Positive Lymphovascular Invasion Research Articles

Simultaneous Endometrial Cancer with Extensive Pelvic and Vulvar Endometriosis: A Case Report

Background: Endometrial cancer represents the most prevalent malignant genital tract neoplasm in high-income countries and is the second most common cancer worldwide following cervical cancer. Endometriosis is a benign condition wherein endometrial glands and stroma are found outside the uterine cavity. Case Presentation: During a routine care and ultrasound examination of the uterus and adnexa of a 64-year-old woman, an increased endometrial thickness (22 mm) was noted. In 2023, according to ultrasound report, the patient underwent diagnostic curettage with immunohistochemistry, revealing a pathological diagnosis of endometrial cancer (endometrioid adenocarcinoma) with positive staining for p16, estrogen receptor (ER), and vimentin. Subsequently, after one week, she underwent complete surgical staging. Extensive superficial endometriosis disseminated in the pelvis and vulva was noted during surgery and preoperative examinations. Final pathology confirmed a well-differentiated typical endometrioid carcinoma (grade 1) with 40% myometrial invasion and positive lymphovascular invasion. The patient was considered to be at stage 1A. Conclusion: Despite some studies suggesting an unclear association between endometriosis and endometrioid or clear-cell ovarian cancers, the correlation between endometriosis and endometrial cancer and its prognosis remains ambiguous. Additionally, although infertility has been linked to both endometrial cancer and endometriosis in various studies, the presented case exhibited no signs of infertility. Extensive pelvic endometriosis with vulvar involvement was present, yet the patient did not exhibit any symptoms. This is in contrast to the typical initial manifestation of endometrial cancer, which is abnormal uterine bleeding. The patient's condition was incidentally detected through routine care due to an abnormal increase in endometrial thickness, prompting this presentation.

A nomogram to predict the risk of axillary upstaging in patients with Z0011-eligible breast cancer.

e12606 Background: ACOSOG Z0011 trial showed that in early cT1-2N0 breast cancer patients with 1-2 positive lymph nodes in sentinel lymph node biopsy (SLNB) can safely omit axillary lymph node dissection (ALND) without compromising local control and long-term survival. Although it is widely accepted worldwide, controversy and concerns remain that the incidence of non-sentinel lymph node metastasis may lead to pathological lymph node (pN) upstaging and insufficient systemic treatment. This study aims to identify risk factors for having ≥4 metastatic lymph node (pN2-3) in patients who met Z0011 criteria and received SLNB. Methods: This is a retrospective study enrolled 733 cT1-2N0 breast cancer patients with 1-2 positive SLNs treated between 2011-2022 at Sun Yat-sen Memorial Hospital. All patients had received SLNB followed by ALND. Patients included were divided into the training and validation sets at a 7:3 ratio. Differences were compared between pN1(1-3 LN+) and pN2-3(≥4 LN+) in training set using either t test or chi-squared test. Multivariate logistic regression was conducted to identify risk factors for pN upstaging and to form the basis of a predictive nomogram. The validation was processed in the other validation set and nomogram performance was evaluated using the area under ROC curve (AUC). Results: Among the 733 patients enrolled, 127 (17.3%) patients had pN upstaging (pN2-3) after ALND. There was a big difference of pN upstaging between the patients with 1 (47/511, 9.2%) and 2 (80/222, 36%) positive SLNs. 488 patients were allocated to the training set, among which 18.2% had pN upstaging. In univariate analysis, pN were differed by cT stage, axillary ultrasound appearance, histological grade, molecular subtype, Ki67, lymph vascular invasion, pathological tumor size, SLN metastasis type (micrometastasis or macrometastasis), positive SLN numbers and negative SLN numbers. Multivariate logistic analysis resulted six independent risk factors associated to pN upstaging: ultrasound suspicious node (OR=1.93; 95% CI: 1.08-3.47), positive lympho-vascular invasion (OR=2.27; 95% CI: 1.25-4.13), larger tumor size (OR=2.07; 95% CI: 1.15-3.73), SLN macro-metastasis (OR= 9.15; 95% CI: 1.07-78.13), two positive SLNs (OR= 6.59; 95% CI:3.70-11.76) and less negative SLN number (OR=1.54; 95% CI: 1.22-1.89). These factors were used to construct a predictive nomogram, exhibiting excellent performance with AUC values of 0.819 and 0.827 in the training and validation cohorts respectively. Conclusions: The Z0011-eligible patients with two positive SLNs may have a high risk of pN upstaging and need to be cautious to spare ALND. A practical nomogram is helpful to identify patients at high risk of pN upstaging and avoid insufficient systemic treatment.

