Receptor for hyaluronan-mediated motility (RHAMM) defines an invasive niche associated with tumor progression and predicts poor outcomes in breast cancer patients.

Breast cancer invasion and metastasis result from a complex interplay between tumor cells and the tumor microenvironment (TME). Key oncogenic changes in the TME include aberrant synthesis, processing, and signaling of hyaluronan (HA). Hyaluronan-mediated motility receptor (RHAMM, CD168; HMMR) is an HA receptor enabling tumor cells to sense and respond to this aberrant TME during breast cancer progression. Previous studies have associated RHAMM expression with breast tumor progression; however, cause and effect mechanisms are incompletely established. Focused gene expression analysis of an internal breast cancer patient cohort confirmed that increased RHAMM expression correlates with aggressive clinicopathological features. To probe mechanisms, we developed a novel 27-gene RHAMM-related signature (RRS) by intersecting differentially expressed genes in lymph node (LN)-positive patient cases with the transcriptome of a RHAMM-dependent model of cell transformation, which we validated in an independent cohort. We demonstrate that the RRS predicts for poor survival and is enriched for cell cycle and TME-interaction pathways. Further analyses using CRISPR/Cas9-generated RHAMM-/- breast cancer cells provided direct evidence that RHAMM promotes invasion in vitro and in vivo. Immunohistochemistry studies highlighted heterogeneous RHAMM protein expression, and spatial transcriptomics associated the RRS with RHAMM-high microanatomic foci. We conclude that RHAMM upregulation leads to the formation of 'invasive niches', which are enriched in RRS-related pathways that drive invasion and could be targeted to limit invasive progression and improve patient outcomes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Prognostic value of a mandibular canal staging system for primary lesions in patients with lower gingival squamous cell carcinoma: a multicenter, retrospective study.

BACKGROUND: The Union for International Cancer Control and American Joint Committee on Cancer tumor staging system is used globally for treatment planning. As it may be insufficient for tumor staging of lower gingival carcinomas, we proposed the mandibular canal tumor staging system. In this study, we aimed to compare the two systems for such tumor staging and to identify prognostic markers. METHODS: This multicenter, retrospective study included patients with lower gingival squamous cell carcinoma who underwent radical surgery during 2001-2018. We compared survival rates (Kaplan-Meier estimator) and patient stratification according to the two systems. RESULTS: The proposed system yielded more balanced patient stratification than the existing system. Progression in the tumor grade according to the proposed system was associated with a poorer prognosis. The 5-year overall and disease-specific survival rates for the entire cohort were 74.9% and 81.8%, respectively. Independent factors affecting overall survival were tumor stage according to the proposed system, excision margins, and number of positive nodes, whereas those affecting disease-specific survival were excision margins and number of positive nodes. CONCLUSIONS: Subsite-specific tumor classification should be used for patients with oral cancer, and our results suggest that mandibular canal tumor classification may be effective for patients with lower gingival carcinoma.

BRAF V600E mutation mediates invasive and growth features in ameloblastoma.

OBJECTIVES: Ameloblastoma (AM), a locally aggressive tumor with extensive growth capacity, causes significant damage to the jaw and affects facial appearance. Although the high prevalence of BRAF V600E mutation in AM is known, its specific impacts on patients with AM remain unclear. Thus, the present study investigated the role of BRAF V600E mutation, thereby focusing on its impact on AM invasion and growth. MATERIALS AND METHODS: Immunohistochemical analysis was used to compare BRAF V600E, MMP2, MMP9, and Ki-67 expressions in AM (n = 49), normal oral mucosa (NOM) (n = 10), and odontogenic keratocyst (OKC) (n = 15) tissues. AM was further classified according to the presence or absence of BRAF V600E. The relationship between BRAF V600E and invasion as well as growth was evaluated. In addition, correlation analysis was performed using immunohistochemistry and confirmed via double-labeling immunofluorescence. Finally, comparative analyses using mass spectrometry, immunohistochemistry, and immunofluorescence were performed to explore and identify underlying mechanisms. RESULTS: AM exhibited a higher incidence of BRAF V600E mutation than NOM and OKC. BRAF V600E expression was positively correlated with the invasion-associated proteins MMP2 and MMP9 and the growth-related protein Ki-67. Proteomic data revealed that BRAF V600E primarily activates the MAPK signaling pathway in AM, particularly driving the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). CONCLUSIONS: In summary, the findings suggested that the BRAF V600E mutation enhances the invasion and growth abilities of AM via the MAPK/ERK signaling pathway. Thus, targeting BRAF V600E or the MAPK/ERK pathway may be a potential AM therapy.

