Node Metastasis Research Articles

Survival associated with the use of sentinel lymph node in addition to lymphadenectomy in early-stage cervical cancer treated with surgery alone: A sub-analysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

AimThe aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer. MethodsInternational, multicenter, retrospective study. Inclusion criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy (‘SLN’ group) or pelvic lymphadenectomy alone (‘non-SLN’ group). Results1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5–98.5 versus 92.0 %,95 %CI:90.0–94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8–99.9 versus 96.8 %,95 %CI:95.4–98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266–0.959, p = 0.037 and HR:2.703,95 %CI:1.389–5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039). ConclusionAdding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer.

Nodal Metastasis in Oral Squamous Cell Carcinoma: an Analysis of Risk Factors and Influence on Overall Survival

Introduction: Oral squamous cell carcinoma (OSCC) presents a high tendency of lymph node metastasis (LNM). Objective: Determine which risk factors play a significant role in metastasis to cervical lymph nodes and to evaluate the influence of nodal involvement on overall survival of patients with OSCC. Method: Medical records of 350 patients with OSCC were retrospectively reviewed. The data were analyzed using the chi-square, Fisher’s exact and log-rank Mantel Cox tests and multinomial and Cox logistic regression. Results: Of the 350 medical records evaluated, 251 reported N0, 75 N1, 16 N2 and 8 N3. Male gender, referrals from private health care providers, T3/4 stage and non-surgical treatments were associated with LNM. In multivariate analysis, men and T3/4 tumors were shown to be independent risk factors for LNM. The independent risk factors for survival were male gender, nodal involvement (p = 0.017) and non-surgical treatment. Conclusion: Male gender and T-stage are risk factors for LNM in patients with OSCC. Moreover, the presence of LNM and age >65 years are associated with poor overall survival.urvivor.

Prognostic significance of anatomic site-specific depth of invasion in oral squamous cell carcinoma - An eastern Indian multi-center study

A crucial parameter in determining the prognosis of oral cavity cancer is depth of invasion (DOI). This research aimed to correlate pathological DOI at different intra-oral anatomical sites for oral squamous cell carcinoma (OSCC) with the risk of regional lymph node metastasis (LNM). This study also investigated the correlation of 3-year overall survival (OS) and disease-specific survival (DSS) with tumor depth. DOI measurement of the primary tumor at different intra-oral anatomic sites of clinically node negative patients who underwent curative surgery with elective neck dissection (END) was carried out as per AJCC 8th Edition staging guidelines in 3 DOI groups of ≤5 mm(A), >5 to ≤10 mm(B) and >10 mm(C). Association of groupwise DOI values with histopathological parameters including LNM and 3 years survival was evaluated. Univariate and multivariate logistic regression analysis (Odds ratio (OR) = 1.1 95 % CI: 1.0–1.2, p < 0.05) showed DOI to be a significant predictor for sub-clinical nodal metastasis observed in 136/382 OSCC patients. Receiver operating curve suggested that at 5 mm DOI (4 mm for early-stage OSCC), the risk of occult LNM was >20 % for all intra-oral sites combined. DOI <5 mm group demonstrated a superior 3-year OS (OR = 19.8 % CI: 7.8–49.9) and DSS (OR = 14.7 % CI: 5.9–37.0). Thus, DOI is an independent predictor of nodal metastasis and has significant association with LNM, OS and DSS. Our findings suggest that a DOI of ≥4 mm is an accurate cut-off value for performing END in early-stage OSCC and > 5 mm for advanced cases across all evaluated oral anatomic sites.

ThP3.9 - Direct to PET-CT in oesophagogastric cancers: A pilot project at a tertiary upper gastrointestinal surgical referral centre

