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Background The surgical protocols and prognosis of esophageal squamous cell carcinoma (ESCC) patients influenced by the status of lymph node metastasis. It is necessary to identify risk factors that can predict lymph node metastasis to assist in clinical treatment. Objective To investigate the predict value of tumor budding (TB) and tumor-infiltrating lymphocytes (TILs) on lymph node metastasis (LNM) in patients with ESCC. Methods A total of 124 patients with ESCC who underwent radical resection and retained paraffin-embedded specimens in the Affiliated People's Hospital of Ningbo University from January 2013 to March 2022 were selected as the research subjects. The light microscopy and CK5/6 immunohistochemical staining were used to evaluate the amount of TB and density of TILs. Multivariate Logistic regression analysis was used to explore the influencing factors of lymph node metastasis in patients with ESCC and the receiver operating characteristic (ROC) curve was plotted to investigate the predictive value of TB and TILs for lymph node metastasis in patients with ESCC. Results Multivariate Logistic regression analysis showed that TB〔OR=20.078, 95%CI (6.043, 66.713), P

The lymphatic system is a major gateway for tumor cell dissemination but the mechanisms of how tumor cells gain access to lymphatic vessels are not completely understood. Breast cancer cells undergoing epithelial-mesenchymal transition (EMT) gain invasive and migratory properties. Overexpression of the cytokine transforming growth factor β1 (TGFβ1), a potent inducer of EMT, is frequently detected in the tumor microenvironment and correlates with invasion and lymph metastasis. Recently, we reported that TGFβ1 stimulated breast cancer cells with mesenchymal properties to migrate in a targeted fashion towards the lymphatic system via CCR7/CCL21-mediated chemotaxis, similar to dendritic cells during inflammation. Here, we aimed to identify additional chemotactic factors and corresponding receptors that could be involved in guiding breast cancer cells through the lymphatic system. Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL7/IL7R and IL15/IL15R as pairs of chemokines and receptors with potential roles in promoting chemotactic migration of breast cancer cells with mesenchymal properties towards the lymphatics. The results demonstrate the capacity of TGFβ1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells and warrant further studies to explore the roles of IL7 and IL15 in promoting lymph metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

Background: The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods: One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results: The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion: Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer, characterized by a multifactorial etiology and high heterogeneity, continues to confound researchers in terms of its pathogenesis. Curcumin, a natural anticancer agent, exhibits therapeutic promise in gastric cancer. Its effects include promoting cell apoptosis, curtailing tumor angiogenesis, and enhancing sensitivity to radiation and chemotherapy. Long noncoding RNAs (lncRNAs) have garnered significant attention as biomarkers for early screening, diagnosis, treatment, and drug response because of their remarkable specificity and sensitivity. Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis, clinical staging, metastasis, drug sensitivity, and prognosis in gastric cancer. A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer development can provide novel insights for precision treatment and tailored management of patients with gastric cancer. This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregulating specific lncRNAs and modulating gastric cancer onset and progression., Aim: To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis, proliferation, and invasion. Furthermore, these findings were validated in clinical samples., Methods: The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation, flow cytometry to investigate its effects on apoptosis, and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells. Western blotting was used to gauge changes in the protein expression levels of CDK6, CDK4, Bax, Bcl-2, caspase-3, P65, and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment. Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in BGC-823 and MGC-803 cells. AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis, proliferation, migration, and invasion of gastric cancer cells. Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways. RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics., Results: Curcumin induced apoptosis and hindered proliferation, migration, and invasion of gastric cancer cells in a dose- and time-dependent manner. LncRNA AC022424.2 was upregulated after curcumin treatment, and its knockdown enhanced cancer cell aggressiveness. LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways. LncRNA AC022424.2 downregulation was correlated with lymph node metastasis, making it a potential diagnostic and prognostic marker., Conclusion: Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2. This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation. The results of this study enhance our understanding of gastric cancer development and precision treatment., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