Parameters to assess the necessity of adjuvant therapy for early-stage oral squamous cell carcinoma.

OBJECTIVE: One-third of head and neck squamous cell carcinomas are early-stage oral cavity squamous cell carcinomas (OCSCC). Despite a high curative rate, 20% of early-stage OCSCC patients do not achieve long-term survival. This study evaluates the role of adjuvant therapy (ADJ) in delaying disease progression and prolonging survival. METHODS: This single-institute retrospective cohort study enrolled 481 early-stage OCSCC patients, 16% (78/481) of whom received ADJ. It was reported according to the STROBE guidelines. Cox proportional hazards regression and Kaplan-Meier survival curves were employed to identify suitable candidates for ADJ. RESULTS: The 5-year locoregional recurrence-free survival (LR-RFS) and overall survival rates were 73.2% and 84.9%, respectively. Positive margins and advanced depth of invasion (DOI) were independent predictors of LR-RFS. For patients with positive margins, adjuvant chemoradiotherapy (CRT) was superior to adjuvant radiotherapy alone in improving LR-RFS (hazard ratios for adjuvant CRT vs. none, 0.042; adjuvant radiotherapy alone vs. none, 0.702). Excluding positive margins, advanced DOI was the most critical factor in assessing the need for ADJ. Positive margins and advanced DOI were more appropriate criteria than EORTC 22931/RTOG 9501 for evaluating adjuvant CRT. CONCLUSIONS: Adjuvant CRT was indicated for patients with positive margins and advanced DOI to improve survival outcomes.

Tumor thickness is associated with metastasis in patients with submucosal invasive adenocarcinoma of the esophagogastric junction.

In submucosal invasive adenocarcinoma of the esophagogastric junction (pT1b-SM AEG), the extent of tumor submucosal (SM) invasion is measured using the vertical depth of SM invasion with the muscularis mucosa. This study aimed to investigate whether tumor thickness and depth of invasion without accounting for muscularis mucosa were superior to the vertical depth of SM invasion as metastasis predictors. We enrolled patients with pT1b-SM AEG who underwent endoscopic resection or surgical resection (SR) at our institution between January 2011 and September 2019 and were followed up for ≥2 years. The relationship between metastasis and clinicopathological factors was examined. Metastasis was defined as pathologically confirmed lymph node metastasis in the surgical specimen or recurrence during follow-up. This study included 57 patients (44 men; median age, 72 years). Endoscopic resection and SR were performed in 16 and 41 patients, respectively. Nine patients were diagnosed with metastasis: five who underwent SR showed pathologically confirmed lymph node metastasis in the surgical specimens, and four experienced recurrences during a median follow-up of 48 months. Univariate analyses showed that tumor thickness was significantly associated with metastasis (P = 0.021), and the vertical depth of SM invasion (P = 0.48) and depth of invasion (P = 0.38) were not. Furthermore, in multivariate analysis, tumor thickness ≥2800 µm (odds ratio, 38.70; P = 0.013) was a significant predictor for metastasis. Tumor thickness may be a more convenient and useful predictor of metastasis in patients with pT1b-SM AEG than the vertical depth of SM invasion.

[Prognostic factors of patients with muscle invasive bladder cancer with intermediate-to-high risk prostate cancer].