Clinical outcomes of colorectal neoplasm with positive resection margin after endoscopic submucosal dissection

A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

The Discovery of Oral Cancer Prognostic Factor Ranking Using Association Rule Mining.

A 5-year survival rate is a predictor for the assessment of oral cancer prognosis. The purpose of this study is to analyze oral cancer data to discover and rank the prognostic factors associated with oral cancer 5-year survival using the association rule mining (ARM) technique. This study is a retrospective analysis of 897 oral cancer patients from a regional cancer center between 2011 and 2017. The 5-year survival rate was assessed. The multivariable Cox proportional hazards analysis was performed to determine prognostic factors. ARM was applied to clinicopathologic and treatment modalities data to identify and rank the prognostic factors associated with oral cancer 5-year survival. The 5-year overall survival rate was 35.1%. Multivariable Cox proportional hazards analysis showed that tumor (T) stage, lymph node metastasis, surgical margin, extranodal extension, recurrence, and distant metastasis of tumor were significantly associated with overall survival rate (p < 0.05). The top associated death within 5 years rule was positive extranodal extension, followed by positive perineural and lymphovascular invasion, with confidence levels of 0.808, 0.808, and 0.804, respectively. This study has shown that extranodal extension, and perineural and lymphovascular invasion were the top ranking and major deadly prognostic factors affecting the 5-year survival of oral cancer.

Abstract PO1-07-11: Radiogenomic-based imaging intratumor heterogeneity model predicts breast cancer prognosis and unveils therapeutic targets

Abstract Background: Intratumor heterogeneity (ITH) refers to variations observed among cancer cells within a single tumor, posing significant challenges in clinical practice due to its contribution to treatment resistance and unfavorable outcome. However, the inconvenience of multi-region biopsy and limitations of genomic sequencing based on limited tissue impede the practical detection of ITH. Consequently, there is an urgent need for a non-invasive method that comprehensively captures ITH from a holistic perspective of the entire tumor. Methods: We utilized a large multicenter dataset comprising dynamic contrast-enhanced magnetic resonance images from breast cancer patients (n = 1423) along with matched multiomics data (n = 468) to develop a non-invasive machine learning approach for measuring ITH. We extracted quantitative radiomic features from both the entire tumor and peritumor regions, with a specific focus on features associated with imaging heterogeneity. Using these radiomic features, we established an imaging ITH (IITH) model. The robustness of IITH evaluation was determined by assessing its correlation with genomic ITH (employing the mutant-allele tumor heterogeneity [MATH] algorithm) and pathological cellular ITH (analyzing variation in quantitative nuclear features extracted through digital pathology). Prognostic power was evaluated using Kaplan-Meier and multivariate Cox proportional hazards analyses. Integrated multiomics analyses were performed to investigate the molecular basis of different IITH subgroups. Results: We developed a non-invasive radiomic signature to quantify imaging ITH (IITH) in the FUSCC cohort. Breast cancer patients were retrospectively categorized into high and low IITH groups. Multivariate Cox analysis identified high IITH as an independent predictor of poor prognosis in breast cancer patients, even after adjusting for clinical risk factors such as tumor size, positive lymph nodes, clinical subtype and lymphovascular invasion status. These findings were further validated in the DUKE cohort, confirming the prognostic value of IITH. Moreover, we substantiated the robustness of IITH by demonstrating its association with genomic and pathological ITH. Multiomics analysis revealed the activation of oncogenic pathways and metabolic dysregulation in high-IITH tumors. Intriguingly, our investigation also highlighted ferroptosis as a vulnerability and potential therapeutic target in high-IITH tumors, which was further supported by evidence from the TCGA cohort. Conclusion: Radiomic-based assessment of ITH provides a non-invasive approach to comprehensively capture ITH and predict the prognosis of breast cancer patients. Targeting ferroptosis may hold promise as a treatment strategy for patients with high IITH. Citation Format: Guan-Hua Su, Yi Xiao, Chao You, Ren-Cheng Zheng, Shen Zhao, He Wang, Yi-Zhou Jiang, Ya-Jia Gu, Zhi-Ming Shao. Radiogenomic-based imaging intratumor heterogeneity model predicts breast cancer prognosis and unveils therapeutic targets [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-11.

