT3 tumor stages in penile cancer may improve the prognostic and predictive ability.

The inception of the National Health Service Bowel Cancer Screening Programme in England in 2006 highlighted the fact that the differential diagnosis between the presence of epithelial misplacement and adenocarcinoma occurring in colorectal adenomas is problematic. The pathology Expert Board (EB) was created to facilitate the review of difficult cases by a panel of three experienced gastrointestinal pathologists. This article describes a review of the work of the EB over a 4-year period (2017-2020).Four hundred and thirty polyps were referred to the EB from 193 pathologists and 76 hospitals during this time. The EB diagnosis was benign for 67%, malignant for 28%, and equivocal for 2% (with no consensus in the remainder). The most common diagnosis change made by the EB was from malignant to benign-made in 50% of polyps referred with an initially malignant diagnosis. The level of agreement between the individual EB members was 'good' (kappa score of 0.619) but that between the EB and the referring diagnosis was 'poor' (kappa score of 0.149). Data from one EB member indicated that the presence of lamina propria, features of torsion and cytological similarity between the superficial and deep glands were predictors of a benign diagnosis, whereas the presence of irregular neoplastic glands, a desmoplastic reaction and lymphovascular invasion were commonly observed features in polyps with a malignant diagnosis.Diagnostic agreement between EB members is better than that between the EB and referring pathologists. There was a consistent trend for the EB to change diagnoses from malignant to benign.

Objective To evaluate the prognostic and predictive significance of lymphovascular invasion (LVI) and lymph node metastasis of intratumoral budding (ITB) and its correlation with clinicopathological parameters in patients with cervical cancer. Methods Total 151 patients with cervical cancer who underwent radical hysterectomy with pelvic and/or paraaortic lymphadenectomy were included. We assessed the status of ITB and peritumoral budding (PTB) in all available hematoxylin and eosin-stained specimens. Univariate and multivariate analyses were performed for ITB, PTB, and other clincopathological parameters as predictors of recurrence. Results ITBhigh (≥3TB/HPF) was significantly associated with large tumor size, deep stromal invasion, LVI, parametrial invasion, and lymph node metastasis. The numbers of ITBs and PTBs were positively correlated (r2 = 0.754, p Conclusion ITBhigh is an independent prognostic factor for tumor recurrence. ITB is a surrogate marker for predicting LVI in cervical cancers. The evaluation of ITB may be readily applied in the clinical setting for improved prognosis and to guide the clinical management of patients with cervical cancer.

Please see the Editorial Comment by John F. Bruzzi discussing this article. BACKGROUND. Lymphovascular invasion (LVI) is an adverse prognostic indicator in non–small cell lung cancer (NSCLC) and se...

Summary Cribriform Gleason pattern 4 (CGP4) is an indicator of poor prognosis in Gleason Score 7 prostate cancer; however, the significance of the size and percentage of this pattern and the presence of concomitant intraductal carcinoma (IDC) in these patients is unclear. To study the significance of these parameters in radical prostatectomy specimens, 165 cases with CGP4 were identified and reviewed (2017–2019). The size and percentage cribriform pattern and presence of IDC were noted and correlated with adverse pathological features and biochemical recurrence (BCR)-free survival. On review, 156 cases had CGP4 (Grade Group 2: 87 and Grade Group 3: 69). Large cribriform pattern and cribriform percentage of >20% showed significant association with extraprostatic extension, surgical margin positivity, and presence of IDC, whereas the presence of IDC was associated with all the analyzed adverse pathological features. BCR was seen in 22 of 111 (20%) patients after a median follow-up of 11 months, and of these, 21 had large cribriform pattern. On univariate analysis, all parameters had significant predictive values for BCR-free survival except for tertiary Gleason pattern 5. On multivariate analysis, while >20% cribriform pattern was trending to be an independent predictor, only lymphovascular invasion was statistically significant. Large cribriform pattern, >20% cribriform, and presence of IDC are additional pathologic parameters of potential value in identifying patients with high risk for early BCR.

Objective ndoscopic laryngopharyngeal surgery (ELPS) is a useful surgery for superficial cancers of the head and neck region, but it has not yet been well evaluated for synchronous multiple primary cancers (multiple primaries). The purpose of this study was to clarify the safety and usefulness of ELPS for patients with multiple superficial primary cancers in the head and neck region. Methods rom December 2009 to December 2016, 145patients with superficial head and neck cancers underwent ELPS. The patients were divided into two groups; a group consisting of patients with a single primary cancer (single primary) and another group consisting of patients with synchronous multiple primaries, and the incidences of postoperative complications and lymph node metastasis were retrospectively compared between the two groups. Results f the 145 patients, 107 had a single primary cancer and 38 had multiple primaries. There was no significant difference in the age, sex, or rate of intraepithelial cancer between the two groups. Postoperative complications included dysphagia in 6 (5.6%) patients with a single primary and 2 (5.3%) patients with multiple primaries. One patient with multiple primaries required gastrostomy because of aspiration pneumonia. In addition, the following complications were also observed. Laryngeal paralysis occurred in 2 (1.9%) patients with a single primary, and 1 (2.6%) patient with multiple primaries; tracheostomy because of postoperative bleeding in 1 (0.9%) patient with a single primary; infection occurred in 2 (5.3%) patients with multiple primaries. Postoperative lymph node metastasis was found in 7 (6.5%) patients with a single primary and 6 (15.8%) patients with multiple primaries. Lymphatic invasion of the primary cancer was noted in 3 (2.8%) patients with a single primary and 5 (13.2%) patients with multiple primaries, being significantly higher in the latter group. Conclusion ELPS is also a safe surgery for patients with multiple primaries. However, the incidence of lymphatic invasion of the primary cancer was significantly higher in patients with multiple primaries.

