Risk factors and impact of occult and skip metastasis in early-stage oral tongue squamous cell carcinoma.

OBJECTIVES: To investigate risk factors associated with occult lymph node metastases (ONM) and skip metastasis in early-stage oral tongue squamous cell carcinoma (OTSCC) patients. Meanwhile, to analyze the contribution of metastatic nodes to survival outcomes. MATERIALS AND METHODS: 544 OTSCC patients who were clinically staged T1-T2N0 with pathologic results from May 2018 to January 2024 were enrolled. Those with ONM were divided into subgroups with or without skip metastasis. Clinical, laboratorial, radiological and pathological factors between groups were analyzed by using univariate analysis and multivariate logistic analysis. The association of tumor growth behavior with the metastatic pattern of lymph nodes was summarized. Additionally, disease free survival (DFS) among different groups were compared using Kaplan-Meier analysis. RESULTS: Tumor growth behavior was associated with ONM. Tumor thickness with a threshold of 6.4 mm was not inferior to histological depth of invasion in predicting ONM. Only 1.3% of patients had nodal involvement of neck level IV or V. The DFS of patients with ONM were significantly reduced than those without ONM (P < 0.001). The DFS between patients with and without skip metastasis exhibited no statistical significance(P = 0.246). The 1-year, 2-year recurrence rates of patients with or without ONM were 31.9%, 37.5%, 10.1% and 14.0%, correspondingly. CONCLUSIONS: Tumor thickness with a threshold of 6.4 mm could be used as a preoperative predictor for ONM. Elective neck dissection of level I - III might be sufficient for early stage OTSCC patients. OTSCC patients with ONM should be closely observed during the first 2 years after surgery. CLINICAL RELEVANCE: The risk of ONM in early stage OTSCC patients might be predicted by tumor thickness calculated on MR imaging. Elective neck dissection of level I - III could remove micrometastases timely and effectively.

Long-term outcomes of sentinel lymph node navigation surgery for early-stage cervical cancer.

BACKGROUND: Sentinel lymph node navigation surgery, which identifies the sentinel lymph node in early cervical cancers and omits systemic pelvic lymphadenectomy in cases where no lymph node metastasis is present, has recently gained attention. However, there are few reports on lymph node recurrence and the long-term outcomes of cervical cancer surgery performed using sentinel lymph node navigation surgery. In this study, we aimed to evaluate the long-term outcomes of sentinel node navigation surgery for early-stage cervical cancer. METHODS: One hundred thirty-eight patients with cervical cancer were enrolled. Sentinel lymph nodes were identified by injecting 99 m Technetium-labeled phytate and indocyanine green into the uterine cervix. Surgery and survival outcomes were also analyzed. RESULTS: The median age and body mass index of the patients were 40 years (20-78) and 21.7 kg/m2 (16.5-50.4), respectively. Open surgery, laparoscopic surgery, and robotic surgery were performed in 77 (56%), 53 (38%), and 8 (6%) patients, respectively. The overall and bilateral detection rates of the sentinel lymph node were 100% and 94%, respectively. Only one case (0.7%) exhibited lower extremity lymphedema, and pelvic lymphocele was observed in three cases (2.2%). Four cases (3%) experienced recurrence over a median follow-up of 57.5 months (range, 2-115 months), with five-year recurrence-free and overall survival rates of 97% and 97.3%, respectively. CONCLUSIONS: Our results demonstrate that sentinel node navigation surgery may be safe and effective for early-stage cervical cancer.

Individualized prediction of non-sentinel lymph node metastasis in Chinese breast cancer patients with ≥ 3 positive sentinel lymph nodes based on machine-learning algorithms.