Association of adjuvant radiation and survival in human papilloma virus-positive oropharynx squamous cell carcinoma with lymphovascular invasion as the sole adverse pathologic feature.

Postoperative radiotherapy radiation therapy (PORT) for early-stage human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) with positive lymphovascular invasion (LVI) has an unclear association with overall survival (OS). This retrospective cohort study queried the National Cancer Database for surgically treated, T1-2, N0-1 HPV+ OPSCC from 2010 to 2019. Primary exposures were LVI and PORT, and the main outcome was 5-year OS. Odds ratios and hazard ratios (HR) with 95% confidence intervals (CIs) were generated using multivariable models and Cox proportional hazard models, respectively. Of 2768 patients, average age was 59.3 years, 2207 (79.7%) were male, and 386 (13.9%) had LVI. Of patients with LVI as their sole adverse pathologic feature, 220 (57.0%) received PORT, which was not associated with 5-year OS (HR, 1.13; CI, 0.65-1.19). Patients with surgically treated, early-stage HPV+ OPSCC and positive LVI as their only pathologic adverse feature may not require PORT.

Nomograms and prognosis for superficial esophageal squamous cell carcinoma

In recent years, endoscopic resection, particularly endoscopic submucosal dissection, has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma (ESCC). In this evolving paradigm, it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes. Larger tumor size, deeper invasion, poorer differentiation, more infiltrative growth patterns (INF-c), higher-grade tumor budding, positive lymphovascular invasion, and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews, leading to the construction of comprehensive nomograms for outcome prediction. If validated by future prospective studies, these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. The median follow-up period was 28.0months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

Significance of Serum Lactate Dehydrogenase as a Prognostic Marker and Outcome Predictor in Patients With Breast Cancer.

Background Breast carcinoma has been the most prevalent cancer in women, with research-based evidence showing a significant rise in the incidence of cancer and related morbidity and mortality in the Indian subcontinent. The predictive value of plasmatic lactate dehydrogenase (LDH) levels has been studied in breast cancer. Numerous studies have connected high LDH values to a poor prognosis, increased risk of incidence, recurrence, and associated mortality in patients with breast carcinoma. This study aimed to assess the clinical profile of breast carcinoma and determine the correlation of serum lactate dehydrogenase levels with the stage of the disease and assessment of high-risk features using histopathology and immunohistochemistry. Methods A total of 75 patients with carcinoma breast were enrolled for this study and classified into two groups: upfront surgery and post-adjuvant therapy. Serum LDH levels were estimated a day before the surgery (baseline) and on postoperative days 1, 7, 14, and 30. The clinical tumor, node, metastasis (cTNM) staging was correlated with pathological tumor, node, metastasis TNM (pTNM) staging and immunohistochemistry findings. Results The clinical characteristics of breast cancer, serum LDH levels, and stage of the disease were collected and analyzed. A significant decreasing trend was noted in LDH values post-op days, and statistically significant higher LDH values were noted in the triple-negative group, positive lymph nodes, and positive lymphovascular invasion patients. Conclusion Regularly elevated levels or an unanticipated rise in serum LDH might indicate poor outcomes. Hence, this non-specific enzyme marker can be suggested to be used routinely to assess disease outcomes.