Abstract Background Oesophageal cancer contributes to 18% of cancer mortalities worldwide. The aim of this pilot project was to offer direct positron emission tomography- computed tomography (PET-CT) imaging and observe any differences in time to investigation and treatment in the cohorts. Methods Patients referred with a diagnosis of oesophageal cancer between 1st January 2022 to 31st December 2022 were included. Data was collected from the electronic patient record and retrospective analysis was performed using Microsoft Excel. Results A total of 189 patients with OG cancer were included. There were 89 local and 100 network patients. Median age was 71[range 37 – 93]. Locally male female ratio was 52:37 and in the network 73:27 [“p” 0.03]. Of 35 patients who had direct PET-CT (A) 31(88%) were local and 4(12%) from the network. Among 115 patients who had a CT followed by PET scan (B) 29(25%) were local and 86 (75%) from the network [ “p” 0.00001]. Waiting times were 27 days for a PET-CT as compared to 32 days for PET after CT scan [ “p” 0.09]. Reports were available in a median 4 days in group A compared to 3.5 days in group B [ “p” 0.66]. In group A 12 (35%) had metastases with nodal metastases in 9(75%) and distant metastases in 3(25%). Conclusion Whilst direct to PET-CT improved patient experience there were no statistically significant differences in the time to investigations and treatment. Three patients with distant metastases offered direct PET-CT could have been diagnosed by CT.

Artificial intelligence system for identification of overlooked lung metastasis in abdominopelvic computed tomography scans of patients with malignancy.

This study aimed to evaluate whether an artificial intelligence (AI) system can identify basal lung metastatic nodules examined using abdominopelvic computed tomography (CT) that were initially overlooked by radiologists. We retrospectively included abdominopelvic CT images with the following inclusion criteria: a) CT images from patients with solid organ malignancies between March 1 and March 31, 2019, in a single institution; and b) abdominal CT images interpreted as negative for basal lung metastases. Reference standards for diagnosis of lung metastases were confirmed by reviewing medical records and subsequent CT images. An AI system that could automatically detect lung nodules on CT images was applied retrospectively. A radiologist reviewed the AI detection results to classify them as lesions with the possibility of metastasis or clearly benign. The performance of the initial AI results and the radiologist's review of the AI results were evaluated using patient-level and lesion-level sensitivities, false-positive rates, and the number of false-positive lesions per patient. A total of 878 patients (580 men; mean age, 63 years) were included, with overlooked basal lung metastases confirmed in 13 patients (1.5%). The AI exhibited an area under the receiver operating characteristic curve value of 0.911 for the identification of overlooked basal lung metastases. Patient- and lesion-level sensitivities of the AI system ranged from 69.2% to 92.3% and 46.2% to 92.3%, respectively. After a radiologist reviewed the AI results, the sensitivity remained unchanged. The false-positive rate and number of false-positive lesions per patient ranged from 5.8% to 27.6% and 0.1% to 0.5%, respectively. Radiologist reviews significantly reduced the false-positive rate (2.4%-12.6%; all P values < 0.001) and the number of false-positive lesions detected per patient (0.03-0.20, respectively). The AI system could accurately identify basal lung metastases detected in abdominopelvic CT images that were overlooked by radiologists, suggesting its potential as a tool for radiologist interpretation. The AI system can identify missed basal lung lesions in abdominopelvic CT scans in patients with malignancy, providing feedback to radiologists, which can reduce the risk of missing basal lung metastasis.

Contralateral submental artery island flap for oral tongue reconstruction — a retrospective study in patients with oral tongue squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related death in developing countries. The oral tongue is the most common site involved by OSCC. About a third of the patients have neck nodal metastasis at presentation. Reconstruction of the oral tongue after resection for cancer is necessary for proper rehabilitation. For patients who are medically unfit for prolonged surgery like a free tissue transfer, local flaps are employed for tongue reconstruction. The submental flap is a popular option. However, when there is extensive floor of mouth involvement or bulky nodal disease in ipsilateral level 1, harvesting the submental flap based on contralateral facial vessels is possible, without compromising oncological safety. We discuss the feasibility and outcomes of contralateral submental artery island flap for reconstruction after resection of oral tongue carcinoma in a retrospective series of 34 patients followed up for a median of 8.5 months. ResultsOf the 34 oral tongue cancer patients in the study, 16 had neoadjuvant chemotherapy prior to surgery. 33 underwent bilateral neck dissection. Two patients had partial flap loss which was managed conservatively. There were five patients who had either locoregional or distant recurrence, none in the flap site. Three had pathological positive nodes at contralateral level 1b and two had pathologically positive nodes in contralateral level 1b. Tongue motility and speech intelligibility were satisfactory on follow-up. ConclusionIn the properly selected patient, the contralateral submental artery island flap offers an oncologically safe and technically simpler alternative for free flap reconstruction.