Lymphatic invasion (LI) is a potent risk factor for lymph node metastasis (LNM) in early gastric cancer (EGC) after endoscopic submucosal dissection (ESD). However, there are also other risk factors for LNM. Hence, to identify the need for additional surgery in some case of EGC without LI, the present study aimed to identify the risk factors for LNM in patients with EGC without LI.Data from 2284 patients diagnosed with EGC who underwent curative surgery at National Cancer Center in Korea from January 2012 to May 2019 were collected. The clinicopathological characteristics of patients with EGC without LI were compared on the basis of LNM status.There were 339 (17.1%) and 1648 (82.9%) patients with and without LI respectively. Among these patients with and without LI, 118 (34.8%) and 91 (5.5%) patients presented with LNM, respectively. In patients with EGC without LI, tumor size larger than 3 cm (OR = 2.12, 95% CI = 1.22-3.68; p = 0.007), submucosal invasion (OR = 4.14, 95% CI = 2.57-6.65; p 0.001), and undifferentiated histologic type (OR = 2.33, 95% CI = 1.45-3.76; p 0.001) were significant risk factors for LNM. Rates of LNM in patients meeting absolute, expanded, and beyond expanded criteria without LI were 0%, 1.5% (OR = 3.27, 95% CI = 0.18-59.41; p = 0.423), and 7.3% respectively. When the expanded criteria were divided into four subtypes patients with EGC, without LI within each subtype did not show significant risk of incidence of LNM compared to the absolute criteria.The current expanded criteria for endoscopic resection (ER) are tolerable in cases without LI, even though minimal risk LNM exists. Therefore, additional surgery may not be needed for patients meeting expanded criteria for ER.

Bladder carcinoma is the second most frequent cancer in Egyptian males. Leucine-rich and immunoglobulin-like domains (LRIGs) are usually dysregulated in various human tumors. The aim of this study is to explore the immunohistochemical expression of LRIG2 and LRIG3 in urothelial bladder carcinoma (UBC) and their relationship to patients clinicopathological data including survival. The study cohort included 79 UBC cases (14 non muscle invasive (NMI) and 65 muscle invasive (MI)). We assessed the associations of LRIG2 and LRIG3 expression with clinicopathological data, as well as progression-free and overall survival. Most of studied cases (>50%) express LRIG2 and LRIG3. Statistically significant association was observed between positivity for LRIG3 and muscle invasion (P = 0.001), high grade (P = 0.03), and female gender (P = 0.02). Moreover, positive LRIG2 staining was associated with early stage (T2) (P = 0.03), lymphovascular invasion (P = 0.004), and tendency to non-muscle invasive stage (P = 0.07). Grouping of cases according to positivity/negativity of both markers showed that cases with dual positivity for both proteins are associated with muscle invasion (P = 0.001) and paradoxically with prolonged overall survival (P = 0.037). We conclude that although the association of LRIG3 with MI and high-grade tumors, its expression is related to better survival. LRIG3 has the dominant role even if it coexists with LRIG2. The role of LRIG2 remains to be further investigated.

AIM Rectal neuroendocrine tumours (NETs) are the most common type of gastrointestinal NET. European Neuroendocrine Tumour Society guidelines suggest that rectal NETs measuring ≤10 mm are indolent with low risk of spread. In practice, many patients with lesions ≤1 cm do not undergo complete tumour staging. However, the size of the lesion may not be the only risk factor for nodal involvement/metastases. The aim of this study was to determine if MRI ± nuclear medicine imaging alters tumour stage in patients with rectal NETs ≤10 mm. METHODS Patients referred to a tertiary NET centre between 2005 and 2020 who met the inclusion criteria of a rectal NET ≤10 mm, full cross-sectional imaging, primarily an MRI scan and, if abnormal findings were identified, a subsequent 68 Ga-DOTATATE positron emission tomography scan were included. All patients were followed up at our institution. RESULTS In all, 32 patients with rectal NETs 10 mm or less were included in the study: 16 women; median age 58 years (range 33-71); 47% (n = 15) were referred from bowel cancer screening procedures. The median size of the lesions was 5 mm (range 2-10 mm). 81% (n = 26) were World Health Organization Grade 1 tumours with Ki67