Pathological characteristics predicting sentinel lymph node metastasis in early breast cancer patients.

In this study, we aimed to identify the predicting pathological factors affecting sentinel lymph node biopsy (SLNB) in patients with clinically node-negative breast cancer. Our single institution retrospective study was conducted at the Cancer Research Center of Shahid Beheshti University of Medical Sciences from 2018 to 2021. Data were imported into and analyzed using SPSS Version 28 for Windows (IBM Corp., Armonk, NY, USA). Of the 76 patients who underwent SLNB, 43 (56.6%) had negative SLNB and 33 (43.4%) had positive SLNB which led to axillary lymph node dissection (ALND). The relationship between hormone receptor status (ER/PR/Her2), pathology type (IDC, ILC, DCIS, LCIS), tumor size, and Ki67 expression was assessed. According to the results, axillary lymph node involvement can be predicted based on the scores and results of the three variables: IDC tumor type, lympho vascular invasion (LVI), and Ki67 expression. The positive relationship between IDC tumor type and LVI with SLNB indicates that with positive IDC tumor type and LVI, there is a higher probability of positive axillary lymph nodes (3.88 times higher probability for IDC tumor type and 6.75 times higher probability for the LVI factor). However, when the Ki67 expression is lower, the probability of positive axillary lymph nodes is higher (3.58 times higher probability). IDC tumor type, LVI, and lower Ki67 expression are independent predictive factors of positive SLNB.

The Impact of Waiting Time-to-Surgery on Survival in Endometrial Cancer Patients.

Endometrial cancer (EC) is the most common gynecological cancer in developed countries and a standard treatment of surgery should be performed as expediently as possible. Delay time to surgery and survival was debated. The aim of this investigation was to evaluate the effect of time-interval between diagnosis and surgery (TDS) in EC patients with regards to prognosis and mortality rates. This retrospective study was conducted between January 2009 and May 2021 at Bhumibol Adulyadej Hospital, Thailand. Subjects were EC cases who underwent primary surgery during the study period. Cases with partial treatment were disqualified from the study. Subjects who underwent surgery before and after 6 weeks were classified as early and delayed surgery groups. Baseline and clinical characteristics were collected and analyzed. During the study period, 419 EC cases were recruited. The mean age of participants was 56.8 years. Two-thirds (338/491) of subjects were menopausal. Endometrioid histology (406/491) was the most common histology subtype. Five years disease free survival (DFS) of early and delayed surgery groups were comparable at a percentage of 82.5 and 83.0, respectively. Among advanced stage and non-endometrioid EC cases, the delayed surgery group had significantly shorter DFS than the early group. Advanced stage, high grade and positive lympho-vascular space invasion (LVSI) were independent factors for poor DFS. Predictive factors for mortality were advanced stage and tumor recurrence. The TDS was not a prognostic factor for disease recurrence or overall mortality. Time to surgery equal to or more than 6 weeks gave worse prognosis for DFS among advanced stage or non-endometrioid histology EC.

Preoperative Dynamic Contrast-Enhanced and Diffusion-Weighted Breast Magnetic Resonance Imaging Findings for Prediction of Lymphovascular Invasion of the Lesions in Node-Negative Invasive Breast Cancer.

