Development Of Node Metastases Research Articles

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

MAOB expression correlates with a favourable prognosis in prostate cancer, and its genetic variants are associated with the metastasis of the disease.

Monoamine oxidase B (MAOB), a neurotransmitter-degrading enzyme, was reported to reveal conflicting roles in various cancers. However, the functional role of MAOB and impacts of its genetic variants on prostate cancer (PCa) is unknown. Herein, we genotyped four loci of MAOB single-nucleotide polymorphisms (SNPs), including rs1799836 (A/G), rs3027452 (G/A), rs6651806 (A/C) and rs6324 (G/A) in 702 PCa Taiwanese patients. We discovered that PCa patients carrying the MAOB rs6324 A-allele exhibited an increased risk of having a high initial prostate-specific antigen (iPSA) level (>10 ng/mL). Additionally, patients with the rs3027452 A-allele had a higher risk of developing distal metastasis, particularly in the subpopulation with high iPSA levels. In a subpopulation without postoperative biochemical recurrence, patients carrying the rs1799836 G-allele had a higher risk of developing lymph node metastasis and recurrence compared to those carrying the A-allele. Furthermore, genotype screening in PCa cell lines revealed that cells carrying the rs1799836 G-allele expressed lower MAOB levels than those carrying the A-allele. Functionally, overexpression and knockdown of MAOB in PCa cells respectively suppressed and enhanced cell motility and proliferation. In clinical observations, correlations of lower MAOB expression levels with higher Gleason scores, advanced clinical T stages, tumour metastasis, and poorer prognosis in PCa patients were noted. Our findings suggest that MAOB may act as a suppressor of PCa progression, and the rs3027452 and rs1799836 genetic variants of MAOB are linked to PCa metastasis within the Taiwanese population.

Restrospective reappraisal of the prognostic classification of spitzoid melanocytic neoplasms after BRAF and NRAS mutation characterisation: a single institution experience.

The current WHO classification of melanocytic tumours excludes neoplasms showing BRAF or NRAS mutations from the Spitz category. This study aimed to review and reclassify atypical melanocytic tumours with spitzoid morphological features diagnosed between 2009 and 2021 in our hospital after expanding the molecular profile, including BRAF and NRAS mutations in all cases. A total of 71 neoplasms showing spitzoid features (Spitz-like) and atypia were included. The risk of progression of tumours was first studied by integrating the morphology, immunohistochemistry (p16, Ki67, HMB45 and PRAME) and fluorescence in-situ hybridisation (FISH) results (melanoma multiprobe and 9p21). In a second step, after expanding the molecular study, including BRAF and NRAS mutational status, the neoplasms were finally classified into four subgroups: atypical Spitz tumour (AST, n = 45); BRAF-mutated naevus/low-grade melanocytoma with spitzoid morphology (BAMS, n = 2); Spitz melanoma (SM, n = 14); and BRAF or NRAS mutated melanoma with spitzoid features (MSF, n = 10). Follow-up of patients revealed uneventful results for AST and BAMS. Only one SM presented lymph node metastasis after 134 months. Conversely, patients with MSF showed an unfavourable outcome: three developed lymph node metastases after a mean time of 22 months, with one patient presenting distant metastasis and dying of the disease 64 months from diagnosis. The progression-free survival showed significant differences between the four groups of spitzoid tumours (P < 0.001) and between both melanoma subtypes (P = 0.012). The classification and prognostication of atypical neoplasms with spitzoid features requires the integration of histomorphology with the molecular investigation of tumours, which should include BRAF and NRAS mutational status.

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha-smooth muscle actin-positive fibrosis and COMP-expressing stromal cells.