Background. We developed a new nomogram combining serum biomarkers with clinicopathological features to improve the accuracy of prediction of nonsentinel lymph node (SLN) metastases in Chinese breast cancer patients. Methods. We enrolled 209 patients with breast cancer who underwent SLN biopsy and axillary lymph node dissection. We evaluated the relationships between non-SLN metastases and clinicopathologic features, as well as preoperative routine tests of blood indexes, tumor markers, and serum lipids, including lipoprotein a (Lp(a)). Risk factors for non-SLN metastases were identified by logistic regression analysis. The nomogram was created using the R program to predict the risk of non-SLN metastases in the training set. Receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in the validation set. Results. Lp(a) was significantly associated with non-SLN metastasis status. Compared with the MSKCC model, the predictive ability of our new nomogram that combined Lp(a) level and clinical variables (pathologic tumor size, lymphovascular invasion, multifocality, and positive/negative SLN numbers) was significantly greater (AUC: 0.732, 95% CI: 0.643–0.821) (C-index: 0.703, 95% CI: 0.656–0.791) in the training cohorts and also performed well in the validation cohorts (C-index: 0.773, 95% CI: 0.681–0.865). Moreover, the new nomogram with Lp(a) improved the accuracy (12.10%) of identification of patients with non-SLN metastases (NRI: 0.121; 95% CI: 0.081–0.202; P = 0.011 ). Conclusions. This novel nomogram based on preoperative serum indexes combined with clinicopathologic features facilitates accurate prediction of risk of non-SLN metastases in Chinese patients with breast cancer.

BACKGROUND In May 2018, the US Preventive Services Task Force (USPSTF) recommended prostate cancer (PCa) screening for ages 55-69 be an individual decision. This changed from the USPSTF's May 2012 recommendation against screening for all ages. The effects of the 2012 and 2018 updates on pathologic outcomes after prostatectomy are unclear. METHODS This study included 647 patients with PCa who underwent prostatectomy at our institution from 2005 to 2018. Patient groups were those diagnosed before the 2012 update (n = 179), between 2012 and 2018 updates (n = 417), and after the 2018 update (n = 51). We analyzed changes in the age of diagnosis, pathologic Gleason grade group (pGS), pathologic stage, lymphovascular invasion (LVI), and favorable/unfavorable pathology. Multivariable logistic regression adjusting for pre-biopsy covariables (age, prostate-specific antigen [PSA], African American race, family history) assessed impacts of 2012 and 2018 updates on pGS and pathologic stage. A p

Lymphovascular invasion (LVI) is a factor significantly impacting treatment and outcome of patients with gastric cancer (GC). We aimed to investigate prognostic aspects of a preoperative LVI prediction in GC using radiomics and deep transfer learning (DTL) from contrast-enhanced CT (CECT) imaging. A total of 1062 GC patients (728 training and 334 testing) between Jan 2014 and Dec 2018 undergoing gastrectomy were retrospectively included. Based on CECT imaging, we built two gastric imaging (GI) markers, GI-marker-1 from radiomics and GI-marker-2 from DTL features, to decode LVI status. We then integrated demographics, clinical data, GI markers, radiologic interpretation, and biopsies into a Gastric Cancer Risk (GRISK) model for predicting LVI. The performance of GRISK model was tested and applied to predict survival outcomes in GC patients. Furthermore, the prognosis between LVI (+) and LVI (−) patients was compared in chemotherapy and non-chemotherapy cohorts, respectively. GI-marker-1 and GI-marker-2 yield similar performance in predicting LVI in training and testing dataset. The GRISK model yields the diagnostic performance with AUC of 0.755 (95% CI 0.719–0.790) and 0.725 (95% CI 0.669–0.781) in training and testing dataset. Patients with LVI (+) trend toward lower progression-free survival (PFS) and overall survival (OS). The difference of prognosis between LVI (+) and LVI (−) was more noticeable in non-chemotherapy than that in chemotherapy group. Radiomics and deep transfer learning features on CECT demonstrate potential power for predicting LVI in GC patients. Prospective use of a GRISK model can help to optimize individualized treatment decisions and predict survival outcomes.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P

The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery. A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed. The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P