Purpose: Our single-centre retrospective study aimed to investigate the relationship between preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) findings and apparent diffusion coefficient (ADC) values and lymphovascular invasion (LVI) status of the lesions in patients with clinically-radiologically lymph node-negative invasive breast cancer. Methods: A total of 250 breast lesions diagnosed in preoperative magnetic resonance imaging were identified. All patients were divided into 2 subgroups: LVI-negative and LVI-positive according to the pathological findings of surgical specimens. The 2 groups' DCE-MRI findings, ADC values, and histopathological results of lesions were compared. Results: LVI was detected in 100 of 250 lesions. Younger age than 45 years and larger lesion size than 20 mm were found to be associated with the presence of LVI (P < .001). High histological and nuclear grade (P = .001), HER2-enriched molecular subtype (P = .001), and Ki-67 positivity (P = .016) were significantly associated with LVI. The LVI positivity rate was significantly higher in the lesions with medium-rapid initial phase kinetic curve and washout delayed phase kinetic curve (P = .001). The presence of LVI was significantly associated with the presence of peritumoural edema, sentinel lymph node metastasis, adjacent vessel sign, and increased whole breast vascularity (P < .001). When diffusion-weighted imaging findings were evaluated, it was determined that tumoural ADC values lower than 1068 × 10-6 mm2/second (P = .002) and peritumoural-tumoural ADC ratios higher than 1.5 (P = .001) statistically increased the probability of LVI. Conclusion: The patient's age, various histopathological and DCE-MRI findings, tumoural ADC value, and peritumoural-tumoural ADC ratio may be useful in the preoperative prediction of LVI status in breast cancer lesions.

Salvage Treatment of Recurrent or Persistent Anal Squamous Cell Carcinoma: The Role of Multi-modality Therapy

BackgroundThe standard treatment for recurrent or persistent anal squamous cell carcinoma is surgical salvage, but disease control and survival are suboptimal. Patients/MethodsPatients treated for recurrent or persistent anal squamous cell carcinoma at our institution from 2002 to 2022 were included. Patients were classified by type of salvage treatment received: surgery alone vs. reirradiation followed by surgery and by whether they received intraoperative radiation at the time of surgery. Clinical and pathologic variables were collected and assessed for association with risk of second local recurrence and death from any cause. ResultsSixty four patients were included; 55(85.9%) were treated with surgery alone and 9 (14.1%) were treated with reirradiation followed by surgery. Median (IQR) follow up from the time of salvage treatment was 40.0 (20.3-68.0) months. The 3-year cumulative incidence of second local recurrence (95% CI) after salvage surgery was 36% (24%-48%); 39% (26%-52%) for patients treated with surgery alone and 15% (0.46%-51%) for patients treated with reirradiation followed by surgery. Factors associated with increased second local recurrence after salvage surgery included a locoregional recurrence, lymphovascular space invasion and positive surgical margins. The 3-year overall survival (95% CI) after salvage surgery was 70% (59%-83%); 68% (7%-56%) after surgery alone and 89% (10.5%-70.6%) after reirradiation followed by surgery. Factors associated with worse overall survival included male sex, a larger recurrent tumor and positive surgical margins. ConclusionsApproximately 60% of patients achieved pelvic control after salvage therapy for recurrent or persistent anal squamous cell carcinoma. Although receipt of reirradiation and intraoperative radiation were not associated with improved second local recurrence or overall survival in our cohort, patients with positive surgical margins and lymphovascular space invasion on surgical pathology had higher rates of pelvic recurrence after salvage surgery and may benefit from escalated salvage therapy.

Immunohistochemical Evaluation of Perlecan (Heparan Sulphate Proteoglycan 2) Expression in Invasive Female Breast Carcinoma.