BACKGROUND: Axillary lymph node dissection (ALND) is a standard procedure for early-stage breast cancer (BC) patients with three or more positive sentinel lymph nodes (SLNs). However, ALND can lead to significant postoperative complications without always providing additional clinical benefits. This study aims to develop machine-learning (ML) models to predict non-sentinel lymph node (non-SLN) metastasis in Chinese BC patients with three or more positive SLNs, potentially allowing the omission of ALND. METHODS: Data from 2217 BC patients who underwent SLN biopsy at Shantou University Medical College were analyzed, with 634 having positive SLNs. Patients were categorized into those with ≤ 2 positive SLNs and those with ≥ 3 positive SLNs. We applied nine ML algorithms to predict non-SLN metastasis. Model performance was evaluated using ROC curves, precision-recall curves, and calibration curves. Decision Curve Analysis (DCA) assessed the clinical utility of the models. RESULTS: The RF model showed superior predictive performance, achieving an AUC of 0.987 in the training set and 0.828 in the validation set. Key predictive features included size of positive SLNs, tumor size, number of SLNs, and ER status. In external validation, the RF model achieved an AUC of 0.870, demonstrating robust predictive capabilities. CONCLUSION: The developed RF model accurately predicts non-SLN metastasis in BC patients with ≥ 3 positive SLNs, suggesting that ALND might be avoided in selected patients by applying additional axillary radiotherapy. This approach could reduce the incidence of postoperative complications and improve patient quality of life. Further validation in prospective clinical trials is warranted.

Predicting axillary lymph node metastasis in breast cancer based on ultrasound radiofrequency time-series analysis.

BACKGROUND: The status of axillary lymph nodes (ALN) plays a critical role in the management of patients with breast cancer. It is an urgent demand to develop highly accurate, non-invasive methods for predicting ALN status. PURPOSE: To evaluate the efficacy of ultrasound radiofrequency (URF) time-series parameters, in combination with clinical data, in predicting ALN metastasis in patients with breast cancer. MATERIAL AND METHODS: We prospectively gathered clinicopathologic and ultrasonic data from patients diagnosed with breast cancer. Various machine-learning (ML) models were developed using all available features to determine the most efficient diagnostic model. Subsequently, distinct prediction models were created using the optimal ML model, and their diagnostic performances were evaluated and compared. RESULTS: The study encompassed 240 patients, of whom 88 had lymph node metastases. A leave-one-out cross-validation (LOOCV) method was used to split the entire dataset into training and testing subsets. The random forest ML model outperformed the other algorithms, with an area under the curve (AUC) of 0.92. Prediction models based on clinical, ultrasonic, URF parameters, clinical + ultrasonic, clinical + URF, and ultrasonic + URF parameters had AUCs of 0.56, 0.79, 0.78, 0.90, 0.80, and 0.84, respectively, in the testing set. The comprehensive diagnostic model (clinical + ultrasonic + URF parameters) demonstrated strong diagnostic capability, with an AUC of 0.94 in the testing set, exceeding any single prediction model. CONCLUSION: The combined model (clinical + ultrasonic + URF parameters) could be used preoperatively to predict lymph node status, offering valuable input for the design of individualized surgical approaches.

Multidisciplinary Approach to Melanoma: A Case Report on Below-Knee Amputation and Lymph Node Dissection.

A 65-year-old male presented with progressive swelling and difficulty in walking due to a right foot sprain. Initial treatments were conducted in Chandrapur, followed by referral to Acharya Vinoba Bhave Rural Hospital for further evaluation and management. The patient, a known case of diabetes mellitus and hypertension, reported an insidious onset of right foot swelling over two months. A physical examination revealed stable vital signs; no significant abnormalities were observed during the systemic examination. Laboratory investigations indicated mild anemia and slightly elevated liver enzymes. Imaging studies, including MRI and CT scan, identified an ill-defined lesion on the medial aspect of the right foot, consistent with dermatofibroma. The patient underwent a below-knee amputation with inguinal lymph node dissection on 31st May 2024. The procedure, performed under spinal and epidural anesthesia, involved meticulous dissection and ligation, with the posterior flap sutured using Ethilon 2-0 (Ethicon, Cincinnati, OH, USA). Post-operative management included IV antibiotics and supportive care. The patient's postoperative course was uneventful, with a healthy suture line and stable vitals upon discharge. Histopathological evaluation of the resected specimen confirmed melanoma, with immunohistochemistry revealing HMB-45 and S-100 negativity. The patient was discharged with advice on local hygiene, physiotherapy, dietary recommendations, and a follow-up schedule. This case highlights the importance of comprehensive multidisciplinary management in treating malignancies complicated by chronic conditions. Early diagnosis, appropriate surgical intervention, and diligent post-operative care are crucial for favorable outcomes in complex oncological cases.

Survival prognostic analysis of laparoscopic D2 radical resection for locally advanced gastric cancer: A multicenter cohort study.

