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To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases in men with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients between November 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classified into 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymph node (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and liver metastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane (below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostate cancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showed that patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, and patients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those in G5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015; median OS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC, and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicate that the farther the NRLNs are located, the more aggressive the disease is.

Pediatric salivary gland cancer (SGC) is a rare occurrence, prompting our aim to scrutinize the prognostic implications of diverse neck evaluation methodologies. Pediatric patients diagnosed with SGC were retrospectively identified from the SEER database. The evaluation of lymph node (LN) status encompassed the 8 th AJCC neck staging system, in addition to analyzing the quantity and proportion of metastatic LNs. Prognostic impacts were assessed utilizing Cox proportional hazards models. The study cohort comprised 274 patients, with 41 exhibiting LN metastasis. Neck stage distribution revealed N1 in 23 patients (8.4%), N2 in 14 patients (5.1%), and N3 in 4 patients (1.5%). Notably, 17 cases (6.2%) manifested two or more metastatic LNs. The median ratio of positive to total LNs was calculated at 0.1212. In comparison to N0 stage classification, a significantly elevated risk of mortality was associated with N2 stage rather than N1 or N3 distinctions. Patients with one positive LN paralleled those devoid of LN metastasis in terms of survival outcomes. Conversely, the presence of two or more metastatic LNs markedly correlated with an inferior prognosis. Individuals with a ratio exceeding 0.1212 demonstrated an almost twofold higher risk of mortality relative to those with a ratio of ≤ 0.1212. The assessment of the number and ratio of positive LNs, as opposed to the traditional AJCC neck stage categorization, yields a more refined stratification of survival outcomes in pediatric SGC.

Indocyanine green (ICG) has been used to detect several types of tumors; however, its ability to detect metastatic lymph nodes (LNs) remains unclear. Our goal was to determine the feasibility of ICG in detecting metastatic LNs. We established a mouse model and evaluated the potential of ICG. The feasibility of detecting metastatic LNs was also evaluated in patients with lung or esophageal cancer, detected with computed tomography (CT) or positron-emission tomography (PET)/CT, and scheduled to undergo surgical resection. Tumors and metastatic LNs were successfully detected in the mice. In the clinical study, the efficacy of ICG was evaluated in 15 tumors and fifty-four LNs with suspected metastasis or anatomically key regional LNs. All 15 tumors were successfully detected. Among the fifty-four LNs, eleven were pathologically confirmed to have metastasis; all eleven were detected in ICG fluorescence imaging, with five in CT and seven in PET/CT. Furthermore, thirty-four LNs with no signals were pathologically confirmed as nonmetastatic. Intravenous injection of ICG may be a useful tool to detect metastatic LNs and tumors. However, ICG is not a targeting agent, and its relatively low fluorescence makes it difficult to use to detect tumors in vivo. Therefore, further studies are needed to develop contrast agents and devices that produce increased fluorescence signals.

Background The prognostic value of metastatic lymph node ratio (LNR) is still controversial in esophageal cancer. Aim This study aimed to compare the impact of AJCC N staging system (pN) and LNR on the prediction of long-term survival of patients with esophageal carcinoma. Methods A total of 496 patients were retrospectively analyzed who underwent esophageal resection at Henan Tumor Hospital from January 2006 to December 2010. The Kaplan–Meier method and log-rank test were used to estimate survival curves. Univariate and multivariate analyses were performed to compare prognostic factors for long-term survival. The difference between pN and LNR with overall survival (OS) was compared by receiver operating characteristic (ROC) curve and area under the curve (AUC). Results The 1-, 3-, 5-year overall survival rates of 496 patients were 73.6, 47.1 and 34.2 %, respectively. Univariate analyses showed that diseased region, tumor length, depth of tumor invasion, pN and LNR affected the prognosis, and multivariate analyses demonstrated that depth of tumor invasion, pN and LNR were independent risk factors. Among the three significant variables verified by multivariate analyses, LNR was the best for inadequately staged patients (<12 examined LNs). ROC analyses showed that compared with pN (AUC = 0.579, p  = 0.037), LNR (AUC = 0.680, p  = 0.002) had better predictive value ( z  = 2.275, p  = 0.029). Conclusions LNR has greater prognostic value than pN for esophageal squamous cell carcinoma, especially for patients with <12 LNs removed.