PURPOSE. Routine use of the Oncotype DX Recurrence Score (RS) in patients with early-stage, estrogen receptor-positive, HER2-negative (ER+/HER2−) breast cancer is limited internationally by cost and availability. We created a supervised machine learning model using clinicopathologic variables to predict RS risk category in patients aged over 50 years. METHODS. From January 2012–December 2018, we identified patients aged over 50 years with T1-2, ER+/HER2−, node-negative tumors. Clinicopathologic data and RS results were randomly split into training and validation cohorts. A random forest model with 500 trees was developed on the training cohort, using age, pathologic tumor size, histology, progesterone receptor (PR) expression, lymphovascular invasion (LVI), and grade as predictors. We predicted risk category (low: RS ≤25, high: RS >25) using the validation cohort. RESULTS. Of the 3880 tumors identified, 1293 tumors comprised the validation cohort in patients of median (IQR) age 62 years (56–68) with median (IQR) tumor size 1.2 cm (0.8–1.7). Most tumors were invasive ductal (80.3%) of low-intermediate grade (80.5%) without LVI (80.9%). PR expression was ≤20% in 27.3% of tumors. Specificity for identifying RS ≤25 was 96.3% (95% CI 95.0–97.4), and the negative predictive value was 92.9% (95% CI 91.2–94.4). Sensitivity and positive predictive value for predicting RS >25 was lower (48.3% and 65.1%, respectively). CONCLUSION. Our model was highly specific for identifying eligible patients aged over 50 years for whom chemotherapy can be omitted. Following external validation, it may be used to triage patients for RS testing, if predicted to be high risk, in resource-limited settings.

Background Lymph node metastasis (LNM) status is an important prognostic factor that strongly influences the treatment decision of early gastric cancer (EGC). This study aimed to evaluate the pattern and clinical significance of LNM in EGC. Methods A total of 354 patients with carcinoma in situ (n = 42), EGC (n = 312) who underwent radical gastrectomy were enrolled. Their clinicopathological features, pathological reports, and prognostic data were collected and analyzed. Results The incidence of LNM in all patients was 18.36% (65/354). The rates of D1 and D2 station metastases were 12.10% (43/354) and 6.21% (22/354), respectively. The rates of LNM in absolute indication of endoscopic resection and expanded indication were 3.27% (2/61) and 28.55% (4/14), respectively. Skip LNM was observed in 3.67% (13/354) of patients. For those with middle-third tumor, the metastasis rate of the No. 5 lymph node was 3.05% (5/164). The independent risk factors for LNM were tumors measuring > 30 mm, poorly differentiated tumors, and lymphovascular invasion (all P P = 0.011). Tumors measuring > 20 mm and LNM were independent predictive factors for poor survival outcome in all patients. Conclusions Patients with EGC conforming to expanded indications have a relatively high risk of LNM and may not be suitable for endoscopic submucosal dissection. Pylorus-preserving gastrectomy for patients with middle-third EGC remains controversial due to the high metastasis rate of the No. 5 lymph node.

Aim: This study aimed to investigate the correlation between the pathologic and ultrasound (US) characteristics of colon cancer and the heavy axillary nodal burden. Methods: In total, 631 patients diagnosed with invasive colon cancer were recruited with ethical ratification. Results: The unitary pathologic features correlated with heavy axillary lymph nodal burden included the age of patient (p = 0.035), tumor size (p = 0.001), lymph node metastasis (p = 0.001), lymphovascular invasion (p = 0.020) and pathology type (p = 0.012). The independent US characteristics correlated with heavy axillary nodal burden included posterior acoustic enhancement (p = 0.006). Heavy axillary nodal burden was correlated with tumor size, lymph node metastasis, lymphovascular invasion and pathology type. Conclusion: Tumor size, lymph node metastasis and posterior acoustic can be used to predict the axillary lymph node tumor burden.

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.

Background Lymphovascular invasion (VI) is an established prognostic marker for many cancers including bladder cancer. There is a paucity of data regarding whether the prognostic significance of lymphatic invasion (LVI) differs from blood vessel invasion (BVI). The aim was to examine LVI and BVI separately using immunohistochemistry (IHC), and investigate their associations with clinicopathological characteristics and prognosis. A secondary aim was to compare the use of IHC with assessing VI on standard HAS (hematoxylin-azophloxine-saffron) sections without IHC. Methods A retrospective, population –based series of 292 invasive bladder cancers treated with radical cystectomy (RC) with curative intent at Vestfold Hospital Trust, Norway were reviewed. Traditional histopathological markers and VI based on HAS sections were recorded. Dual staining using D2–40/CD31 antibodies was performed on one selected tumor block for each case. Results The frequency of LVI and BVI was 32 and 28%, respectively. BVI was associated with features such as higher pathological stages, positive regional lymph nodes, bladder neck involvement and metastatic disease whereas LVI showed weaker or no associations. Both BVI and LVI independently predicted regional lymph node metastases, LVI being the slightly stronger factor. BVI, not LVI predicted higher pathological stages. BVI showed reduced recurrence free (RFS) and disease specific (DSS) survival in uni-and multivariable analyses, whereas LVI did not. On HAS sections, VI was found in 31% of the cases. By IHC, 51% were positive, corresponding to a 64% increased sensitivity in detecting VI. VI assessed without IHC was significantly associated with RFS and DSS in univariable but not multivariable analysis. Conclusions Our findings indicate that BVI is strongly associated with more aggressive tumor features. BVI was an independent prognostic factor in contrast to LVI. Furthermore, IHC increases VI sensitivity compared to HAS.