BACKGROUND: With the development of minimally invasive surgical techniques, the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer (GC) has gradually increased. However, the effect of this procedure on survival and prognosis remains controversial. This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence, guide clinical decision-making, optimize treatment strategies, and improve the survival rate and quality of life of patients. AIM: To investigate the survival prognosis and influencing factors of laparoscopic D2 radical resection for locally advanced GC patients. METHODS: A retrospective cohort study was performed. Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected. There were 442 males and 210 females. The mean age was 57 ± 12 years. All patients underwent a laparoscopic D2 radical operation for distal GC. The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence, metastasis, and survival. The follow-up period ended in December 2023. Normally distributed data are expressed as the mean ± SD, and normally distributed data are expressed as M (Q1, Q3) or M (range). Statistical data are expressed as absolute numbers or percentages; the χ 2 test was used for comparisons between groups, and the Mann-Whitney U nonparametric test was used for comparisons of rank data. The life table method was used to calculate the survival rate, the Kaplan-Meier method was used to construct survival curves, the log rank test was used for survival analysis, and the Cox risk regression model was used for univariate and multifactor analysis. RESULTS: The median overall survival (OS) time for the 652 patients was 81 months, with a 10-year OS rate of 46.1%. Patients with TNM stages II and III had 10-year OS rates of 59.6% and 37.5%, respectively, which were significantly different (P < 0.05). Univariate analysis indicated that factors such as age, maximum tumor diameter, tumor differentiation grade (low to undifferentiated), pathological TNM stage, pathological T stage, pathological N stage (N2, N3), and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer [hazard ratio (HR): 1.45, 1.64, 1.45, 1.64, 1.37, 2.05, 1.30, 1.68, 3.08, and 0.56 with confidence intervals (CIs) of 1.15-1.84, 1.32-2.03, 1.05-1.77, 1.62-2.59, 1.05-1.61, 1.17-2.42, 2.15-4.41, and 0.44-0.70, respectively; P < 0.05]. Multifactor analysis revealed that a tumor diameter greater than 4 cm, low tumor differentiation, and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients (HR: 1.48, 1.44, 1.81 with a 95%CI: 1.19-1.84). Additionally, postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate (HR: 0.57, 95%CI: 0.45-0.73; P < 0.05). CONCLUSION: A maximum tumor diameter exceeding 4 cm, low tumor differentiation, and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC. Conversely, postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.

Clinical and prognostic significance of follicular helper and regulatory T cells in bladder cancer draining lymph nodes.

Follicular helper and regulatory T cells (Tfh/TFR) cells are distinct subsets of CD4+ cells that have been recognized for their critical role in regulating cellular reactions within the germinal centers of lymphoid follicles. In the present study, we aimed to determine the presence and the frequency of these cells in draining lymph nodes of patients with bladder cancer (BC). Forty-six patients with BC who had undergone radical cystectomy and pelvic lymph node dissection were enrolled. Following routine pathological examination, a portion of the dissected lymph nodes was minced to obtain a single-cell suspension. Mononuclear cells were then separated using Ficoll-Hypaque gradient centrifugation, and the samples with proper viability (> 95%) were subjected to further analysis. To phenotype the follicular subsets, cells were stained with appropriate fluorochrome-conjugated antibodies specific for CD4, CXCR5, BCL6, and FOXP3. The cells were then acquired on a four-color flow cytometer. The data were analyzed with the FlowJo software version 10.8.1 package. Our analysis indicated that, on average 37.89 ± 16.36% of CD4+ lymphocytes in draining lymph nodes of patients with BC expressed CXCR5. The majority of them were negative for FOXP3, representing helper subsets (28.73 ± 13.66). A small percent simultaneously expressed BCL6 transcription factor (1.65% ± 1.35), designated as Tfh (CD4+BCL6+CXCR5+FOXP3-). While less than 10% of CD4+ lymphocytes expressed CXCR5 and FOXP3, 1.78 ± 2.54 were also positive for BCL6, known as TFR. Statistical analysis revealed that the frequency of both Tfh and TFR cells was higher in draining lymph nodes of patients with tumor-infiltrated nodes (P = 0.035 and P = 0.079, respectively) compared to those with negative ones. The percentage of these cells was also higher in high-grade tumors compared to low-grade ones (P = 0.031 for both). Our data collectively indicated that however approximately one third of CD4+ lymphocytes expressed CXCR5 and accordingly had the capacity to enter the follicles, less than 2% of them represented Tfh and TFR phenotypes. The percentage of these cells increased in progressed tumors and showed an association with negative prognostic factors.