Neuroendocrine tumors of the small intestine (SI-NETs) often develop lymph node metastasis (LNM)-induced mesenteric fibrosis (MF). MF can cause intestinal obstruction as well as ischemia and render surgical resection technically challenging. The underlying pathomechanisms of MF are still not well understood. We examined mesenteric LNM and the surrounding stroma compartment from 24 SI-NET patients, including 11 with in situ presentation of strong MF (MF+) and 13 without MF (MF-). Differential gene expression was assessed with the HTG EdgeSeq Oncology Biomarker Panel comparing MF+ with MF- within LNM and paired stromal samples, respectively. Most interesting differentially expressed genes were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in combination with validation of associated protein levels utilizing immunohistochemistry (IHC) staining of MF+ and MF- formalin-fixed, paraffin-embedded (FFPE) patient samples. Overall, 14 genes measured with a 2549-gene expression panel were differentially expressed in MF+ patients compared to MF-. Of those, nine were differentially expressed genes in LNM and five genes in the stromal tissue (>2-fold change, p < .05). The top hits included increased COMP and COL11A1 expression in the stroma of MF+ patients compared to MF-, as well as decreased HMGA2, COL6A6, and SLC22A3 expression in LNM of MF+ patients compared to LNM of MF- patients. RT-qPCR confirmed high levels of COMP and COL11A1 in stroma samples of MF+ compared to MF- patients. IHC staining confirmed the enrichment of α-smooth muscle actin-positive fibrosis in MF+ compared to MF- patients with corresponding increase of COMP-expressing stromal cells in MF+. Since COMP is associated with the known driver for fibrosis development transforming growth factor beta and with a cancer-associated fibroblasts enriched environment, it seems to be a promising new target for MF research.

Impact of LINC00312 gene polymorphism coupled with habitual risks on buccal mucosa cancer.

Oral squamous cell carcinoma (OSCC) is a prevalent and lethal malignancy with a diverse etiology. LINC00312 is a long intergenic non-coding RNA that functions as a signal hub to regulate the progression and treatment of head and neck cancer. The aim of this study was to evaluate the effect of LINC00312 single nucleotide polymorphisms (SNPs) on the development of oral cancer. Two LINC00312 SNPs, namely rs12497104 and rs164966, were investigated among 469 male patients with cancer of buccal mucosa and 1194 gender- and age-matched controls. No significant correlation was observed between these two SNPs and the occurrence of OSCC in the case and control groups. While assessing the clinicopathological features, carriers of at least one minor allele of rs164966 (GA and GG) were less prone to develop lymph node metastasis (adjusted odds ratio [AOR], 0.666; 95% confidence interval [CI], 0.447-0.991; p=0.045) in comparison with homozygous carriers of the major allele (AA). Subsequent stratifying surveys revealed that this genetic association with nodal spread was seen only in cases who habitually chewed betel quid (AOR, 0.616; 95% CI, 0.386-0.985; p=0.042) or smoked cigarettes (AOR, 0.612; 95% CI, 0.393-0.953; p=0.029), but undetected in cases free of these main behavioral risks. Our results indicate an interactivity of LINC00312 rs164966 with lifestyle-related risks on modulating OSCC progression.

Application of machine learning algorithms to predict lymph node metastasis in gastric neuroendocrine neoplasms

BackgroundNeuroendocrine neoplasms (NENs) are tumors that originate from secretory cells of the diffuse endocrine system and typically produce bioactive amines or peptide hormones. This paper describes the development and validation of a predictive model of the risk of lymph node metastasis among gastric NEN patients based on machine learning platform. MethodsIn this investigation, data from 1256 patients were used, of whom 119 patients from the First Affiliated Hospital of Soochow University in China and 1137 cases from the surveillance epidemiology and end results (SEER) database were combined. Six machine learning algorithms, including the logistic regression model (LR), random forest (RF), decision tree (DT), Naive Bayes (NB), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), were used to build the predictive model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. ResultsAmong the 1256 patients with gastric NENs, 276 patients (21.97 %) developed lymph node metastasis. T stage, tumor size, degree of differentiation, and sex were predictive factors of lymph node metastasis. The RF model achieved the best predictive performance among the six machine learning models, with an AUC, accuracy, sensitivity, and specificity of 0.81, 0.78, 0.76, and 0.82, respectively. ConclusionThe RF model provided the best prediction and can help physicians determine the lymph node metastasis risk of gastric NEN patients to formulate individualized medical strategies.