Background/Aims: The treatment of gastric cancer remains unsatisfactory. We aimed to investigate the prognostic value of immunohistochemical staining in gastric cancer.Methods: We analyzed 505 (279 early staged, 226 advanced-staged) gastric cancer tissues from patients who underwent radical gastric resection between January 2014 and December 2016. Available surgical specimens immunohistochemically stained for p53, epidermal growth factor receptor (EGFR), human EGFR 2 (HER-2), E-cadherin, and Ki-67 were reviewed. We evaluated the association between positivity to various biomarkers and disease recurrence, disease-free survival, lymph node metastasis, and microscopic lymphovascular invasion.Results: The median follow-up duration was 32.5 months (range, 7 to 70). Advanced gastric cancer cases showed high Ki-67 expression; other cases showed unremarkable expression. Concerning disease recurrence, lymphatic invasion, and disease-free interval, all biomarkers had no prognostic effects. HER-2-positive stage I gastric cancer tended to occur in old patients and in the upper one-third of the stomach (p = 0.01). HER-2 positivity was significantly correlated with disease recurrence (p = 0.01), lymphatic invasion (p = 0.03), and vascular invasion (p = 0.03) in stage I cases.Conclusions: Only HER-2 was associated with the recurrence of stage I gastric cancer. HER-2-positive stage I gastric cancer requires additional therapy despite curative resection.

Background The clinicopathological predictors of sentinel lymph node (SLN) metastasis in clinical T1-T2 N0 (cT1-T2 N0) patients with a normal axillary ultrasound (AUS) are unclear. Purpose To assess the association between clinicopathological characteristics of a primary tumor and SLN metastasis in cT1-T2 N0 patients with a normal AUS. Material and Methods Patients who were diagnosed with cT1-T2 N0 invasive breast cancer and who obtained normal AUS results between October 2016 and September 2018 in a single hospital were included. Clinicopathological data were collected to explore the predictors of SLN metastasis using a multivariate logistic regression model. Results SLN metastasis occurred in 26 patients (18.4%) among 141 AUS-normal patients, of which 24 cases (17.0%) had one or two nodal involvements. In the univariate analysis, tumor location, estrogen receptor (ER) status, progesterone receptor (PR) status, and lymphovascular invasion (LVI) were significantly associated with SLN metastasis ( P Conclusion Tumor location in the upper outer quadrant, positive PR, and LVI status were found to be significantly high-risk factors for SLN metastasis among cT1-T2 N0 breast cancer patients with a normal AUS result.

Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer. Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for “normal” (

To compare the disease-free survival (DFS) and overall survival (OS) at 3 years and 5 years in patients undergoing treatment for early-stage cervical cancer with either robotic (RRH) or open radical hysterectomy (ORH). This retrospective study compared all patients with stage IA1 (lymphovascular invasion), IA2, IB1, IB2 and II A cervical cancer in accordance with International Federation of Gynaecology and Obstetrics staging (FIGO 2009) of cancer of the cervix uteri. Patients who underwent Radical Hysterectomy at our centre from January 2011 till January 2018 were included in the study. One hundred and eighty-nine patients ( ORH = 67, RRH = 122) were included. The median follow-up time was 46.3 months in RRH group and 70.0 months in the ORH group. The 3-year DFS was comparable in both the arms, 91.5% in RRH and 91.6% in ORH. The 5-year DFS was 88.9% and 85.9% in robotic and open approaches, respectively (P = 0.258), hazard ratio (HR) 0.616 (CI = 0.266-1.427). The 3-year overall survival for robotic approach was 93.4% and for open was 95%, whereas 5-year overall survival was 84.7% and 87.4% in robotic and open approaches, respectively (P = 0.813). The median estimated blood loss for robotics was lower (100 ml vs 300 ml, P

Dysregulation of epigenetic mechanisms, reflected by loss of expression of 5-hydroxymethylcytosine (5-hmC) is being increasingly recognized as a marker of aggressive behavior in several neoplasms; however, the role of such epigenetic modifiers in pancreatic neuroendocrine tumors (PanNETs) has not been studied. Annotated cohort of 60 PanNETs was evaluated for 5-hmC expression using immunohistochemistry. Univariable and multivariable analyses were performed. To determine intratumor heterogeneity of 5-hmC expression, 26 additional synchronous metastatic deposits of PanNETs from 8 patients were evaluated for 5-hmC expression. 5-hmC level showed significant association with the presence of distant metastases (P=0.02), female sex (P=0.04), and Ki-67 proliferation index (P=0.002). A multivariate model created using the stepwise logistic regression analysis showed the presence of nodal metastases (odds ratio=6.15), lymphovascular invasion (odds ratio=4.07) and lack of 5-hmC expression (odds ratio=5.34) were predictive of the risk of distant metastasis in PanNETs with a c-statistic of 0.845. Epigenetic intratumoral heterogeneity of 5-hmC expression was seen in 37.5% cases (3/8). Our work provides evidence that epigenetic regulators are involved in the pathobiology of PanNETs and immunohistochemical analysis of 5-hmC may be able to refine prognostic evaluation of these tumors.