Incidence of Colorectal Malignancy of a Young Patient in Sylhet M A G Osmani Medical College, Sylhet, Bangladesh

Background: Colorectal cancer is the third most common cancer in both men and women, and the second leading cause of cancer-related deaths. Colorectal cancer (CRC) is already the third leading cause of cancer death in the world, and its incidence is steadily rising in developing nations. Methods: A retrospective analytical study was conducted for newly diagnosed CRC patients treated in the Department of Surgery, Sylhet MAG Osmani Medical College, Sylhet, Bangladesh from January to June 2023. Convenient sampling method was followed to include 150 newly diagnosed young CRC patients registered. The study aimed to determine the burden of CRC among younger adults, and to evaluate its clinicopathological characteristics. Chi-square method was used to analyze the clinic pathological characteristics. P≤0.05 was considered statistically significant. Results: Out of total 150 newly diagnosed CRC patients. The median age at diagnosis was 54 years and 40 years for overall patients and younger adults respectively. Predominantly male patients were observed in the study population with male to female ratio (M: F) of 1.6:1. Most patients (approximately two third) presented with eastern co- operative oncology group (ECOG) performance status I. Family history of colorectal cancer or polyps was present in two patients, both of which belonged to the younger adults group. Greater than 90% of patients were diagnosed with advanced T stage (T3/T4) and over 80% patients had lymph nodal metastasis at diagnosis findings were age groups. Peritoneal metastasis was significantly higher among younger adults. Distant metastasis was observed in approximately one fourth of total patients, out of which majority (96%) were detected at multiple sites and numbers. Relatively higher number of distant metastasis was observed among younger patients. Common sites of distant metastasis were in the following order; liver&gt; peritoneum&gt; lung&gt; bone&gt; brain&gt; others. Peritoneal metastasis was found to be ..........

Comparative Performance of 68Ga-PSMA-11 PET/CT and Conventional Imaging in the Primary Staging of High-Risk Prostate Cancer Patients Who Are Candidates for Radical Prostatectomy.

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT's impact on patient management. Sixty castration-sensitive high-risk (ISUP 4-5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22-17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Lymph node evaluation and nodal metastasis prediction in epithelial ovarian cancers: A retrospective study.

To identify consensus regarding lymph node (LN) evaluation in epithelial ovarian cancer (EOC). The objective of the present study was to evaluate surgico-pathological findings, LN involvement, and the prediction of LN metastasis via preoperative imaging and intraoperative assessment in women with EOC. Women with EOC who underwent cytoreductive surgery (CRS) between Jan 2019 to June 2022 were included. The distribution of histology, stage, and LN metastasis was studied. The predictive value of serum cancer antigen (CA)-125, instead of and radiologically and surgically enlarged LNs with final LN histopathology was studied. A total of 96 women with EOCs underwent CRS. Fifty women (52%) underwent primary CRS and 46 women (48%) underwent interval CRS. Seventy-five women (78.13%) with EOC underwent pelvic and/or para-aortic lymphadenectomy, out of which 23 (30.67%) were histologically positive. High-grade serous carcinoma was the commonest (n=55, 73.33%) histology. The majority of women, 56 (74.67%) were stage III or IV at presentation. Complete cytoreduction was achieved in 59 (78.66%) patients. The receiver operating characteristics curve showed a cutoff for CA-125 of 1360 U/mL (area under the curve 0.702, p=0.002) for LN metastases. Both radiologically and surgically enlarged LNs significantly predicted LN metastasis on histopathology (p=0.02 and 0.006 respectively). The combined sensitivity, specificity, positive predictive value and negative predictive value of both contrast enhanced computed tomography (CECT) and surgically enlarged LNs were 78.26%, 57.69%, 45%, and 85.71%, respectively. Serous histology, high-grade tumors, highCA-125 levels, and suspicious LNs on CECT or during surgery were significantly associated with LN metastasis. However, considering the false-negative rate of 21.74%, the combination of radiologically and surgically enlarged LNs cannot be used as the sole surrogate marker for lymphadenectomy.

Advanced female urethral adenocarcinoma: A case report.