Development of a Screening Nomogram for Regional Lymph Node Metastasis Development in Muscle Invasive Bladder Cancer after Multiagent Systemic Therapy

A reliable method of identifying clinically node negative bladder cancer patients at greater risk of developing lymph node metastasis and may require intensified therapy is needed. The purpose of this study was to create a nomogram to quantify the risk for regional lymphatic involvement in non-metastatic muscle invasive bladder cancer. Usingthe National Cancer Database, patients with clinical T2-4N0M0 urothelial carcinoma of the bladder between the years of 2004 - 2020 were selected. All patients completed multiagent chemotherapy followed by surgery for pathologic nodal staging to determine presence or absence of nodal disease. No neoadjuvant radiation therapy was allowed and patients with history of prior malignancies were excluded. Following a 70:30 training to testing data split, baseline variables were assessed using univariate logistic regression. Variables were selected for inclusion in the multivariate logistic regression model using a combination of previously reported findings in the literature and/or if found to have a p-value < 0.05 on univariate analysis. A nomogram was constructed using this final model with assessment using calibration plots and the area under the receiver operating characteristics curve (AUC), respectively. An empiric cut point was chosen at 95% sensitivity to identify patients at "high" and "low" risk for pathologic nodal disease with overall assessment in both cohorts using chi-square. A total of 6194patients were identified for study with a median age of 65 years (IQR = 58 - 71 years). Most patients were male (68.0%) with T2 disease (81.2%). The final multivariate model included age at time of diagnosis (OR = 0.99; 95% CI = 0.99 - 1.00; p = 0.172), time from diagnosis to initiation of chemotherapy (OR = 1.00; 95% CI = 1.00 - 1.01; p = 0.005), papillary histology (OR = 0.85; 95% CI = 0.72 - 1.01; p = 0.068), and clinical T stage (Table 1). Model calibration demonstrated excellent goodness-of-fit with good discrimination (AUC = 0.644). Within the training data, high risk patients were seen to have a twofold increase in pathologic nodal disease (N = 835/3924, 21.2%) when compared to those identified as low risk (N = 38/347, 9.9%) (p < 0.001). Validation within the testing data set demonstrated similar results with pathologic node rates of 22.8% and 7.8% for high- and low-risk patients, respectively (AUC = 0.645, p < 0.001). This study demonstrates a clinically applicable risk stratification tool for identifying patients at risk for developing lymphadenopathy in T2-4 bladder cancer and may help guide future research in selecting patients eligible for escalation of therapy. Future studies should aim to externally validate this tool within prospective cohorts, and seek to determine if this nomogram may provide further prognostic utility.

Association of CDKN2A/B mutations, PD-1, and PD-L1 with the risk of acute lymphoblastic leukemia in children

PurposeCurrently, the significance of CDKN2A/B mutations in the pathogenesis and prognosis of acute lymphoblastic leukemia (ALL) is inconclusive. In this study, we analyzed the genetic and clinical features of children with CDKN2A/B mutations in ALL. In addition, we evaluated the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in serum and explored their role in the susceptibility of childhood ALL.MethodsWe sequenced CDKN2A/B in the peripheral blood of 120 children with ALL and 100 healthy children with physical examination. The levels of CD4+ T, CD8+ T, and NK cells were measured by flow cytometry (FCM). Furthermore, the expression of PD-1 and PD-L1 was detected by ELISA.ResultsWe found 32 cases of CDKN2A rs3088440 and 11 of CDKN2B rs2069426 in 120 ALL children. Children with ALL in the CDKN2A rs3088440 were more likely to have hepatosplenomegaly (P = 0.019) and high risk (P = 0.014) than the wild group. In contrast, CDKN2B rs2069426 was more likely to develop lymph node metastasis (P = 0.017). The level of PD-L1 in the serum of ALL children was significantly higher than that of the control group, and there was no significant difference in PD-1 (P < 0.001). Additionally, children with CDKN2A rs3088440 had reduced CD8+ T cell counts than the wild group (P = 0.039).ConclusionCDKN2A rs3088440 and CDKN2B rs2069426 may be related to the occurrence and development of ALL in Chinese children. Additionally, PD-1/PD-L1 may be involved in the immune escape process of ALL, which is expected to become a new target for the treatment of the disease.

Significance of the Surgical Treatment with Lymph Node Dissection for Neuroendocrine Tumors of Thymus.