Objectives/hypothesis Hashimoto's Thyroiditis (HT) is a common cause of hypothyroidism. Among adults with differentiated thyroid cancer (DTC), HT appears to be associated with less severe disease burden. In the absence of information regarding HT and disease burden among children with DTC, we assessed the relationship between pediatric DTC severity and HT. Study design Retrospective cohort. Methods Charts from 90 pediatric patients who underwent surgical removal of DTC from 2002 to 2017 at tertiary-care children's hospital were reviewed. Demographic, clinical, surgical, pathology, and outcome details were compared between patients with and without HT. Consistency among diagnostic modalities of HT was also evaluated. Results Median age at presentation was 16.0 years (range 4.2-18.9 years). Twenty-two patients were male (24%). Forty-five patients (50%) had HT based on presence of thyroid autoantibodies and/or surgical pathology findings and 45 patients did not have HT. Patients with HT had increased odds of microcalcifications (odds ratio [OR]: 3.01, P = .031) and decreased odds of palpable nodules (OR: 0.212, P = .024) and T2 lesions (vs. T1) (OR: 0.261, P = .015) compared with non-HT. No significant differences in demographics and the incidence of multifocality, extrathyroidal extension, lymphovascular invasion, lymph node or pulmonary metastases, disease recurrence, or radioactive iodine treatment were found between the two groups. Thyroglobulin/thyroid peroxidase autoantibodies and surgical pathology indicative of HT were concordant in 82.4% (κ = 0.635, P Conclusion HT was present in 50% of children with DTC. Patients with DTC and HT presented with smaller tumors compared to non-HT patients. No significant differences in other markers of disease aggressiveness were found between the two groups. Level of evidence 3 Laryngoscope, 2021.

OBJECTIVES Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. METHODS Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). RESULTS In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. CONCLUSIONS Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

BackgroundSince implementing the NHS bowel cancer screening programme, the rate of early colorectal cancer (eCRC; pT1) has increased threefold to 17%, but how these lesions should be managed is currently unclear.AimTo improve risk stratification of eCRC by developing reproducible quantitative markers to build a multivariate model to predict lymph node metastasis (LNM).MethodsOur retrospective cohort of 207 symptomatic pT1 eCRC was assessed for quantitative markers. Associations between categorical data and LNM were performed using χ2 test and Fisher’s exact test. Multivariable modelling was performed using logistic regression. Youden’s rule gave the cut-point for LNM.ResultsAll significant parameters in the univariate analysis were included in a multivariate model; tumour stroma (95% CI 2.3 to 41.0; p=0.002), area of submucosal invasion (95% CI 2.1 to 284.6; p=0.011), poor tumour differentiation (95% CI 2.0 to 358.3; p=0.003) and lymphatic invasion (95% CI 1.3 to 192.6; p=0.028) were predictive of LNM. Youden’s rule gave a cut-off of p>5%, capturing 18/19 LNM (94.7%) cases and leading to a resection recommendation for 34% of cases. The model that only included quantitative factors were also significant, capturing 17/19 LNM cases (90%) and leading to resection rate of 35% of cases (72/206).ConclusionsIn this study, we were able to reduce the potential resection rate of pT1 with the multivariate qualitative and/or quantitative model to 34% or 35% while detecting 95% or 90% of all LNM cases, respectively. While these findings need to be validated, this model could lead to a reduction of the major resection rate in eCRC.

Introduction Tumor size is an absolute recurrence risk in lung cancer. Although morphological features also reflect recurrence risk, its significance among lower‐risk cases characterized by small size is unknown. We aimed to evaluate the relationship between pathological invasive tumor size and morphological features, and their prognostic impact by considering them simultaneously in lung adenocarcinoma. Patients and methods We retrospectively reviewed 563 pN0M0 patients with pathological invasive size of ≤40 mm. The patients were classified by pathological invasive size and pathological malignant grading using the proportion of subhistological components. The prognostic impact was evaluated using recurrence‐free survival (RFS) and overall survival (OS). The impact on prognosis was evaluated using uni‐ and multivariate analyses. Results The proportion of histological grade changed according to invasive tumor size. Patients with high malignant grade (G3) showed worse RFS than those with low and intermediate malignant grade (G1+2) with invasive size ≤20 mm. The 5‐year RFS (G1+2 vs. G3) in 5–10 mm was 96.0% vs. 83.3% (HR = 5.505, 95% CI = 7.156–1850, p, Invasive tumor size and pathological malignant grade overlap in invasive adenocarcinoma. Distribution of the 576 patients according to invasive tumor size and pathological malignant grading. A total of 563 patients (surrounded by red squares) were evaluated (a). Bar graph indicating the percentage of each pathological grade according to invasive tumor size (b).