OBJECTIVE: To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer (MIBC) with intermediate-to-high-risk primary prostate cancer. METHODS: From January 2012 to October 2023, the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed. All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study. Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients. For significant influencing factors (pathological T stage, M stage and perineural invasion of bladder cancer), survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors. RESULTS: A total of 32 patients were included in this study. The mean age was (72.5±6.6) years; the median preoperative total prostate specific antigen (tPSA) was 6.68 (2.47, 6.84) µg/L; the mean preoperative creatinine was (95±36) µmol/L, and the median survival time was 65 months. The majority of the patients (87.5%) had high-grade bladder cancer, 53.1% had lymphatic invasion, and 31.3% had perineural invasion. Prostate involvement was observed in 25.0% of the cases, and the positive rate of soft-tissue surgical margin was 37.5%. Multivariate Cox analysis revealed that preoperative creatinine level (HR=1.02, 95%CI: 1.01-1.04), pathological stage of bladder cancer T3 (HR=11.58, 95%CI: 1.38-97.36) and T4 (HR=19.53, 95%CI: 4.26-89.52) metastasis of bladder cancer (HR=9.44, 95%CI: 1.26-70.49) and perineural invasion of bladder cancer (HR=6.26, 95%CI: 1.39-28.27) were independent prognostic factors (P < 0.05). Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3, T4, M1, and perineural invasion were unfavorable factors affecting the patients' survival prognosis (P < 0.05). CONCLUSION: Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis. High preoperative serum creatinine, T3 or T4 pathological stage of bladder cancer, metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

Repeat Transurethral Resection of Muscle-invasive Bladder Cancer Prior to Radical Cystectomy is Prognostic but Not Therapeutic.

PURPOSE: We sought to evaluate the impact of repeat transurethral resection of bladder tumor prior to radical cystectomy on oncologic outcomes in a contemporary cohort at a tertiary care center. MATERIALS AND METHODS: An Institutional Review Board approved review of 657 patients diagnosed with muscle-invasive bladder cancer who underwent radical cystectomy at our institution for clinical stage T2 urothelial carcinoma between 2005 and 2017 was performed. Patients with and without repeat transurethral resection of bladder tumor were matched 1-to-1 by propensity score. Matching was done by age, gender, receipt of neoadjuvant chemotherapy, preoperative hydronephrosis, variant histology, lymphovascular invasion, or carcinoma in situ on index transurethral resection of bladder tumor. RESULTS: A total of 548 patients with muscle-invasive bladder cancer were included after matching (2 groups of 274 patients). Kaplan-Meier estimates of recurrence-free and overall survival demonstrated no significant difference based upon performance of repeat transurethral resection of bladder tumor (P = 1.0 and P = .3, respectively). When outcomes were stratified by pathology of repeat transurethral resection of bladder tumor specimens, those with pT0 had superior recurrence-free and overall survival compared to those with residual muscle invasive disease (P < .001 and P = .001, respectively). Notably, more than 60% of patients who were pT0 on repeat transurethral resection of bladder tumor had residual disease at the time of radical cystectomy. CONCLUSIONS: Repeat transurethral resection of bladder tumor prior to radical cystectomy, irrespective of receipt of neoadjuvant chemotherapy, was not associated with improved survival outcomes in this propensity score matched muscle-invasive bladder cancer cohort. The absence of residual tumor on pathological evaluation of repeat transurethral resection of bladder tumor specimen was prognostic and was associated with improved survival outcomes. However, a large percentage of patients with pT0 disease on repeat transurethral resection of bladder tumor had residual disease on radical cystectomy pathology.

CT-based quantification of trachea shape to detect invasion by thyroid cancer.