Neuroendocrine tumors of a thymus (NETTs) are rare, accounting for approximately 2-5% of all thymic epithelial tumors, and have a poor prognosis due to frequent lymph nodes or distant metastasis. We retrospectively reviewed the clinicopathological background and outcomes of 40 patients who underwent resection or surgical biopsy with histologically diagnosed NETTs from 1986 to 2022. The most common pathological type was atypical carcinoid. Surgical resection was performed in 35 patients, with lymph node dissection in 33 and surgical biopsy in five. The overall survival (OS) rate for all patients was 81.4% and 52.3% at 5 and 10 years, respectively. The 2-year survival rate was 20% for the biopsy group, which was significantly worse than that of the resected group (p < 0.001). The relapse-free survival rates were 61.7% and 37.6% at 5 and 10 years, respectively, in 34 patients with complete resection. The univariate analysis revealed better the OS rate in the resected cases but with no significant differences between histological grade, lymph node metastasis, tumor size, or Ki67 index. Surgical complete resection is considered to improve prognosis regardless of histologic type. NETTs frequently develop lymph node metastasis, thus, lymph node dissection seems necessary for complete resection.

Low-grade adenosquamous carcinoma of the breast: aclinical, morphological and immunohistochemical analysisof 25 patients.

Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management. Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months. LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.

Factors affecting prognosis in canine subcutaneous mast cell tumors: 45 cases.

To evaluate the clinical outcome of subcutaneous mast cell tumors (SQMCT) and to identify clinical and histological characteristics of more aggressive disease. Retrospective study. Forty-five dogs with 48 SQMCTs. Medical records were reviewed (2011-2021) for patient information, clinical, and histopathological data including multinucleation, necrosis, invasion into local muscle, an infiltrative growth pattern, tumor grade (if listed), mitotic index, and surgical margins. The presence of local recurrence, lymph node metastasis, survival time, and other parameters evaluating patient outcome were also recorded. Local recurrence occurred in 17.8% (8/45) of dogs, 11.1% (5/45) developed metastatic recurrence, and 26.7% (12/45) developed lymph node metastasis. Dogs with lymph node metastases had a median disease-free interval (DFI) of 194 days (18-1864), while median DFI was not reached for dogs without lymph node metastasis (p=.0012). Median survival time for dogs with lymph node metastasis was 551 days (110-2050) compared to 1722 days (10-1722) without metastasis (p=.0432). Local recurrence resulted in a significantly shorter median survival time of 551 days (80-2050) compared to 1722 days (10-1722) for dogs without local recurrence (p=.0038). Dogs with infiltrative tumors had a median DFI of 268 days (3-1722) and DFI for dogs without an infiltrative pattern had not reached median at 1864 days (10-1864) (p=.011). Lymph node metastasis decreased disease-free interval and survival. Subcutaneous mast cell tumors may be a more aggressive disease than previously reported.

Lipid Handling Protein Gene Expression in Colorectal Cancer: CD36 and Targeting miRNAs

The reprogramming of lipid metabolism has been highlighted in colorectal cancer (CRC) studies, suggesting a critical role for the scavenger receptor CD36 and fatty acid synthase (FASN) in this malignancy. In this study, we analyzed the gene expression levels of CD36, FASN, the cell surface glypican 4 (GPC4), and the two transporters SLC27A3 and SLC27A4 in 39 paired tumoral and peritumoral tissues from patients with CRC compared with 18 normal colonic mucosae. Moreover, the levels of seven miRNAs targeting CD36 and most of the analyzed genes were evaluated. We found a significant impairment of the expression of all the analyzed genes except GPC4 as well as the differential expression of miR-16-5p, miR-26b-5p, miR-107, miR-195-5p, and miR-27a-3p in the colonic mucosa of CRC patients. Interestingly, CD36 and miR-27a-3p were downregulated and upregulated, respectively, in tumoral tissues compared to peritumoral and control tissues, with a significant negative correlation in the group of patients developing lymph node metastasis. Our results sustain the relationship between CRC and fatty acid metabolism and emphasize the importance of related miRNAs in developing new therapeutic strategies.

Early distinction of lymph node metastasis in patients with soft tissue sarcoma and individualized survival prediction using the online available nomograms: A population-based analysis.