Breast cancer (BC) is the commonest type of female cancer worldwide and a leading cause of cancer-related deaths. Perlecan expression increases in aggressive breast cancers, pointing to a possible significance of this novel target therapy. Consequently, the current research investigates the immunohistochemical expression of Perlecan by tumor cells in female breast cancer and the correlation of such expression with the pathologic parameters of the tumors. A retrospective cross-sectional investigation was carried out. Seventy-four formalin-fixed, paraffin-embedded breast carcinoma tissue samples from patients undergoing modified radical mastectomy (MRM) or conservative breast surgery (CBS) were collected from the pathology department at Kasr El Aini Hospital. The paraffin blocks were sectioned and immunostained with Perlecan, and their expression was investigated in tumor cells and evaluated according to the H-score and classified into low and high expression. The expression was statistically correlated with the clinicopathological parameters of the cases. Perlecan expression was low in 41 cases (55.4%) and high in 33 cases (44.6%). It showed a statistically insignificant correlation with all studied parameters, but increased Perlecan expression was directly associated with poor tumor prognostic factors including higher tumor grade, advanced T stage, N3 stage, advanced anatomic stage, high Ki-67 index, positive lymphovascular invasion and perineural invasion, luminal B molecular subtype, and HER2 over-expression. Perlecan expression measured by immunohistochemical staining is associated with aggressive characteristics in breast cancer, suggesting that Perlecan may help in cancer progression and can be investigated as a possible target therapy.

Nodal Metastasis in Surgically Treated Oral Cavity Squamous Cell Carcinoma

Introduction: Management of the neck in oral cavity squamous cell carcinoma (OCSCC) is essential to oncologic control and survival. The rates of lymph node metastasis (LNM) vary based on oral cavity tumor site and stage and influence treatment decisions. The aim of this paper was to describe clinical LNM for different tumor subsites and stages of surgically managed OCSCC. Methods: We conducted a retrospective analysis of 25,846 surgically managed OCSCC patients from the National Cancer Database (NCDB) stratified by tumor subsite and clinical T-stage. For cN + patients, rates of pathologic LNM and absence of pathologic LNM were determined. For cN0 patients, outcomes included the rates of elective neck dissection (END) and occult LNM and predictors of occult LNM determined by a multivariable logistic regression model. Results: A total of 25,846 patients (59.1% male, mean age 61.9 years) met inclusion criteria with primary tumor sites including oral tongue (50.8%), floor of mouth (21.2%), lower alveolus (7.6%), buccal mucosa (6.7%), retromolar area (4.9%), upper alveolus (3.6%), hard palate (2.7%), and mucosal lip (2.5%). Among all sites, clinical N+ rates increased with T-stage (8.9% T1, 28.0% T2, 51.6% T3, 52.5% T4); these trends were preserved across subsites. Among patients with cN + disease, the overall rate of concordant positive pathologic LNM was 80.1% and the rate of discordant negative pathologic LNM was 19.6%, which varied based on tumor site and stage. In the overall cohort of cN0 patients, 59.9% received END, and the percentage of patients receiving END increased with higher tumor stage. Occult LNM among those cN0 was found in 25.1% of END cases, with the highest rates in retromolar (28.8%) and oral tongue (27.5%) tumors. Multivariable regression demonstrated significantly increased rates of occult LNM for higher T stage (T2 OR: 2.1 [1.9–2.4]; T3 OR: 3.0 [2.5–3.7]; T4 OR: 2.7 [2.2–3.2]), positive margins (OR: 1.4 [1.2–1.7]), and positive lymphovascular invasion (OR: 5.1 [4.4–5.8]). Conclusions: Management of the neck in OCSCC should be tailored based on primary tumor factors and considered for early-stage tumors.

Association between SMAD4 Mutations and GATA6 Expression in Paired Pancreatic Ductal Adenocarcinoma Tumor Specimens: Data from Two Independent Molecularly-Characterized Cohorts.