OBJECTIVE: This study aims to develop a CT-based method for quantifying tracheal shape and evaluating its ability to distinguish between cases with or without tracheal invasion in patients with thyroid carcinoma. METHODS: A total of 116 quantitative shape features, including 56 geometric moments and 60 bounding shape features, were defined. The tracheal lumen was semi-automatically defined with a CT threshold of less than - 500 HU. Three contiguous slices with the 1st, 2nd, and 3rd smallest trachea lumen areas were contiguously selected, and the appropriate number of slices to be included was determined. Fifty-six patients with differentiated thyroid carcinoma (DTC) invading the trachea and 22 patients with DTC but without invasion were retrospectively included. A receiver operating characteristic (ROC) curve was applied to select the representative shape features and determine the optimal threshold. RESULTS: 23.3%, 25.9%, and 24.1% of the features displayed an area under the ROC curve (AUC) ≥ 0.800 when derived from 1, 2, and 3 slices, respectively. Calculating feature values from two slices with the 1st and 2nd smallest tracheal lumen area were considered appropriate. Six final features, including 3 geometric moments and 3 bounding shape features, were selected to determine the tracheal invasion status of DTC and displayed AUCs of 0.875-0.918, accuracies of 0.821-0.891, sensitivities of 0.813-0.893, and specificities of 0.818-0.932, outperforming the visual evaluation results. CONCLUSIONS: Geometric moments and bounding shape features can quantify the tracheal shape and are reliable for identifying DTC tracheal invasion. The selected features quantified the extent of tracheal deformity in DTC patients with and without tracheal invasion. CLINICAL RELEVANCE STATEMENT: Six geometric features provide a non-invasive, semi-automated evaluation of the tracheal invasion status of thyroid cancer. KEY POINTS: • A novel method for quantifying tracheal shape using 56 geometric moments and 60 bounding shape features was developed. • Six features identify tracheal invasion by thyroid carcinoma. • The selected features quantified the extent of tracheal deformity in differentiated thyroid carcinoma patients with and without tracheal invasion.

Radiomics nomogram for the prediction of microvascular invasion of HCC and patients' benefit from postoperative adjuvant TACE: a multi-center study.

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.

Aorta and tracheobronchial invasion in esophageal cancer: comparing diagnostic performance of 3.0-T MRI and CT.

OBJECTIVES: To compare between the diagnostic performance of 3.0-T MRI and CT for aorta and tracheobronchial invasion in patients with esophageal cancer (EC). METHODS: We prospectively included patients with pathologically confirmed EC from November 2018 to June 2021, who had baseline stage of T3-4N0-2M0 and restaging after neoadjuvant chemotherapy. All patients underwent contrast-enhanced CT and MRI of the thorax. Two independent blinded radiologists scored image quality and the presence of invasion. Agreements between the two readers were calculated using kappa test. The sensitivity, specificity, accuracy, positive predict value (PPV), and negative predict value (NPV) of MRI and CT in evaluating invasion were calculated. The net reclassification index (NRI) was used to evaluate the change in the number of patients correctly classified by MRI and CT. RESULTS: A total of 70 patients (64.8 ± 9.0 years; 53 men) were enrolled. Inter-reader agreements of image quality scores and presence of invasion by MRI and CT between the two readers were almost perfect (kappa > 0.80). The accuracy of MRI in evaluating thoracic aorta invasion was significantly higher than that of CT (reader 1: 90.0% vs. 71.4%; reader 2: 92.9% vs. 70.0%, respectively), and the accuracy of MRI in evaluating tracheobronchial invasion also was significantly higher than that of CT (reader 1: 92.9% vs. 72.9%; reader 2: 95.7% vs. 70.0%, respectively). NRI values were positive in both the evaluation of aorta and tracheobronchial invasion. CONCLUSIONS: The accuracy of 3-T MRI in determining thoracic aorta and tracheobronchial invasion is significantly higher than that of CT. KEY POINTS: • 3.0-T MRI was significantly more accurate than CT in assessing invasion of the thoracic aorta in patients with esophageal cancer. • 3.0-T MRI was also significantly more accurate than CT in assessing tracheobronchial invasion in patients with esophageal cancer. • 3.0-T MRI has a higher diagnostic performance than CT in evaluating patients with suspected aortic or tracheobronchial invasion in esophageal cancer.