The presence of metastatic tumor cells in regional lymph nodes is considered as a significant indicator for inferior prognosis. This study aimed to construct some predictive models to quantify the probability of lymph node metastasis (LNM) and survival rate of patients with soft tissue sarcoma (STS) with LNM. Research data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2017, and data of patients with STS from our medical institution were collected to form an external testing set. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors for developing LNM. On the basis of the identified variables, we developed a diagnostic nomogram to predict the risk of LNM in patients with STS. Those patients with STS presenting with LNM were retrieved to build a cohort for identifying the independent prognostic factors through univariate and multivariate Cox regression analysis. Then, two nomograms incorporating the independent prognostic predictors were developed to predict the overall survival (OS) and cancer-specific survival (CSS) for patients with STS with LNM. Kaplan-Meier (K-M) survival analysis was conducted to study the survival difference. Moreover, validations of these nomograms were performed by the receiver operating characteristic curves, the area under the curve, calibration curves, and the decision curve analysis (DCA). A total of 16,601 patients with STS from the SEER database were enrolled in our study, of which 659 (3.97%) had LNM at the initial diagnosis. K-M survival analysis indicated that patients with LNM had poorer survival rate. Sex, histology, primary site, grade, M stage, and T stage were found to be independently related with development of LNM in patients with STS. Age, grade, histology, M stage, T stage, chemotherapy, radiotherapy, and surgery were identified as the independent prognostic factors for OS of patients with STS with LNM, and age, grade, M stage, T stage, radiotherapy, and surgery were determined as the independent prognostic factors for CSS. Subsequently, we constructed three nomograms, and their online versions are as follows: https://tyxupup.shinyapps.io/probabilityofLNMforSTSpatients/, https://tyxupup.shinyapps.io/OSofSTSpatientswithLNM/, and https://tyxupup.shinyapps.io/CSSofSTSpatientswithLNM/. The areas under the curve (AUCs) of diagnostic nomogram were 0.839 in the training set, 0.811 in the testing set, and 0.852 in the external testing set. For prognostic nomograms, the AUCs of 24-, 36-, and 48-month OS were 0.820, 0.794, and 0.792 in the training set and 0.759, 0.728, and 0.775 in the testing set, respectively; the AUCs of 24-, 36-, and 48-month CSS were 0.793, 0.777, and 0.775 in the training set and 0.775, 0.744, and 0.738 in the testing set, respectively. Furthermore, calibration curves suggested that the predicted values were consistent with the actual values. For the DCA, our nomograms showed a superior net benefit across a wider scale of threshold probabilities for the prediction of risk and survival rate for patients with STS withLNM. These newly proposed nomograms promise to be useful tools in predicting the risk of LNM for patients with STS and individualized survival prediction for patients with STS with LNM, which may help to guide clinical practice.

Oncologic outcomes of calcitonin-negative medullary thyroid carcinoma.

Calcitonin (Ct)-negative medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. This study aimed to clarify its incidence, clinicopathologic characteristics, management, and treatment outcome. We retrospectively analyzed data of patients with primary MTC. Patients were divided into two groups according to the preoperative serum Ct level (Ct-negative and Ct-positive). The demographic, pathologic, and molecular characteristics, and treatment outcomes were compared between the two groups. In the Ct-negative group, we analyzed the association between the operation type and treatment outcome. Of the total 312 patients, 24 were diagnosed with Ct-negative MTC. The rate of lymph node metastasis was significantly higher in the Ct-positive than in the Ct-negative group (47.9% vs. 0%, p<0.001). The proportion of patients with Ki-67 ≤10% was significantly higher in the Ct-negative than in the Ct-positive group (87.5% vs. 38.2%, p<0.001). Excellent response was achieved by 91.7% and 34.7% of patients in the Ct-negative and Ct-positive groups, respectively (p<0.001). In the Ct-negative group, excellent response was achieved by all female patients, but only 50% of male patients. Ct-negative MTC is rare and unlikely to develop lymph node metastasis. Unilateral lobectomy tends to provide a satisfactory chance of excellent response; however, this requires further validation.

Prognostic impact of number of examined lymph nodes on survival of patients with appendiceal neuroendocrine tumors.