• [68Ga]Ga-FAPI PET demonstrates superiority over [18F]FDG PET in the detection of lymph node metastases in various cancers, based on a comprehensive systematic review and meta-analysis. • No statistically significant difference is observed between [68Ga]Ga-FAPI PET and [18F]FDG PET for the detection of bone metastasis in the included studies. The aim of our meta-analysis and systematic review was to contrast the positivity rates of [68Ga]Ga-FAPI PET and [18F]FDG PET in detecting bone and lymph node metastases across diverse cancer types. We conducted a comprehensive search for eligible articles up until August 2023, utilizing databases including PubMed, Embase, and Web of Science. Studies focusing on the positivity rate of [68Ga]Ga-FAPI PET vs. [18F]FDG PET for bone and lymph metastasis were included. Using random-effect model, the positivity rate for [68Ga]Ga-FAPI PET and [18F]FDG PET were generated. In order to gauge the heterogeneity among aggregated studies, we utilized the I2 statistic. Additionally, we applied the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) methodology to evaluate the caliber of the studies encompassed in our analysis. A total of 430 publications were initially identified in the search. Eventually, 25 studies, involving 779 patients, met the inclusion criteria. In terms of bone metastasis, the findings indicate no statistically significant difference between the use of [68Ga]Ga-FAPI PET and [18F]FDG PET (P = 0.34). However, concerning lymph node metastasis, the results demonstrate significant difference between the two imaging agents (P = 0.04). This systematic review suggests that [68Ga]Ga-FAPI PET appears to outperform [18F]FDG PET in detecting lymph node metastases. However, when it comes to bone metastasis, no statistically significant difference was observed. It is crucial to acknowledge that the insights concerning bone metastasis stem from studies with comparatively modest sample sizes. Consequently, there is a pressing demand for further, expansive prospective studies in this field. [ABSTRACT FROM AUTHOR]

One of the main causes of local recurrence of rectal cancer is the regional lymphatic nodes metastasis. Existing methods of staging does not have absolute sensitivity and specificity with regard to lesion of regional lymphatic nodes in general, and of lateral group in particular. It is necessary to look for new methods of diagnosis, to identify risk factors and unfavorable prognosis of lateral metastasis in colorectal cancer, which will provide a more differentiated approach to the choice of treatment policy, indications for neoadjuvant chemoradiotherapy and/or lymphatic node dissection. The work on the two groups of patients (control and basic) was performed on the basis of CT performed in angio mode and MRI investigated anatomical variability of middle rectal arteries, proved its impermanence, and studied the relationship between presence of the middle rectal artery and lesion of regional lymphatic nodes in rectal cancer. Prognostic risk factors for lateral metastasis in rectal cancer were proposed, comparative analysis techniques allowing for visualization of the middle rectal vessels was performed.

It was already in the 18th century when the French surgeon LeDran first noted that breast cancer patients with spread of tumor cells to their axillary lymph nodes had a drastically worse prognosis than patients without spread (LeDran et al., ). Since then, metastatic spread of cancer cells to regional lymph nodes has been established as the most important prognostic factor in many types of cancer (Carter et al., ; Elston and Ellis, ). However, despite its clinical importance, lymph metastasis remains an underexplored area of tumor biology. Fundamental questions, such as when, how, and perhaps most importantly, why tumor cells disseminate through the lymphatic system, remain largely unanswered. Accordingly, no treatment strategies exist that specifically target lymph metastasis. The identification of epithelial-mesenchymal transition ( EMT) as a mechanism, which allows cancer cells to dedifferentiate and acquire enhanced migratory and invasive properties, has been a game changer in cancer research. Conceptually, EMT provides an explanation for why epithelial cancers with poor differentiation status are generally more aggressive and prone to metastasize than more differentiated cancers. Inflammatory cytokines, such as TGF-β, which are produced and secreted by tumor-infiltrating immune cells, are potent inducers of EMT. Thus, reactivation of EMT also links cancer-related inflammation to invasive and metastatic disease. Recently, we found that breast cancer cells undergoing TGF-β-induced EMT acquire properties of immune cells allowing them to disseminate in a targeted fashion through the lymphatic system similar to activated dendritic cells during inflammation. Here, we review our current understanding of the mechanisms by which cancer cells spread through the lymphatic system and the links to inflammation and the immune system. We also emphasize how imaging techniques have the potential to further expand our knowledge of the mechanisms of lymph metastasis, and how lymph nodes serve as an interface between cancer and the immune system. [ABSTRACT FROM AUTHOR]

The aim of our study was to develop a new score system that might predict the probability of lymph node of gastric carcinoma. We studied the clinicopathological variables of 932 patients with gastric carcinoma admitted to the Department of Surgical Oncology at the First Hospital of China Medical University. Logistic analysis was performed to identify predictors. The hazard risk (HR) of variables obtained from logistic regression was used to construct a simple scoring system determined by an aggregate of the points assigned for each selected variable. Receiver operator characteristic (ROC) curve was created to analyze the specificity. Lymph node metastases were found in 644 (69.1 %) of 932 patients. After multivariate logistic regression analysis, tumor size, depth of invasion, and macroscopic types ( P < 0.001) were selected as viable predictors to establish the scoring system. ROC curves were plotted to verify the accuracy of predicting score and other variables for both Lymph node stage (N stage) prediction. It showed that the predicting score system had a better specificity and sensitivity (65.71 % and 83.54 %, respectively). The current study suggests that a preoperative prediction system to identify the risk of lymph node metastasis is feasible. This model may be useful in preoperative counseling about the cost and benefit of systemic lymph node dissection. [ABSTRACT FROM AUTHOR]