Several molecular biomarkers have been identified to guide induction treatment selection for localized pancreatic ductal adenocarcinoma (PDAC). SMAD4 alterations and low GATA6 expression/modified "Moffitt" basal-like phenotype have each been associated with inferior survival uniquely for patients receiving 5-FU-based therapies. SMAD4 may directly regulate the expression of GATA6 in PDAC, pointing to a common predictive biomarker. To evaluate the relationship between SMAD4 mutations and GATA6 expression in human PDAC tumors, patients with paired SMAD4 mutation and GATA6 mRNA expression data in the TCGA and CPTAC were identified. In 321 patients (TCGA: n = 180; CPTAC: n = 141), the rate of SMAD4 alterations was 26.8%. The rate of SMAD4 alteration did not vary per tertile of normalized GATA6 expression (TCGA: p = 0.928; CPTAC: p = 0.828). In the TCGA, SMAD4 alterations and the basal-like phenotype were each associated with worse survival (log rank p = 0.077 and p = 0.080, respectively), but their combined presence did not identify a subset with uniquely inferior survival (p = 0.943). In the CPTAC, the basal-like phenotype was associated with significantly worse survival (p < 0.001), but the prognostic value was not influenced by the combined presence of SMAD4 alterations (p = 0.960). SMAD4 alterations were not associated with poor clinico-pathological features such as poor tumor grade, advanced tumor stage, positive lymphovascular invasion (LVI), or positive perineural invasion (PNI), compared with SMAD4-wildtype. Given that SMAD4 mutations were not associated with GATA6 expression or Moffitt subtype in two independent molecularly characterized PDAC cohorts, distinct biomarker-defined clinical trials are necessary.

The application of quantitative perfusion analysis of golden-angle radial sparse parallel MRI and R2∗ value for predicting pathological prognostic factors in rectal cancer

To investigate the diagnostic value of golden-angle radial sparse parallel magnetic resonance imaging (MRI) (GRASP) and R2∗ in predicting the prognostic factors of resectable rectal cancer. A total of 108 patients with rectal adenocarcinoma were included in this retrospective study. The volume transfer constant (Ktrans), rate constant (Kep), plasma volume fraction (Ve), and R2∗ were obtained. Univariate and multivariate logistic regression were conducted. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the imaging parameters. The Ktrans was found to be significantly higher in rectal cancers with positive lymph node metastasis (LNM), higher tumour grade, positive lymphovascular invasion (LVI), and higher ki-67 (all p<0.05). The Kep was also significantly higher in the LNM-positive group (p<0.001), while the R2∗ was higher in rectal cancers with LNM-positive, higher tumour grade, LVI-positive, and higher ki-67 (all p<0.05). Combining the Ktrans and R2∗ provided the highest area under the ROC curve (AUC) for LNM-positive and higher ki-67 tumours differentiation (0.790 and 0.823, respectively). Combining quantitative parameters of the Ktrans and R2∗ could be used to non-invasively predict pathological prognostic factors preoperatively.

Patients With Muscle-Invasive Bladder Cancer With Lymphovascular Invasion in Transurethral Resection Specimen Benefits Most From Platinum-Based Neoadjuvant Chemotherapy

PurposeThe survival benefit of neoadjuvant chemotherapy (NAC) before definitive radical cystectomy (RC) varied among patients, suggesting proper selection of patients for NAC to maximize the survival benefit. This study aimed to investigate the role of lymphovascular invasion (LVI) in transurethral resection (TUR) specimens in selecting patients with MIBC for NAC. MethodsTwo retrospective cohorts of patients with cT2-4aN0 MIBC who underwent RC from 2004 to 2015 provided by Lund University were included. Inverse probability weighting was applied to make the NAC-treated (NAC) and untreated (non-NAC) cohorts comparable. Survival benefits were estimated with Kaplan-Meier curves and Cox proportional hazards models. The primary endpoint was cancer-specific survival (CSS). LVI in TUR specimens and molecular taxonomies (BASE47, UNC, and LundTax) were examined, and bulk RNA-seq datasets were explored for LVI-relevant signatures. ResultsA total of 341 patients with cT2-4aN0 MIBC were included. The NAC cohort included 125 patients, whereas the non-NAC cohort included 216 patients. The 3-year CSS benefit of NAC was 7.1%. For patients with positive LVI in TUR specimens, the 3-year CSS benefit of NAC was 26.2% (48.1% vs. 74.3%), with a risk reduction of 56% (HR = 0.44, P = .03). A sensitivity analysis confirmed a significant interaction between LVI and NAC. This study failed to identify the molecular subtypes that maximized the survival benefit of NAC. Exploration of LVI-relevant signatures remains inconclusive. ConclusionsLVI in TUR specimens could help identify patients with MIBC who would derive maximal survival benefit from NAC. Further prospective validation is necessary.