The prognosis of patients with appendiceal neuroendocrine tumors (ANETs) is related to lymph node (LN) metastasis and other factors. However, it is unclear how the number of examined LNs (ELNs) impact on survival. To determine the factors affecting the cancer-specific survival (CSS) of patients with ANET and to evaluate the impact of the number of ELNs on survival. A total of 4583 ANET patients were analyzed in the Surveillance, Epidemiology, and End Results database. Univariate survival analysis was used to identify factors related to survival and the optimal number of ELNs and lymph node ratio (LNR) were determined by the Kaplan-Meier method. The survival difference was determined by CSS. Except for sex, the other factors, such as age, year, race, grade, histological type, stage, tumor size, ELNs, LNR, and surgery type, were associated with prognosis. The 3-, 5-, and 10-year CSS rates of ANET patients were 91.2%, 87.5, and 81.7%, respectively (median follow-up period of 31 mo and range of 0-499 mo). There was no survival difference between the two surgery types, namely, local resection and colectomy or greater, in both stratifications of tumor size ≥ 2 cm (P = 0.523) and < 2 cm (P = 0.068). In contrast to patients with a tumor size < 2 cm, those with a tumor size ≥ 2 cm were more likely to have LN metastasis (χ 2 = 378.16, P < 0.001). The optimal number of ELNs was more than 11, 7, and 18 for all patients, node-negative patients, and node-positive patients, respectively. CSS rates of patients with a larger number of ELNs were significantly improved (≤ 10 vs ≥ 11, χ 2 = 20.303, P < 0.001; ≤ 6 vs ≥ 7, χ 2 = 11.569, P < 0.001; ≤ 17 vs ≥ 18, χ 2 = 21.990, P < 0.001; respectively). ANET patients with an LNR value ≤ 0.16 were more likely to have better survival than those with values of 0.17-0.48 (χ 2 = 48.243, P < 0.001) and 0.49-1 (χ 2 = 168.485, P < 0.001). ANET ≥ 2 cm are more likely to develop LN metastasis. At least 11 ELNs are required to better evaluate the prognosis. For patients with positive LN metastasis, 18 or more LNs need to be detected and lower LNR values (LNR ≤ 0.16) indicate a better survival prognosis.

Translational Value of Tumor-Associated Lymphangiogenesis in Cholangiocarcinoma.

The prognosis of cholangiocarcinoma remains poor in spite of the advances in immunotherapy and molecular profiling, which has led to the identification of several targetable genetic alterations. Surgical procedures, including both liver resection and liver transplantation, still represent the treatment with the best curative potential, though the outcomes are significantly compromised by the early development of lymph node metastases. Progression of lymphatic metastasis from the primary tumor to tumor-draining lymph nodes is mediated by tumor-associated lymphangiogenesis, a topic largely overlooked until recently. Recent findings highlight tumor-associated lymphangiogenesis as paradigmatic of the role played by the tumor microenvironment in sustaining cholangiocarcinoma invasiveness and progression. This study reviews the current knowledge about the intercellular signaling and molecular mechanism of tumor-associated lymphangiogenesis in cholangiocarcinoma in the hope of identifying novel therapeutic targets to halt a process that often limits the success of the few available treatments.

Male Gender Is Associated with Lymph Node Metastasis but Not with Recurrence in Papillary Thyroid Carcinoma.

Background The incidence of papillary thyroid carcinoma (PTC) is higher in females than in males, but it remains unclear whether gender is associated with the aggressiveness of this disease. We aimed to clarify the influence of gender on the risk of developing lymph node metastasis (LNM) and on the prognosis of PTC patients. Study Design. Retrospective cohort study. Setting. Academic tertiary care center. Methods Clinical data of PTC patients who were admitted to the Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, between January 2013 and December 2018 were retrospectively reviewed. The differences in clinical features and outcomes between female and male patients were compared. Univariate and multivariate logistic regression analyses were conducted to assess the impact of gender on LNM. Kaplan–Meier curves were used to estimate recurrence-free survival (RFS). Results A total of consecutive 2536 patients were enrolled in this study. Males accounted for 25.2% (639 cases) of all patients. Central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) rates were 52.5% (1346/2536) and 22.0% (558/2536), respectively. Male presented with higher LNM rates than female patients (65.7% vs. 51.2%; P < 0.001). Male gender was independently associated with LNM (OR = 1.93, 95% CI: 1.59–2.35; P < 0.001). After full adjustment, male gender still remained significantly associated with CLNM in all subgroups; however, subgroup analyses indicated no significant relationship between gender and LLNM. In addition, after a median follow-up period of 30 months, no significant difference was found in RFS between female and male patients (P=0.15). Conclusions This observational cohort study revealed that male gender was significantly associated with CLNM; whereas, LLNM was not different between female and male PTC patients in southwestern China. Moreover, currently, there is insufficient evidence to justify that male gender is an independent prognostic factor for recurrence.

DENEB: Development of new criteria for curability after local excision of pathological T1 colorectal cancer using liquid biopsy.