The role of DDX46 in breast cancer proliferation and invasiveness: A potential therapeutic target.

DDX46, a member of DEAD-box (DDX) proteins, is associated with various cancers, while its involvement in the pathogenesis of breast cancer hasn't been reported so far. The study demonstrated the overexpression of DDX46 in human breast cancer cells and tissue samples, and correlated with high histological grade and lymph node metastasis. Downregulation of DDX46 in the breast cancer cell lines inhibited their proliferation and invasiveness in vitro. Furthermore, the growth of MDA-MB-231 xenografts was suppressed in nude mice by DDX46 knockingdown. Taken together, our findings suggest that DDX46 is an oncogenic factor in human breast cancer, and a potential therapeutic target.

[Clinical factors affecting the prognosis of lower gingival squamous cell carcinoma].

OBJECTIVE: To define the clinical factors that influence local recurrence and survival in patients with lower gingival squamous cell carcinoma (LGSCC) and determine whether bone invasion is an independent prognostic factor for them. METHODS: A total of 104 patients with LGSCC hospitalized in Peking University Stomatology Hospital from June 2013 to December 2015 were enrolled in this retrospective study.All the patients were followed-up for more than 3 years.The degree of bone invasion was assessed using preoperative imaging data (CT and panoramic radiograph).The degree of bone invasion was divi-ded into four categories: no bone invasion, invasion of cortical bone, invasion of bone marrow cavity, and invasion of the mandibular canal.According to the central position of tumor, it was divided into two types: anterior mandibular invasion (anterior region of the mental foramen) and posterior mandibular invasion (posterior region of the mental foramen). RESULTS: of different invasion depth groups were compared using Mann-Whitney U test.P value < 0.05 was considered to be statistically significant.Kaplan-Meier survival analysis method was used to draw survival curve, and COX regression was used to explore the risk ratio (HR) and 95% confidence interval (CI) of prognostic factors of LGSCC. RESULTS: The follow-up results showed that the 1-, 3-, and 5-year survival rates of LGSCC in this group were 91%, 84%, 82%, respectively.32.7%(34/104) of patients had cervical lymph node metastasis.The cervical lymph node metastasis rate of the anterior segment of the mandible was 12.5%(2/16), and 36.4%(32/88) for the posterior segment of the mandible (P < 0.05).Univariate and multivariate COX analysis showed that the N stage and local recurrence were the prognostic factors of LGSCC patients (P < 0.05). CONCLUSION: As the degree of mandibular invasion increases, the prognosis of patients with mandibular gum cancer becomes worse.N stage and local recurrence are prognostic risk factors for LGSCC.The incidence of cervical lymph node metastasis for LGSCC is related to the primary tumor location.It is concluded that tumors located at the posterior of the mandible might be more prone to cervical lymph node metastasis than the anterior of the mandible.Thus various levels of cervical lymph node dissection strategies should be adopted for different sites of LGSCC.

Fertility-sparing treatment for serous borderline ovarian tumors with extra-ovarian invasive implants: Analysis from the MITO14 study database.

OBJECTIVE: Only 10-15% of serous borderline ovarian tumors (BOTs) with extra-ovarian disease have invasive implants, and conservative treatments have been rarely reported. The MITO14 is a multi-institutional retrospective study conducted with the aim of systematically collecting data from consecutive BOT patients. The present analysis reports the oncological and reproductive outcomes of women with serous BOT and invasive implants registered into the MITO14 database and conservatively treated between August 2002 and May 2019. METHODS: Thirteen patients (FIGO2014 stage II-III serous BOT with invasive implants) were recruited. Primary and secondary endpoints were, respectively, recurrence and death rates, and pregnancy and live birth rates. Only patients undergoing fertility-sparing surgery (FSS) were included, while patients were excluded in case of: age > 45 years; second tumor(s) requiring therapy interfering with the treatment of BOT. RESULTS: Median follow-up time from primary cytoreduction was 146 months (range 27-213 months). Eleven patients (84.6%) experienced at least one recurrence (median time to first relapse 17 months, range 4-190 months), all of these undergoing secondary surgery (FSS in 7). Five patients attempted to conceive: 3 achieved at least one pregnancy and 2 gave birth at least to a healthy child. At the end of the observation period, all patients were alive with no evidence of disease. CONCLUSIONS: Fertility-sparing treatment should be considered in a context of serous BOT with invasive implants. Despite the high rate of recurrence, FSS provides good chances of reproductive success without a negative impact on overall survival.