Abstract: Active tumor targeting by biodegradable nanoparticles has been widely studied for cancer diagnosis and therapy. However, target-specific nanoparticles for drug delivery to lymphatic metastases have not been reported yet due to the lack of specific markers in the tumor lymphatics. Recently, peptide LyP-1 has been recognized for its specific home to tumors and their lymphatics. In this study, we tested the possibility of LyP-1 serving as a target-specific peptide of PEG–PLGA nanoparticles to tumor lymph metastases. LyP-1 was synthesized by using Boc-protected amino acids. The copolymers of maleimide–PEG–PLGA were formed by the conjugation of maleimide–PEG–NH2 to PLGA–COOH, which were applied to prepare pegylated nanoparticles with mPEG–PLGA by means of double emulsion/solvent evaporation technique. LyP-1 with sulfhydryl group was conjugated to the maleimide function located at the distal end of PEG surrounding the nanoparticle surface. LyP-1-conjugated PEG–PLGA nanoparticle (LyP-1-NPs) had a round and regular shape with a diameter around 90nm. In vitro, cellular uptake of LyP-1-NPs was about four times of that of PEG–PLGA nanoparticles without LyP-1 (NPs). In vivo, the uptake of LyP-1-NPs in metastasis lymph nodes was about eight times of that of NPs. This study indicates that LyP-1-NP is a promising carrier for target-specific drug delivery to lymphatic metastatic tumors. [Copyright &y& Elsevier]

Objective: To investigate the relationship between c-met expression with the node ratio lymph (LNR) and prognostic in gastric cancer. Methods: Retrospective analysis the clinical date of 120 patients who diagnosed with cervical cancer from june 2005 to june 2010. A linear regression model was used to investigate the relationship between the clinical data and c-met expression, multivariate analysis was performed using cox proportional hazard regression model in forward stepwise. Results: 38 cases occurred end point events. C-met level was associated with preoperative CA-125, N stage, the depth of tumor invasion: the degree of tumor (P=0.013) and C-met (P =0.02). depth of tumor invasion (P=0.04) is an independent risk factor for cervical cancer patients with metastasis or recurrence. Conclusion: The expression of C-met in cervical cancer is positive independent risk factors in patients with cervical cancer metastasis and recurrence. [ABSTRACT FROM AUTHOR]

In this rare case of intrahepatic malignant mesothelioma with subsequent lymph node metastases, hepatic segmentectomy in combination with repeated lymphadenectomy resulted in prolonged survival, currently 37 months after initial diagnosis. Immunohistochemically, vascular endothelial growth factor receptor-1 expressing tumor cells were surrounded by a dense D 2–40-positive lymphangiovascular network, suggesting tumor induced lymphangiogenesis correlating to 2-deoxy-2[18F]fluoro- d-glucose-positron emission tomography/computed tomography-positive recurrent intraabdominal and intrathoracic lymphatic tumor spread. Therefore, extended lymphadenectomy during primary tumor resection and combined adjuvant chemotherapy with promising anticancer agents possessing antilymphangiogenic and antimetabolite properties should be considered to prolong survival in cases of extrathoracic malignant mesothelioma. Additionally, as shown in our case, individual operative concepts and (sometimes) multiple operations can be beneficial for highly selected patients. Importantly, a case-by-case optimized antitumor regimen requires interdisciplinary expertise and consensus of all involved faculties. [ABSTRACT FROM AUTHOR]

Clinicopathological study was given to 100 early gastric cancer cases. The cases included 50 intramucosal lesions (m-group) and 62 submucosal lesions (sm-group), and the share is 17% of whole cases treated surgically. The sex ratio is about 2:1 (male: female). According to the classification by location, the occurrence rate of lesion on anterior wall is 18.8%. This fact suggests the impotance of roentgenscopy by compression technique and double contrast in a prone position focussed on anterior wall. In addition, endoscopy is essential in order to detect minute cancers. The rates of metastasis of early gastric cancers is 2.4% of m-group and 16.1% of sm-group. No metastasis occurs in protruded or elevated type as far as cancer cells remain within the mucosa. Once cancer cells infiltrate into the submucosa, metastasis is oberserved in 36%. In the present cases, 9 (9%) out of 100 cases of early gastric cancers are the multiple cases. In order to avoid oversight of cancer foci, the portion of stomach to be remained after surgery should be throughly examined prior to operation and again under direct vision after gastric incision. [ABSTRACT FROM AUTHOR]