Background Neoadjuvant chemoradiotherapy (NCRT) is recommended as the treatment standard for locally advanced esophageal squamous cell carcinoma (ESCC). The use of immunotherapy in the neoadjuvant setting has gained attention. Multiple, clinical trials have explored the efficacy and safety of neoadjuvant immunochemotherapy (NICT). We evaluated the differences in clinicopathologic outcomes and the patterns of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT), NCRT, and NICT before esophagectomy for locally advanced ESCC. Methods A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy were included. Pathological characteristics, including pathologic complete response (pCR), tumor regression grade (TRG) score and patterns of lymphatic spread, were evaluated. Results Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response ( P  < 0.05). The pCR rate was 8.1% in the NCT group, 29.9% in the NCRT group, and 23.6% in the NICT group. The TRG score ( P  < 0.05) and pathologic T stage ( P  < 0.05) in the NCT group were significantly higher. Compared with NICT, NCRT can significantly reduce the rate of lymph node metastasis rate in station 1R (0 vs. 3.4%, P  < 0.05) and 2R (1.1% vs. 6.8%, P  < 0.05). Subgroup analysis according to the tumor location distribution showed that NICT group had higher lymph node metastasis rate in station 2R (9.1%) in middle thoracic cases ( P  < 0.05) and in station 18 (7.5%) ( P  < 0.05) in lower thoracic cases. Conclusions NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. For patients with lymph node metastasis in station 1R and 2R, NCRT should be the optimal preoperative treatment strategy.

Lymph node metastasis, the initial step in distant metastasis, represents a primary contributor to mortality in patients diagnosed with oral squamous cell carcinoma (OSCC). However, the underlying mechanisms of lymph node metastasis in OSCC remain incompletely understood. Here, the transcriptomes of 56 383 single cells derived from paired tissues of six OSCC patients are analyzed. This study founds that CXCR4+ epithelial cells, identified as highly malignant disseminated tumor cells (DTCs), exhibited a propensity for lymph node metastasis. Importantly, a distinct subset of tumor‐associated macrophages (TAMs) characterized by exclusive expression of phosphoprotein 1 (SPP1) is discovered. These TAMs may remodel the metastatic lymph node microenvironment by potentially activating fibroblasts and promoting T cell exhaustion through SPP1‐CD44 and CD155‐CD226 ligand‐receptor interactions, thereby facilitating colonization and proliferation of disseminated tumor cells. The research advanced the mechanistic understanding of metastatic tumor microenvironment (TME) and provided a foundation for the development of personalized treatments for OSCC patients with metastasis. SPP1+ TAMs are significantly enriched in metastatic lymph nodes of oral squamous cell carcinoma (OSCC), and it regulates the clonal colonization of CXCR4+ malignant epithelial cells by reshaping the metastatic microenvironment.

BackgroundThe metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined.MethodsFrom January 2007 to January 2018, 144 advanced GBC patients (T2–4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS).ResultsThe optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195–2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463–0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148–2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589–0.892) were independent prognostic factors for GBC (all P<0.05).ConclusionsLNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved.