Urethral cancer in females is a rare occurrence. Although initially believed to be derived from skene glands, there is no consensus on the cell of origin. Squamous cell carcinoma is the most common, whereas adenocarcinoma is the least common. We report the case of a 58-years-old lady with a history of voiding lower urinary tract symptoms, later requiring a suprapubic cystostomy for retention. Cystoscopy and biopsy showed prostate-specific antigen (PSA) negative adenocarcinoma and postiron emission computed tomography (PETCT) showing pelvic and inguinal nodal metastasis. The patient underwent neoadjuvant chemotherapy followed by anterior exenteration with pelvic lymphadenectomy and ileal conduit. Final histology showed ypT4 yN1 adenocarcinoma, not otherwise specified.

399. LYMPH NODE METASTATIC PATTERNS AND SENTINEL LYMPH NODES FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER DIFFERENT NEOADJUVANT REGIMENS

Abstract Background This study aimed to outline lymph node metastasis patterns in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT), comparing regimens, assessing prognosis impact, and identifying potential sentinel lymph node stations for future individualized dissection. Methods Involving 578 ESCC patients undergoing nCRT (n=303) or nCT (n=275) followed by esophagectomy (2010-2022), we conducted propensity score matching, analyzing 171 pairs. Nodal metastasis patterns and station positivity associations with survival were assessed through univariate and multivariate models, adjusting for clinical factors. Results Among 171 nCRT patients, 36.8% had nodal metastases, 22.8% single-station, 8.2% two-station, and 5.8% ≥3-station occurrences. Specific station positivity correlated with poorer survival. The nCRT group had fewer nodal metastases (36.8% vs 50.3%), common sites being left gastric, right recurrent laryngeal nerve, and paraesophageal region. Increased nodal stations and positive nodes correlated with worse prognosis. In nCRT, mentioned areas were prognostic; in nCT, only left gastric nodal metastases were prognostic. Single and multi-station rates were similar, but nCT had more multi-station disease. For sentinel lymph nodes, positivity in left gastric, paraesophageal, right recurrent laryngeal nerve for nCRT, and subcarinal, left recurrent laryngeal nerve, paratracheal, left gastric, paraesophageal right recurrent laryngeal nerve for nCT, may indicate complex metastasis. Conclusions Over one-third of ESCC patients had post nCRT metastatic lymph nodes. Though nCRT reduced metastasis rates, survival outcomes didn't improve, emphasizing thorough lymph node dissection based on metastasis patterns.

49464 Use of Imaging in Cutaneous Squamous Cell Carcinoma to Detect High-Risk Tumor Features, Nodal Metastasis, and Distant Metastasis: A Systematic Review

49464 Use of Imaging in Cutaneous Squamous Cell Carcinoma to Detect High-Risk Tumor Features, Nodal Metastasis, and Distant Metastasis: A Systematic Review

Clinical impact of pancreatic invasion in T1-stage distal bile duct cancer and prognostic factors associated with long-term survival: A multicenter study.

The eighth edition of the AJCC staging system introduced a shift in the staging of distal bile duct cancer (DBC), emphasizing the depth of invasion over adjacent organ invasion. This study aimed to evaluate the clinical impact of pancreatic invasion in pT1-stage DBC and identify prognostic factors for long-term survival. This multicenter retrospective analysis encompassed DBC patients who underwent pancreaticoduodenectomy between 2009 and 2019 in six Korean tertiary centers, specifically those with final pathology confirming AJCC eighth edition T1 stage and intrapancreatic bile duct tumor origin. Primary endpoints were five-year recurrence-free survival (RFS) and overall survival (OS). Secondary objectives included the identification of prognostic determinants. This study involved 287 patients, comprising 190 without and 97 with pancreatic invasion. Pancreatic invasion did not significantly influence five-year OS and RFS rates (OS: without pancreatic invasion 69.9% vs. with pancreatic invasion 54.1%, p = .25; RFS: 56.3% vs. 55.4%, p = .97). Multivariate analysis highlighted male gender, age, lymphovascular invasion, and N stage as significant OS determinants. Notably, male gender, ampulla of Vater invasion, lymphovascular invasion, and N1 stage were also associated with RFS. In pT1 DBC, pancreatic invasion demonstrates no substantial impact on long-term prognosis, in accordance with the depth-based paradigm of the eighth edition AJCC staging system. The prognostic factors influencing OS were identified as male gender, age, lymphovascular invasion, and nodal metastasis.