Lymphatic metastasis is a major determinant of the outcome of resected pancreatic cancer. Gemcitabine-based adjuvant chemotherapy can improve the outcome of resected pancreatic cancer. However, the efficacy of gemcitabine against pancreatic cancer stratified by nodal involvement is unclear. In this study, patients who had undergone curative resection of pancreatic adenocarcinoma (612 cases) were included. The efficacy of adjuvant gemcitabine-based regimen, stratified by nodal status (negative, positive) or N substage (N0, no nodal involvement; N1, 1-3-node involvement; N2, ≥4-node involvement), was examined. Both the node-negative (hazard ratio [HR] = 0.62, 95% confidence interval [CI], 0.44-0.87, P = .006) and node-positive subgroups (HR = 0.45, 95% CI, 0.33-0.62, P < .001) benefited from gemcitabine-based adjuvant chemotherapy. Patients with N0 (ie, the node-negative subgroup) or N1 (HR = 0.36, 95% CI, 0.25-0.52, P < .001) disease benefited from gemcitabine-based chemotherapy. However, patients with N2 tumors (HR = 0.95, 95% CI, 0.50-1.78, P = .867) had poor response to gemcitabine-based treatment. Therefore, we postulate that resected pancreatic cancer with N2 node involvement is refractory to gemcitabine-based adjuvant chemotherapy. A more intensive adjuvant regimen may be required for N2 subgroup patients.

Lymph metastasis is a vital pathway of cancer cell dissemination, and insidious lymph node metastasis increases the risk of distant cancer metastasis. Current therapies for lymph metastasis are largely restricted by limited targeting and penetration capacity. Herein, we report that an r9 cell-penetrating peptide-based cabazitaxel nanovehicle (r9-CN) displays prominent lymph metastasis targeting and deep penetration ability after intravenous injection for effective anti-metastasis therapy. Methods: The r9-CN and CN nanovehicles were prepared by thin film dispersion, using DSPE-PEG2000 as the nano-carrier material and cabazitaxel as the model drug to fabricate r9-modified nano-micelles by self-assembly. The morphology, size, and stability in physiological solutions of r9-CN and CN were characterized. The targeting, biodistribution, deep penetration, and therapeutic efficacy of r9-CN and CN were systematically explored in vitro and in vivo. Results: The r9-CN nanovehicle consists of homogeneous particles with a mean diameter of 13 nm and zeta potential of +0.75 mV. Compared with the nanovehicle lacking the r9 peptide (CN), r9-CN exhibits long retention and deep penetration in the tumor mass, and considerably enhances accumulation and flexible permeation in metastatic lymph nodes, thereby notably suppressing primary tumor growth, lymph node metastasis, and distant lung metastasis. Conclusion: The cumulative findings reveal that r9-CN offers a promising delivery platform, enabling efficient lymph metastasis targeting and deep penetration for effective anti-metastasis therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: To investigate the related factors of mucosal melanoma of head and neck with lymph node metastasis for early diagnosis and further treatments. Method: A retrospective analysis of 117 cases of head and neck mucosal malignant melanoma patients which received surgical treatment was performed. Eleven cases of patients with pathologically confirmed lymph node metastasis and 33 cases without lymph node metastasis (1∶3) were randomly selected to analyze. The related factors of lymph node metastasis of head and neck mucosal melanoma patients including age, gender, whether the existence of recurrence, bone invasion, lesion location were analyzed. The single factor and logistic regression analysis were performed, P <0.05 difference was statistically significant. Result: The lymph node metastasis rate of head and neck mucosal melanoma was 9.40%(11/117), the single factor analysis showed that there were 3 factors to be associated with lymph node metastasis, which was recurrence ( P =0.0000), bone invasion ( P =0.001), primary position ( P =0.007). Recurrence ( P =0.021) was a risk factor for lymph node metastasis according to the Logistic regression analysis, and the impact of bone invasion ( P =0.487) and primary location ( P =0.367) remained to be further explored. Conclusion: The patients of head and neck mucosal melanoma with the presence of recurrent usually accompanied by a further progression of the disease, such as lymph node metastasis, so for recurrent patients should pay special attention to the situation of lymph node and choose the reasonable treatment., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)