Background Mitotic rate is one of the major prognostic factors in melanoma. Objective To investigate the significance of mitotic rate and possible impacts of clinicopathological factors on the course of all staged melanoma patients. Methods A total number of 970 melanoma patients were analyzed. Mitotic rates were grouped for analysis as follows: 0-1, 1.1-4.9, 5-9.9, and ≥10 mitoses/mm2 . Results Melanomas with higher mitotic rates were more likely to be associated with nodular histology (P = 0.0001), higher Clark level (P = 0.0001), thick Breslow depth (P = 0.0001), ulceration (P = 0.0001), vertical growth pattern (P = 0.0001), neurotropism (P = 0.04), lymphovascular invasion (P = 0.01), de novo melanoma (P = 0.0001), absence of tumor infiltrating lymphocytes (P = 0.02), advanced stage (P = 0.0001), and relapse (P = 0.0001). The 5-year overall survival (OS) rate of all patients was 68.7%, and it decreased significantly from 87% in melanomas with 0-1 mitoses/mm2 to 65.2%, 56.6%, and 50.4% in melanomas with 1.1-4.9, 5-9.9, and ≥10 mitoses/mm2 , respectively (P = 0.0001). Age (P = 0.04), gender (P = 0.03), histology (P = 0.0001), Clark level (P = 0.001), T-stage (P = 0.003), ulceration (0.006), node involvement (P = 0.0001), metastasis (P = 0.005), and relapse (P = 0.0001) were correlated with OS in 0-1 mitoses/mm2 melanomas, whereas lymphovascular invasion (P = 0.0001), BRAF mutation (P = 0.01), metastasis (P = 0.0001), relapse (P = 0.0001), and relapse pattern (P = 0.005) were found significant for ≥10 mitoses/mm2 melanomas. Conclusion Higher tumor mitotic rates associated with known histopathological and clinical poor prognostic factors were found to be significantly independent predictors of early relapse and unfavorable survival for cutaneous melanoma patients. Moreover, different prognostic variables were found to be affecting survivals in melanoma patients with lower and higher mitosis.

BACKGROUND Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery. METHODS A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into 'responders' (Mandard grade 1-3) and 'non-responders' (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated. RESULTS Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02-3.62; p = 0.05), a 'partial response' RECIST score (OR 7.16 95%CI 1.49-34.36; p = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05-7.04; p = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02-0.13; p = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86. CONCLUSION This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.

Breast cancer (BC) is the second most frequent type of cancer for both sexes combined, after lung cancer. Triple-negative BC (TNBC) molecular subtype is characterized by lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) immunoexpression or amplification and represent 10–20% of all BC cases. The issue of the present study was to analyze the associations between programmed death-ligand 1 (PD-L1) immunoexpression and distribution of stromal tumor-infiltrating lymphocytes (stTILs) combined with clinico-morphological features of patients with TNBC. Secondly, our research evaluated PD-L1 immunoexpression as a prognostic factor and its correlation with p53 immunoexpression. Thirty cases with primary TNBC without prior neoadjuvant therapy were included in this research. stTILs were identified in all cases, most of them with low distribution (66.7%). A positive immunoreaction for PD-L1 was observed in 40% of cases. The PD-L1 immunoexpression was statistically significant associated with age, pathological tumor size, lymphovascular invasion, stTILs level, the presence of cluster of differentiation 8-positive (CD8+) TILs and p53 immunoexpression. In the present study, a positive PD-L1 immunoexpression was associated with a worse distant metastasis free survival (DMFS). We also found not only that high stTILs level were associated with a better DMFS but also that there was a statistically significant association between stTILs level and PD-L1 immunoexpression. Our results bring new insights to the fine connections between tumor microenvironment and molecular changes of TNBC. It helps us to better understand these aggressive tumors to identify the more useful biomarkers for predicting the response to adjuvant therapy and can represent a method for selecting the most suitable patients for immunotherapy.

As endoscopic approaches become more widely used to treat early-stage esophageal cancer, reliably identifying patients with less-aggressive tumors is paramount. We sought to identify risk factors for recurrence in patients with completely resected T1 esophageal adenocarcinoma.We retrospectively analyzed a single-institutional database for all patients with completely resected pathologic T1 esophageal adenocarcinoma (1996-2016). Risk factors for recurrence were identified using competing-risk regression methods. Risk stratification was performed on the basis of known preoperative clinicopathologic factors; this model's discriminative power for overall survival was evaluated using a Cox proportional hazards model.Of 243 patients, 32 experienced recurrence. At a median follow-up among survivors of 4 years (range, 0.05-19 years), the 5-year cumulative incidence of recurrence was 15%, and median time to recurrence was 2 years (range, 0.26-6.13 years). On univariable analysis, submucosal invasion, N1 disease, poor differentiation, tumor length, lymphovascular invasion, and multicentricity were significantly associated with recurrence. On multivariable analysis, N1 disease (hazard ratio, 2.93; 95% confidence interval, 1.17-7.34; P = .022) and tumor length (hazard ratio, 1.44; 95% confidence interval, 1.12-1.86; P = .004) were independently associated with recurrence. Risk stratification showed that patients without lymphovascular invasion and a with median tumor length of 0.8 cm (range, 0.10-1.70 cm) had a10% risk of recurrence and improved survival.Pathologic T1 tumors have a 5-year cumulative incidence of recurrence of 15%. Nodal involvement and tumor length were independent risk factors for recurrence, whereas tumors2 cm in length without lymphovascular invasion were associated with a low risk of recurrence.