Deep learning-based prediction of nodal metastasis in lung cancer using endobronchial ultrasound

ObjectiveEndobronchial ultrasound-guided transbronchial needle aspiration is a vital tool for mediastinal and hilar lymph node staging in patients with lung cancer. Despite its high diagnostic performance and safety, it has a limited negative predictive value. Our objective was to evaluate the diagnostic performance of deep learning-based prediction of lung cancer lymph node metastases using convolutional neural networks developed from automatically extracted images of endobronchial ultrasound videos without supervision of the lymph node location. MethodsPatient and lymph node data were collected from a single-center database. The diagnosis of metastasis was confirmed with endobronchial ultrasound-guided transbronchial needle aspiration and/or surgically resected specimens; the diagnosis of normal lymph node was confirmed with surgically resected specimens only. An annotation system facilitated automated image extraction from endobronchial ultrasound videos. Image frames were randomly selected and split into training and validation datasets on a per-patient basis. A deep learning model with convolutional neural networks, SqueezeNet, was used for image classification via transfer learning based on pretraining from ImageNet. Adaptive moment estimation and stochastic gradient descent were applied as optimizers. ResultsSqueezeNet, with adaptive moment estimation, achieved a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 96.7% each after 300 epochs, whereas SqueezeNet with stochastic gradient descent achieved 91.1% each. However, SqueezeNet with stochastic gradient descent demonstrated more stable performance than with adaptive moment estimation. ConclusionsDeep learning-based image classification using convolutional neural networks showed promising diagnostic accuracy for lung cancer nodal metastasis. Future clinical trials are warranted to validate the algorithm's efficacy in a prospective, large-cohort study.

53106 Primary cutaneous melanoma patients stratified by the Merlin assay (CP-GEP): risk of nodal metastasis and long-term survival outcome in a U.S. cohort

53106 Primary cutaneous melanoma patients stratified by the Merlin assay (CP-GEP): risk of nodal metastasis and long-term survival outcome in a U.S. cohort

Prognostic impact based on tumor diameter of pathological N1 lymph node metastases for non-small cell lung cancer.

The N parameter in the tumor-node-metastasis (TNM) classification of lung cancer is categorized according to the location of nodal metastasis, while that for some other cancers are classified according to the size and number of metastatic foci. In lung cancer, the impact of size of nodal metastasis on prognosis is unclear. This analysis aims to examine whether it is possible to subdivide the pathological N (pN) factor based on the tumor diameter of lymph node metastases. We studied 35 cases of adenocarcinoma and 26 cases of squamous cell carcinoma of the lung. The maximum diameter of lymph node metastasis was measured, and the relationship between the maximum diameter of lymph node metastases and prognosis was investigated. Squamous cell carcinoma cases had a significantly larger maximum tumor diameter of lymph node metastasis than adenocarcinoma cases (P=0.03). Based on receiver operating characteristic (ROC) curve results for the adenocarcinoma cases, we set 4 mm as a diameter cutoff value. The 5-year overall survival (OS) rate was 85.6% for patients with diameters ≤4 mm and 57.7% for those with diameters >4 mm; this difference was statistically significant (P=0.04). On univariate analysis using a Cox proportional hazards model, significant differences were observed in metastatic lymph node diameter (≤4 vs. >4 mm) (P=0.04), sex (P=0.04), and pathological T (pT) status (pT1 and 2 vs. pT3 and 4) (P=0.03). However, similar results were not obtained for patients with squamous cell carcinoma. The tumor diameter of pathological N1 lymph node metastases impacts the prognosis of patients with lung adenocarcinoma. If pathological N1 can be further subdivided according to tumor diameter of lymph node metastases, a more accurate prognosis may become possible. However, pathological type must be considered for staging in lung cancer. While the pN parameter for most cancers considers tumor size of lymph node metastasis, this does not apply to lung cancer.