Using CT to evaluate mediastinal great vein invasion by thymic epithelial tumors: measurement of the interface between the tumor and neighboring structures.

OBJECTIVES: For thymic epithelial tumors, simple contact with adjacent structures does not necessarily mean invasion. The purpose of our study was to develop a simple noninvasive technique for evaluating organ invasion using routine pretreatment computed tomography (CT). METHODS: This retrospective study analyzed the pathological reports on 95 mediastinal resections performed between January 2003 and June 2020. Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) and maximum tumor diameter (Dmax) was measured, after which Adist/Dmax (A/D) ratios were calculated. Receiver operating characteristic (ROC) curves were used to analyze the Adist and A/D ratios. RESULTS: An Adist cut-off of 37.5 mm best distinguished between invaded and non-invaded mediastinal great veins based on ROC curves. When Adist > 37.5 mm was used for diagnosis of invasion of the brachiocephalic vein (BCV) or superior vena cava (SVC), the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the ROC curve for diagnosis of invasion were 61.9%, 92.5%, 81.25%, 82.2%, 81.97%, and 0.76429, respectively. Moreover, there were significant differences between BCV/SVC Adist > 37.5 mm and ≤ 37.5 mm for 10-year relapse-free survival and 10-year overall survival (p < 0.01). CONCLUSIONS: When diagnosing invasion of the mediastinal great veins based on Adist > 37.5 mm, we achieved a higher performance level than the conventional criteria such as irregular interface with an absence of the fat layer. Measurement of Adist is a simple noninvasive technique for evaluating invasion using CT. Key Points • Simple contact between the primary tumor and adjacent structures on CT does not indicate direct invasion. • Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) is a simple noninvasive technique for evaluating invasion. • Adist > 37.5 mm can be a supportive tool to identify invaded mediastinal great veins and surgical indications for T3 and T4 invasion by thymic epithelial tumors.

Diagnostic and prognostic value of magnetic resonance imaging in the detection of tumor depth of invasion and bone invasion in patients with oral cavity cancer.

PURPOSE: To evaluate the accuracy of preoperative contrast-enhanced magnetic resonance imaging (MRI) in the assessment of radiological depth of invasion (rDOI) and bone invasion in patients with oral cavity cancer, and the prognostic value of preoperative rDOI. MATERIALS AND METHODS: This retrospective study included patients with surgically resected oral cavity cancer and preoperative MRI acquired within four weeks before surgery. Two readers evaluated the MRI to assess the superficial and deep bone invasion, preoperative T stage, and measured the rDOI. The rDOI was compared to the histopathological DOI (pDOI), used as reference standard. Prognostic value of preoperative features for the disease-specific survival was evaluated using the Kaplan-Meier curve and multivariable Cox proportional hazards analysis. RESULTS: The final population included 80 patients (50 males, mean age 67.7 ± 13.6 years). There was a strong statistically significant correlation between the rDOI (median 10 mm) and the pDOI (median 9 mm) (ρ: 0.978, p < 0.001). The agreement between MRI and histopathological T stage was excellent (k = 0.93, 95% CI 0.86, 0.99). The sensitivity and specificity of preoperative MRI were 93.3% and 98.8% for deep bone invasion, while they were 75.0% and 95.8% for superficial bone invasion, respectively. The rDOI > 10 mm was associated with poorer disease-specific survival (log-rank p = 0.016). The rDOI remained the only independent preoperative predictor associated with poorer disease-specific survival at multivariable analysis (hazard ratio 5.5; 95% CI 1.14, 26.58; p = 0.033). CONCLUSION: Preoperative MRI is accurate for the assessment of DOI and bone invasion. The rDOI is an independent preoperative predictor of disease-specific survival in patients with oral cavity cancer.