Background There are no series evaluating penile squamous cell carcinoma (pSCC) based on human papillomavirus (HPV) infection. Herein, we present national registry data on clinical and survival outcomes for pSCC based on HPV status. Methods We performed a retrospective review of 1224 pSCC patients with known HPV staining from the National Cancer Database. Patients with cM1 disease, those who did not receive treatment, or had missing follow‐up data were excluded. Logistic regression identified factors associated with locally aggressive disease. Univariable, multivariable, and inverse probability of treatment weighting (IPTW)‐Cox proportional hazard modeling were used to assess hazard ratios (HR) associated with overall survival (OS). Results After exclusion criteria, we identified 825 cases of which 321 (38.9%) were HPV positive. The HPV‐positivity rate did not significantly change by year. HPV‐positive patients were younger, had lower Charlson‐Deyo performance score, and resided in areas with both lower median household income and lower school education completion. HPV‐positive tumors presented with lower American Joint Committee on Cancer clinical T‐stage (cT), poorer differentiation, lower rates of lymphovascular invasion (LVI), but more node‐positive disease (cN+). For those who underwent lymph node surgery, there were no differences in final pathologic stage, upstaging, or presence of extranodal extension. Only tumor differentiation, LVI, and performance score were independent predictors for locally aggressive disease. HPV status was not a predictor of OS (IPTW‐HR:0.89, p = 0.13). Conclusions In the largest series evaluating pSCC based on HPV status, HPV‐positive tumors were associated with lower cT stages, less LVI, but more cN + disease. More studies on prognostic factors are needed, and time may still be immature to use HPV information for risk stratification., Infection with human papillomavirus (HPV) is endemic and a causative agent for several malignancies in both male and female populations. In this study, we queried a large, cancer registry to look for clinical and survival differences between HPV‐positive versus negative penile tumors. Our results noted a lack of prognostic impact for HPV‐derived tumors, although more studies will be required to validate results.

Methods We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p, Final tumor grading of oral cavity squamous cell carcinoma (OCSCC) is assigned according to the most prevalent grade. Relapses of poorly differentiated OCSCC tended to occur regionally and distantly. Poor tumor differentiation was the second most relevant adverse risk factor after extranodal extension. The NCCN guidelines should include poor differentiation as an adverse risk factor.

The rising incidence of thyroid cancer has been attributed to increased detection of papillary thyroid microcarcinoma (PTMC). Although some PTMCs are thought to harbor aggressive pathologic features, the clinical significance of these features remains unclear. This study examines factors associated with survival in this patient population.Adults with PTMC, defined as papillary thyroid carcinoma ≤ 1.0 cm, who underwent thyroidectomy between 2004 and 2016, were identified in the National Cancer Database. Demographic and clinical variables were analyzed. The primary aim was to identify factors associated with survival. The secondary aim was to assess the association of microscopic margins on survival and to identify factors associated with margin positivity. Overall survival was estimated using Kaplan-Meier methods and compared using log rank tests. Cox proportional hazards and binary logistic regression models identified factors associated with survival and margin positivity, respectively.Of 77,817 patients with PTMC, 13,507 met inclusion criteria; 2,649 (20%) of these patients presented with advanced features: extrathyroidal extension (n = 916, 7%), lymphovascular invasion (n = 398, 3%), lymph node involvement (n = 2,003, 15%), and distant metastasis (n = 39,1%). Microscopic margin positivity was present in 906 patients and associated with increased risk of death (hazard ratio 1.58, 95% CI 1.04-2.41). Academic facilities (odds ratio [OR] 0.75, 95% CI 0.59-0.95) and operative volume (OR 0.98, 95% CI 0.97-0.98) were associated with decreased margin positivity.Positive margin status was significantly associated with increased risk of death for PTMC. Higher operative volume and treatment at academic centers were associated with lower rates of margin positivity and may help improve survival outcomes in PTMC patients with aggressive features.

In 2020, the WHO published a new system for classifying invasive endocervical adenocarcinoma based on histological features and high-risk human papillomavirus (HPV) infection. However, immunophenotypes of each histological subtype require further investigation. We immunohistochemically analyzed 66 invasive endocervical adenocarcinomas using three cell-lineage–specific markers: claudin 18 (CLDN18) for gastric, cadherin 17 (CDH17) for intestinal, and PAX8 for Mullerian epithelial cells. We identified five immunophenotypes of endocervical adenocarcinoma: gastric (21%); intestinal (14%); gastrointestinal (11%); Mullerian (35%); and not otherwise specified (NOS) (20%). Adenocarcinomas with gastric immunophenotype, characterized by aging (p = 0.0050), infrequent HPV infection (p