18F-FDG, 68Ga-PSMA, and 64Cu-DOTATATE PET/CT—One Patient, Three Cancers

Abstract A 67-year-old man with a history of multiple myeloma, prostate cancer, and rectal carcinoid tumor underwent 18F-FDG PET/CT for surveillance, which revealed a non–FDG-avid lesion in the liver. To rule out metastasis from prostate cancer and carcinoid tumor, 68Ga-PSMA and 64Cu-DOTATATE PET/CT scans were ordered for respective malignancies. The 64Cu-DOTATATE scan showed radiotracer uptake in the hepatic lesion compatible with metastasis of the carcinoid tumor. Additionally, both 68Ga-PSMA and 64Cu-DOTATATE PET/CT scans revealed nodal metastasis within the pelvis. This case highlights the importance of appropriate radiotracer selection in conjunction with patient history in the evaluation of patients with multiple malignancies.

Dendritic Cell-Hitchhiking In Vivo for Vaccine Delivery to Lymph Nodes.

Therapeutic cancer vaccines are among the first FDA-approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph-node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated-DCs homing from the periphery to the LNs, an injectable hydrogel-based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine "hitchhiking" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve "antigen anchoring" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and "hitchhiking" subcutaneous Migrated-DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six-fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN-resident APCs via the "One-to-Many" strategy (One Migrated-DC corresponding to Many LN-resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation.

Tumor budding and complete epithelial mesenchymal transition correlate with late nodal metastasis in early-stage tongue squamous cell carcinoma

BackgroundLate nodal metastasis is a poor prognostic factor for early-stage tongue squamous cell carcinoma. However, for most early-stage patients, there is a low risk for late nodal metastasis, which currently lacks a diagnostic marker. Tumor budding is a nodal metastasis risk factor in other human cancers. Here, we evaluated tumor budding by partial or complete epithelial-mesenchymal transition and Ovol2 expression, a transcription factor that directly suppresses epithelial-mesenchymal transition. MethodsSixty-six T1–2N0 patients were enrolled in this retrospective study. Tumor expressions of E-cadherin and vimentin (epithelial-mesenchymal transition markers) and Ovol2 were assessed by immunohistochemistry. Tumor histopathological and immunohistochemical features, mode of invasion, and tumor budding were assessed. Correlations between these potential predictive factors and late nodal metastasis were determined statistically. ResultsUnivariate analysis demonstrated lymphoid infiltrate, perineural invasion, infiltrative growth pattern, tumor budding, vimentin positive, and complete epithelial-mesenchymal transition were significant factors of late nodal metastasis (all P < 0.05), observed in 25.8 % of patients. Multivariate analysis identified tumor budding and vimentin positive were independent prognostic factors (both P < 0.025). Ovol2 expression was significantly decreased in partial and complete epithelial-mesenchymal transition cells (both P < 0.01) compared with normal epithelia. Univariate analysis, but not multivariate analysis, showed Ovol2 correlated with depth of invasion and tumor budding (both P < 0.05). ConclusionTumor budding and vimentin expression are risk factors for late nodal metastasis in T1–2N0 tongue squamous cell carcinoma. Ovol2 might be involved in the early stages of epithelial-mesenchymal transition. Evaluation of these factors might identify patients susceptible to late nodal metastasis who require elective neck dissection.

Sequential Responsive Multifunctional Nanomicelle Effectuates Collective Elimination of Breast Cancer and Cancer Stem Cells.

Designing effective multifunctional nanodrugs to achieve multimodal treatment of tumors is an ideal choice to improve the poor clinical outcomes of current anti-tumor therapies. Here, a multifunctional nanomicelle DC@H loaded with sarcoma kinase and cyclooxygenase-2 protein dual target inhibitor DI02 is designed and prepared, which is sequentially catalyzed by carboxylesterase and glutathione for reduction, and strengthens the inhibition of cancer stem cell (CSC) related protein STAT3. The camptothecin carried by the DC@H ensures the effectiveness of chemotherapy. Ultimately, DC@H precisely releases and achieves effective inhibition of xenograft tumors based on the combination of chemotherapy, targeted therapy, and chemodynamic therapy, with a tumor inhibition rate of up to 90.89% in BALB/c nude mice. Research on lung metastasis proves that the CSC inhibitory characteristic of DC@H is a direct cause of the elimination of tumor metastatic nodules. There is no doubt that the multifunctional nano drug DC@H, which effectuates the collective elimination of breast cancer and cancer stem cells, provides a promising direction for achieving complete tumor cure in clinical practice.