Enhancing lymph node metastasis prediction in adenocarcinoma of the esophagogastric junction: A study combining radiomic with clinical features.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEJ) is increasing, and with poor prognosis. Lymph node status (LNs) is particularly important for planning treatment and evaluating the prognosis of patients with AEJ. However, the use of radiomic based on enhanced computed tomography (CT) to predict the preoperative lymph node metastasis (PLNM) status of the AEJ has yet to be reported. PURPOSE: We sought to investigate the value of radiomic features based on enhanced CT in the accurate prediction of PLNM in patients with AEJ. METHODS: Clinical features and enhanced CT data of 235 patients with AEJ from October 2017 to May 2023 were retrospectively analyzed. The data were randomly assigned to the training cohort (n = 164) or the external testing cohort (n = 71) at a ratio of 7:3. A CT-report model, clinical model, radiomic model, and radiomic-clinical combined model were developed to predict PLNM in patients with AEJ. Univariate and multivariate logistic regression were used to screen for independent clinical risk factors. Least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomic features. Finally, a nomogram for the preoperative prediction of PLNM in AEJ was constructed by combining Radiomics-score and clinical risk factors. The models were evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analyses. RESULTS: A total of 181 patients (181/235, 77.02%) had LNM. In the testing cohort, the AUC of the radiomic-clinical model was 0.863 [95% confidence interval (CI) = 0.738-0.957], and the radiomic model (0.816; 95% CI = 0.681-0.929), clinical model (0.792; 95% CI = 0.677-0.888), and CT-report model (0.755; 95% CI = 0.647-0.840). CONCLUSION: The radiomic-clinical model is a feasible method for predicting PLNM in patients with AEJ, helping to guide clinical decision-making and personalized treatment planning.

Breast cancer-related lymphedema: A critical review on recent progress.

Lymphedema is a chronic and debilitating condition characterized by an abnormal buildup of protein-rich fluid in the interstitial tissue, leading to the development of edema and tissue structural alterations. Breast cancer-related lymphedema (BCRL) remains a significant healthcare burden because it can develop within days and up to 11-years after the surgery. Specifically, axillary lymph node dissection leads to 30-50 % upper limb lymphedema, which involves the accumulation of protein-rich fluid. In this article, we provide a comprehensive/critical overview of post-mastectomy lymphedema, focusing on key aspects as diagnosis, prevention, and treatment methods. Beginning with clinical condition, the article explores the pathophysiology and risk factors associated with post-mastectomy lymphedema. It further delves into various diagnostic modalities available, highlighting the importance of early detection for optimal management of BCRL. We also examine preventive strategies, emphasizing the role of patient education, lifestyle modifications, and proactive measures in reducing the risk of lymphedema development. In terms of treatment, the article covers a wide array of interventions ranging from conservative approaches like manual lymphatic drainage and compression therapy to surgical techniques such as lymph node transfer and lymphaticovenular anastomosis. Thus, through a comprehensive synthesis of current evidence and clinical practices updates, the review aims to guide healthcare professionals in delivering preventive and effective care while improving outcomes for individuals affected by post-mastectomy lymphedema.

Fallopian tube cancer with inguinal lymph node metastasis as the first symptom: A case study and review of the literature.