Additional staining for lymphovascular invasion is associated with increased estimation of lymph node metastasis in patients with T1 colorectal cancer: Systematic review and meta-analysis.

Lymphovascular invasion (LVI) is a critical risk factor for lymph node metastasis (LNM), which requires additional surgery after endoscopic resection of T1 colorectal cancer (CRC). However, the impact of additional staining on estimating LNM is unclear. This systematic review aimed to evaluate the impact of additional staining on determining LNM in T1 CRC. We searched five electronic databases. Outcomes were diagnostic odds ratio (DOR), assessed using hierarchical summary receiver operating characteristic curves, and interobserver agreement among pathologists for positive LVI, assessed using Kappa coefficients (κ). We performed a subgroup analysis of studies that simultaneously included a multivariable analysis for other risk factors (deep submucosal invasion, poor differentiation, and tumor budding). Among the 64 studies (18,097 patients) identified, hematoxylin-eosin (HE) and additional staining for LVI had pooled sensitivities of 0.45 (95% confidence interval [CI] 0.32-0.58) and 0.68 (95% CI 0.44-0.86), specificities of 0.88 (95% CI 0.78-0.94) and 0.76 (95% CI 0.62-0.86), and DORs of 6.26 (95% CI 3.73-10.53) and 6.47 (95% CI 3.40-12.32) for determining LNM, respectively. In multivariable analysis, the DOR of additional staining for LNM (DOR 5.95; 95% CI 2.87-12.33) was higher than that of HE staining (DOR 1.89; 95% CI 1.13-3.16) (P = 0.01). Pooled κ values were 0.37 (95% CI 0.22-0.52) and 0.62 (95% CI 0.04-0.99) for HE and additional staining for LVI, respectively. Additional staining for LVI may increase the DOR for LNM and interobserver agreement for positive LVI among pathologists.

Comparison between a novel salivary marker and several clinical prognosticators in oral cavity cancer.

This study aimed to investigate the association between salivary matrix metalloproteinase-1 (MMP-1) and clinicopathological parameters of oral cavity squamous cell carcinoma (OSCC) and compare the prognostic efficacy of salivary MMP-1 and other established circulating markers for OSCC. Saliva specimens from 479 OSCC subjects were examined using an enzyme-linked immunosorbent assay. The area under the curve (AUC) values of salivary MMP-1 and other markers were calculated, and survival analyses were conducted using Kaplan-Meier and multivariate regression methods. Salivary MMP-1 showed good discrimination in predicting overall survival, with an AUC of 0.638, which was significantly higher than that of albumin (0.530, p = .021) and Charlson comorbidity index (0.568, p = .048) and comparable with neutrophil-to-lymphocyte ratio (0.620, p = .987), platelet-to-lymphocyte ratio (0.575, p = .125), and squamous cell carcinoma antigen (0.609, p = .605). Elevated levels of salivary MMP-1 were significantly associated with higher pT classification, pN classification, overall pathological stage, positive extranodal extension, tumor differentiation, positive lymphovascular invasion, positive perineural invasion, and tumor depth (p all <.05). Multivariate analyses indicated that a higher level of salivary MMP-1 (≥2060.0 pg/mL) was an independent predictive factor of poorer overall survival (adjusted hazard ratio: 1.421 [95% confidential interval: 1.014-1.989], p = .041). The study found that the salivary MMP-1 level was significantly associated with many adverse clinicopathological parameters of OSCC. In OSCC, it was found to have superior efficacy in predicting prognosis and was an independent prognostic factor of post-treatment outcome. 3.