Contrast-enhanced ultrasound: a valuable modality for extracapsular extension assessment in papillary thyroid cancer.

OBJECTIVES: To evaluate the diagnostic accuracy of preoperative contrast-enhanced ultrasound (CEUS) to detect extracapsular extension (ECE) and identify the relationship between ECE and nodule enhancement patterns in patients with papillary thyroid cancer (PTC). METHODS: Patients with suspected thyroid cancer underwent ultrasound (US) and CEUS examinations. The US and CEUS features of the PTC nodules and thyroid capsule were recorded and classified individually. The accuracy of US and CEUS in detecting ECE was compared individually, and its relationship with various tumour enhancement patterns was analysed. The presence or absence of ECE and cervical lymph node metastasis (LNM) was confirmed pathologically. RESULTS: The final dataset included 119 patients with 124 PTC nodules. Seventy-two (60.5%) of these patients with PTC had no ECE (including 38 patients with single capsule invasion), while the remaining 52 had ECE. A significant difference was found in nodules with non-capsule invasion, single capsule invasion, and ECE between the cervical LNM and non-LNM groups (p < 0.01). Receiver operating characteristic curve analysis demonstrated that area under the curve (AUC) of ECE for cervical LNM was higher than that of capsule invasion (71.9% vs. 49.6%). Moreover, the CEUS images acquired to detect ECE showed higher AUC values than those of US images (79.4% vs. 65.8%) (p = 0.02). Among the PTC nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%). CONCLUSIONS: Compared with conventional US, CEUS is a more valuable and non-invasive imaging modality to detect ECE. KEY POINTS: • Single capsular invasion was a poor predictor of cervical lymph node metastasis, while extracapsular extension assessments were clinically significant for predicting cervical lymph node metastasis. • CEUS is better than conventional US in detecting extracapsular extension in papillary thyroid carcinoma (AUC: 79.4% vs. 65.8%) (p = 0.02). • Among the thyroid papillary carcinoma nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of single capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%).

Determining the invasiveness of ground-glass nodules using a 3D multi-task network.

OBJECTIVES: The aim of this study was to determine the invasiveness of ground-glass nodules (GGNs) using a 3D multi-task deep learning network. METHODS: We propose a novel architecture based on 3D multi-task learning to determine the invasiveness of GGNs. In total, 770 patients with 909 GGNs who underwent lung CT scans were enrolled. The patients were divided into the training (n = 626) and test sets (n = 144). In the test set, invasiveness was classified using deep learning into three categories: atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive pulmonary adenocarcinoma (IA). Furthermore, binary classifications (AAH/AIS/MIA vs. IA) were made by two thoracic radiologists and compared with the deep learning results. RESULTS: In the three-category classification task, the sensitivity, specificity, and accuracy were 65.41%, 82.21%, and 64.9%, respectively. In the binary classification task, the sensitivity, specificity, accuracy, and area under the ROC curve (AUC) values were 69.57%, 95.24%, 87.42%, and 0.89, respectively. In the visual assessment of GGN invasiveness of binary classification by the two thoracic radiologists, the sensitivity, specificity, and accuracy of the senior and junior radiologists were 58.93%, 90.51%, and 81.35% and 76.79%, 55.47%, and 61.66%, respectively. CONCLUSIONS: The proposed multi-task deep learning model achieved good classification results in determining the invasiveness of GGNs. This model may help to select patients with invasive lesions who need surgery and the proper surgical methods. KEY POINTS: • The proposed multi-task model has achieved good classification results for the invasiveness of GGNs. • The proposed network includes a classification and segmentation branch to learn global and regional features, respectively. • The multi-task model could assist doctors in selecting patients with invasive lesions who need surgery and choosing appropriate surgical methods.