INTRODUCTION AND IMPORTANCE: Fallopian tube cancer that is characterized only by inguinal lymph node metastasis without intra-abdominal widespread is rare. Here we report a patient with primary Fallopian tube cancer with bilateral inguinal metastases as the first symptom. CASE PRESENTATION: A 68-year-old patient with primary Fallopian tube cancer, with painless bilateral inguinal enlargement (7 × 6 cm on the right side, 3 × 2 cm on the left side) as the only manifestation, was confirmed by preoperative biopsy as metastatic high-grade serous denocarcinoma, consider the adnexal or peritoneal source. Pelvic MRI, abdominal CT and PET-CT showed irregular signal foci can be seen in the right adnexal area, with a maximum cross-section of about 7.5 × 7.0 × 4.0 cm, considering malignancy, ovarian cancer may be possible; bilateral pelvic wall, bilateral inguinal, right iliac vessels with hypermetabolic lymph nodes. Serum CA125 level was markedly elevated at 922.40 U/ml and HE4 at 394.50 pmol/L. No abnormality was found in gastrointestinal endoscopy. At exploratory laparotomy, the tumor was confined to the right rear of the uterus, and a solid tumor with a size of about 10 × 6 × 6 cm was seen. The surface was smooth and closely related to the uterus. There was almost no tumor spread in the pelvic abdominal cavity, but there was 50 ml of pale blood-colored peritoneal fluid. The right ovarian capsule was intact. Cytoreductive surgery was performed, postoperative pathology confirmed adenocarcinoma of the right fallopian tube, and the patient received six cycles of paclitaxel plus cisplatin combination chemotherapy were administered, with three 3-weeks intervals between cycles. And subsequent the patient participated in a clinical trial. The work has been reported in line with the SCARE criteria. CLINICAL DISCUSSION: Literature review indicates that inguinal lymph node as the first manifestation of fallopian tube cancer is not usual, and with no widespread lymphadenopathies and abdominopelvic cavity are even rarer. This case shows that rare cases with only inguinal lymph node metastasis may occur through the underlying lymphatic and/or hematogenous routes. CONCLUSION: The diagnosis of tubal cancer is sometimes complicated and delayed. For elderly women without nonspecific symptoms, especially those with obvious masses, detailed examinations, and imaging studies should be carried out in time. The treatment of tubal cancer is multi-modal. Due to the high risk of recurrence of fallopian tube cancer, the possibility of metastasis after the initial diagnosis is large, so it is very important to receive close and regular follow-up for patients with fallopian tube cancer after treatment. We suggest that more tumor centers study the possible mechanisms, metastasis patterns, biological characteristics, etc. of such patients, and at the same time efforts should be made to early differential diagnosis, and ultimately prolong the survival time of such patients.

Lymphatic system regulation of anti-cancer immunity and metastasis.

Cancer dissemination to lymph nodes (LN) is associated with a worse prognosis, increased incidence of distant metastases and reduced response to therapy. The LN microenvironment puts selective pressure on cancer cells, creating cells that can survive in LN as well as providing survival advantages for distant metastatic spread. Additionally, the presence of cancer cells leads to an immunosuppressive LN microenvironment, favoring the evasion of anti-cancer immune surveillance. However, recent studies have also characterized previously unrecognized roles for tumor-draining lymph nodes (TDLNs) in cancer immunotherapy response, including acting as a reservoir for pre-exhausted CD8+ T cells and stem-like CD8+ T cells. In this review, we will discuss the spread of cancer cells through the lymphatic system, the roles of TDLNs in metastasis and anti-cancer immune responses, and the therapeutic opportunities and challenges in targeting LN metastasis.

Prediction of lateral neck metastasis in patients with papillary thyroid cancer with suspicious lateral lymph ultrasonic imaging based on central lymph node metastasis features.

Neck lymphatic metastasis is a common occurrence with thyroid cancers, and pre operative lateral lymph node metastasis (LLNM) and postoperative lateral lymph node recurrence (LLNR) are two independent risk factors that are negatively associated with the prognosis of patients with thyroid cancer. The aim of the present study was to investigate the relationship between central lymph node metastasis (CLNM) and LLNM in patients with papillary thyroid carcinoma (PTC) with sonographically suspected LLNM, such as those without lymph node fine-needle aspiration (FNA) cytological results or negative FNA results at the time of diagnosis. The predictive ability of CLNM regarding LLNR was also investigated. The present study retrospectively reviewed the clinical data of 1,061 patients that were surgically treated for PTC and 128 patients with sonographically suspected lateral lymph nodes that received central lymph node dissection and lateral lymph node dissection at the Thyroid Department of The First Affiliated Hospital of Anhui Medical University (Hefei, China) from June 2019 to June 2021. In patients with suspicious ultrasonic images suggesting LLNM, a significant association between the central lymph node ratio (CLNR), the number of positive central lymph nodes and LLNM was demonstrated. Otherwise, there were no statistically significant differences between the CLNR in patients with PTC and patients with PTC without evidence of lateral cervical metastasis. However, the rate of LLNR increased significantly when the number of positive central lymph nodes was >3. In conclusion, the CLNR and the number of positive central lymph nodes could be used to predict LLNM in patients with PTC with sonographically suspect lateral lymph nodes, including those with no FNA cytological results or negative FNA results, which may potentially support physicians in making personalized clinical decisions.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer.