According to the current international guidelines, high‐risk patients diagnosed with pathological T1 (pT1) colorectal cancer (CRC) who underwent complete local resection but may have risk of developing lymph node metastasis (LNM) are recommended additional intestinal resection with lymph node dissection. However, around 90% of the patients without LNM are exposed to the risk of being overtreated due to the insufficient pathological criteria for risk stratification of LNM. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for molecular residual disease and relapse detection after treatments including surgical and endoscopic resection of solid tumors. The CIRCULATE‐Japan project includes a large‐scale patient‐screening registry of the GALAXY study to track ctDNA status of patients with stage II to IV or recurrent CRC that can be completely resected. Based on the CIRCULATE‐Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for LNM. The aim of this study is to explore the ability of predicting LNM using ctDNA analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for CRC patients.

Assessment of Radiofrequency Ablation for Papillary Microcarcinoma of the Thyroid

Papillary microcarcinomas of the thyroid (mPTCs) account for an increasing proportion of thyroid cancers in past decades. The use of radiofrequency ablation (RFA) has been investigated as an alternative to surgery. The effectiveness and safety of RFA has yet to be determined. To evaluate the effectiveness and safety of RFA for low-risk mPTC. Embase, MEDLINE via Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched from inception to May 28, 2021. Articles reporting on adult patients with mPTC treated with RFA were included. Studies that involved patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension were excluded. Final article selection was conducted by multiple reviewers based on consensus. The proportion of eligible articles was 1%. This meta-analysis was conducted in accordance with the MOOSE guidelines. Random and fixed-effect models were applied to obtain pooled proportions and 95% CIs. The primary outcome was the complete disappearance rate of mPTC. Secondary outcomes were tumor progression and complications. Fifteen studies were included in this meta-analysis. A total of 1770 patients (1379 women [77.9%]; mean [SD] age, 45.4 [11.4] years; age range, 42.5-66.0 years) with 1822 tumors were treated with RFA; 49 tumors underwent 1 additional RFA session and 1 tumor underwent 2 additional RFA sessions. Mean (SD) follow-up time was 33.0 (11.4) months (range, 6-131 months). The pooled complete disappearance rate at the end of follow-up was 79% (95% CI, 65%-94%). The overall tumor progression rate was 1.5% (n = 26 patients), local residual mPTC in the ablation area was found in 7 tumors (0.4%), new mPTC in the thyroid was found in 15 patients (0.9%), and 4 patients (0.2%) developed lymph node metastases during follow-up. No distant metastases were detected. Three major complications occurred (2 voice changes lasting >2 months and 1 cardiac arrhythmia). Minor complications were described in 45 patients. The findings of this systematic review and meta-analysis suggest that RFA is a safe and efficient method to treat selected low-risk mPTCs. Radiofrequency ablation could be envisioned as step-up treatment after local tumor growth under active surveillance for an mPTC or initial treatment in patients with mPTCs with anxiety about active surveillance.

Preoperative prediction for lymph node metastasis in early gastric cancer by interpretable machine learning models: A multicenter study

BackgroundThe presence of lymph node metastasis plays a decisive role in the selection of treatment options in patients with early gastric cancer. However, there is currently no established protocol to predict the risk of lymph node metastasis before/after endoscopic resection. The aim of this study was to develop and validate several machine learning algorithms for clinical practice. MethodsA total of 2,348 patients with early gastric cancer were selected from 5 major tertiary medical centers. We applied 6 machine learning algorithms to develop lymph node metastasis prediction models for clinical feature variables. The partial dependence plots were used to explain the prediction of the models. The area under the receiver operating characteristic curve and area under the precision recall curve were measured to assess the detection performance. The R shiny interactive web application was used to translate the prediction model in a clinical setting. ResultsThe incidence of lymph node metastasis in patients with early gastric cancer was 13.63% (320/2348) and significantly higher in young women, in the lower third of the stomach, with a size >2 cm, depressed type, poorly/nondifferentiated, lymphovascular invasion, nerve invasion, and submucosal infiltration. In terms of age, there is a nonlinear and younger trend. XGBOOST displayed the best predictive performance at the initial and postendoscopy evaluation. In addition, the machine learning algorithm was converted to a user-friendly web tool for patients and clinicians. ConclusionXGBOOST can predict the risk of lymph node metastasis with best accuracy in patients with early gastric cancer. Our online web application may help determine the optimal best surgical option for patients with early gastric cancer.