Concurrent lymphovascular and perineural invasion after preoperative therapy for gastric adenocarcinoma is associated with decreased survival.

BACKGROUND AND OBJECTIVES: We sought to evaluate the impact of lymphovascular invasion (LVI) and perineural invasion (PNI) on survival outcomes in gastric cancer patients treated with preoperative therapy. METHODS: Patients with gastric cancer treated with preoperative therapy and potentially curative resection were stratified according to the presence of LVI, PNI, or both. Kaplan-Meier and Cox regression analyses were used to evaluate the impact on overall survival (OS) and disease-free survival (DFS). RESULTS: The study included 281 patients, of whom 93 (33%) had LVI, 69 (25%) had PNI, 51 (18%) had both LVI and PNI, and 170 (61%) had neither. LVI and PNI were each associated with higher ypT and ypN categories and more positive lymph nodes (all p < .001), associations that were emphasized with both factors present. On multivariable analyses, ypN (p < .001) and concurrent LVI/PNI (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.55-4.45; p = .001) were predictive of OS and DFS (ypN: p < .001; both LVI/PNI: HR: 2.27; 95% CI: 1.34-3.82; p = .002). CONCLUSIONS: Gastric cancer patients with concurrent LVI and PNI after preoperative therapy have more advanced disease and worse survival outcomes than patients with neither or only one of these factors.

Small Neuroendocrine Tumors of the Whole Gastrointestinal Tract Performed Endoscopic or Surgical Resections Also Show Positive for Lymphovascular Invasion.

BACKGROUND AND AIMS: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. METHODS: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. RESULTS: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases <5 mm, with a lymphovascular invasion rate of 8.7% for those 5-10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. CONCLUSIONS: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

[Risk factors of renal sinus invasion in clinical T1 renal cell carcinoma patients undergoing nephrectomy].

OBJECTIVE: To summarize the clinicoradiological characteristics of clinical T1 renal cell carcinoma patients and to investigate the risk factors of renal sinus invasion in cT1 renal cell carcinoma patients undergoing nephrectomy. METHODS: A retrospective study was conducted in cT1 renal cell carcinoma patients from January 2016 to August 2019 in Department of Urology, Peking University Third Hospital, who underwent partial or radical nephrectomy by analyzing clinicopathological and radiological data. The influencing factors of renal sinus invasion for cT1 renal cell carcinoma were determined by χ2 test, Mann-Whitney U test and Logistic regression analysis. RESULTS: A total of 507 patients were enrolled, including 354 males (69.8%) and 153 females (30.2%). The median age was 59 years and the median body mass index (BMI) was 25.5 kg/m2. Eighteen patients (3.6%) had gross hematuria preoperatively. The median tumor diameter was 3.5 cm. Three hundred twenty-two patients (63.5%) were staged clinical T1a and 165 cases (36.5%) were staged clinical T1b. The median R.E.N.A.L. score was 8. Three hundred fifty-nine patients (70.8%) had regular tumor border and 148 (29.2%) irregular. All the patients underwent surgical treatment, including 186 (36.7%) partial nephrectomy and 321 (63.3%) radical nephrectomy. Postoperative pathology showed seventy-five patients (14.8%) had renal sinus invasion, including 18 in cT1a (5.6%) and 57 in cT1b (30.8%). Univariate analysis showed that age (P=0.020), R.E.N.A.L. score (R value, E value, N value, P < 0.001) and tumor border (P < 0.001) were associated risk factors for cT1 renal cell carcinoma with renal sinus invasion. On multivariate binary Logistic analysis, R.E.N.A.L. score (P≤0.020) and irregular tumor border (P=0.001) were independent risk factors. CONCLUSION: For cT1 renal cell carcinoma patients undergoing nephrectomy, about 15% had renal sinus invasion postoperatively. High R.E.N.A.L. score and irre-gular tumor border help predicting cT1 renal cell carcinoma renal sinus invasion.