Current surgical treatment for oral squamous cell carcinoma (OSCC) must be as precise as possible to fully resect tumors and preserve functional tissues. Thus, it is urgent to develop efficient fluorescent probes to clearly identify tumor delineation, as well as metastatic lymph nodes. Chemo-photothermal therapy combination attracted a growing attention to increase anti-tumor effect in various types of cancer, including OSCC. In the present study, we designed a multimodal NIR-II probe that involves combining photothermal therapy with chemotherapy, imaging OSCC tumors and detecting metastatic lymph nodes. : In this study, we synthesized a novel near infrared (NIR)-II probe named TQTPA [4,4'-((6,7-bis(4-(hexyloxy)phenyl)-[1,2,5]thiadiazolo [3,4-g]quinoxaline-4,9-diyl)bis(thiophene-5,2-diyl))bis(N,N-diphenylaniline)] via the Suzuki reaction and prepared multimodal nanoparticles (NPs) loading TQTPA and -dichlorodiammine platinum (CDDP) (HT@CDDP) by hyaluronic acid. The characteristics of the NPs, including their photothermal and imaging capabilities were investigated and . Their anti-tumor efficacy was evaluated using orthotopic, tongue tumor-bearing, nude mice. : The NPs possessed good stability and water solubility and were pH/hyaluronidase sensitive. The good tissue penetration quality and active targeting ability enabled the NPs to draw the outline of orthotopic tongue tumors and metastatic lymph nodes as small as 1 mm in nude mice by IR-808 under NIR exposure. and experiments validated the biocompatibility and low systematic toxicity of the NPs. At the same time, the NPs acted as multimodal therapy agents, combining photothermal therapy with chemotherapy. : With a good imaging capability and anti-tumor efficacy, our NPs successfully outlined orthotopic tongue tumors and metastatic lymph nodes as well as enabled chemo-photothermal therapy combination. Our study established a solid foundation for the application of new clinical diagnosis and treatment patterns in the future.

Purpose The Ki67 index and lymph node ratio (LNR) have been proposed as components of alternative pathological classification schemes, but the most appropriate classification for patients with medullary thyroid cancer (MTC) remains unknown. The aim of the present study was to examine the usefulness of a new grading system combining the Ki67 index and LNR as a predictor of prognostic and disease-free survival (DFS) in MTC. Methods We conducted a retrospective study of patients with MTC who were registered at Sun Yat-sen University Cancer Center, Guangzhou, P. R. China from June 2003 to October 2021. The DFS rates were assessed using risk-adjusted Cox proportional hazard regression modeling to explore the relationship among pathological features, nutritional status and DFS. The Ki67 index (cutoff value: 5% and 10%) and LNR (cutoff value: 0.2 and 0.3) were combined to create a new grading system. Results In total, 101 matched patients were assessed. The integrated grading system showed better separation of Kaplan Meier (KM) curves for DFS. As the grading stage progressed, there was a significant stepwise decrease in DFS, which was better than Ki67, LNR and N staging alone. According to the grading system, the high-risk group had a worse prognosis. Conclusion The proposed grading scheme demonstrated a better prognostic performance in MTC patients than the Ki67, LNR and N staging alone. However, larger scale studies are needed to further verify our findings.

Lymph node metastasis, the leading cause of mortality in esophageal squamous carcinoma (ESCC) with a highly complex tumor microenvironment, remains underexplored. Here, the transcriptomes of 85 263 single cells are analyzed from four ESCC patients with lymph node metastases. Strikingly, it is observed that the metastatic microenvironment undergoes the emergence or expansion of interferon induced IFIT3+ T, B cells, and immunosuppressive cells such as APOC1+APOE+ macrophages and myofibroblasts with highly expression of immunoglobulin genes (IGKC) and extracellular matrix component and matrix metallopeptidase genes. A poor‐prognostic epithelial‐immune dual expression program regulating immune effector processes, whose activity is significantly enhanced in metastatic malignant epithelial cells and enriched in CD74+CXCR4+ and major histocompatibility complex (MHC) class II genes upregulated malignant epithelia cells is discovered. Comparing with primary tumor, differential intercellular communications of metastatic ESCC microenvironment are revealed and furtherly validated via multiplexed immunofluorescence and immunohistochemistry staining, which mainly rely on the crosstalk of APOC1+APOE+ macrophages with tumor and stromal cell. The data highlight potential molecular mechanisms that shape the lymph‐node metastatic microenvironment and may inform drug discovery and the development of new strategies to target these prometastatic nontumor components for inhibiting tumor growth and overcoming metastasis to improve clinical outcomes. Here not only a high‐resolution landscape of the tumor, immune, and stromal compartments is provided in metastatic lymph node but also metastatic‐specific patterns comparing with primary tumor are highlighted, which provide insights that may help to shape the tumor microenvironment and inform the development of new strategies against these prometastatic nontumor components for inhibiting tumor growth and overcoming metastasis.