PURPOSE: In post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). METHODS: LPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. RESULTS: Among 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. CONCLUSIONS: LPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.

Current and Future Implications of Lymphedema Surgery in Head and Neck Reconstruction.

In this study, the authors shed light on the underappreciated realm of head and neck lymphedema (HNL) amid the backdrop of significant advancements in extremity lymphedema management. Despite its prevalence and impact, HNL has long been overlooked, attributed to its subtle symptom presentation and lack of awareness among primary care providers. The study delves into the unique challenges associated with diagnosing and treating HNL, emphasizing the predominance of internal swelling over external manifestations. The authors advocate for the refinement and standardization of outcome measures and the integration of innovative techniques such as indocyanine green lymphography and patient-reported outcomes.

Risk and Protective Factors of Postoperative and Persistent Hypoparathyroidism after Total Thyroidectomy in a Series of 1965 Patients.

BACKGROUND: Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy. Several risk factors have been identified, but data on postoperative follow-up are scarce. METHODS: The study focused on 1965 patients undergoing surgery for benign and malignant thyroid diseases at a tertiary-level academic center. Anamnestic, biochemical, surgical, pathological, and follow-up data were evaluated. HypoPTH was defined by a serum concentration of PTH < 10 pg/mL on the first or the second post-operative day. Persistent HypoPTH was defined by the need for calcium/active vitamin D treatment > 12 months after surgery. RESULTS: Postoperative HypoPTH occurred in 542 patients. Multivariate analysis identified the association of central lymph-nodal dissection, reduced preoperative PTH levels, a lower rate of parathyroid glands preserved in situ, and longer duration of surgery as independent risk factors. At a median follow-up of 47 months, HypoPTH regressed in 443 patients (more than 6 months after surgery in 7%) and persisted in 53 patients. Patients receiving a lower dose of calcium/active vitamin D treatment at discharge (HR 0.559; p < 0.001) or undergoing prolonged, tailored, and direct follow-up by the operating endocrine surgeon team had a significantly lower risk of persistent HypoPTH (2.4% compared to 32.8% for other specialists) (HR 2.563; p < 0.001). CONCLUSIONS: Various patient, disease, and surgeon-related risk factors may predict postoperative HypoPTH. Lower postoperative calcium/active vitamin D treatment and prolonged, tailored follow-up directly performed by operating endocrine surgeons may significantly reduce the rate of persistent HypoPTH.

Two Different Immune Profiles Are Identified in Sentinel Lymph Nodes of Early-Stage Breast Cancer.

In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs. The expression of an immune gene panel was analysed in SLNs from 32 patients with Luminal A early-stage BC (cT1-T2 N0). Using an unsupervised approach based on these expression values, this study identified two clusters, regardless of the SLN invasion: one evidencing an adaptive anti-tumoral immune response, characterised by an increase in naive B cells, follicular T helper cells, and activated NK cells; and another with a more undifferentiated response, with an increase in the activated-to-resting dendritic cells (DCs) ratio. Through a protein-protein interaction (PPI) network, we identified seven immunoregulatory hub genes: CD80, CD40, TNF, FCGR3A, CD163, FCGR3B, and CCR2. This study shows that, in Luminal A early-stage BC, SLNs gene expression studies enable the identification of distinct immune profiles that may influence prognosis stratification and highlight key genes that could serve as potential targets for immunotherapy.

Perioperative Predictive Factors for Tumor Regression and Survival in Non-Small Cell Lung Cancer Patients Undergoing Neoadjuvant Treatment and Lung Resection.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into a lung adenocarcinoma group (LUAD) and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small-cell lung cancer were included in the study. A total of 58 (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Additionally, 9 (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III, respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7 cm), and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR [95% confidence interval, p-value] of 6.88 [2.40-19.77, p < 0.0001], 3.13 [1.11-8.83, p = 0.0310], and 3.76 [1.20-11.81, p = 0.0233], respectively). Age > 70 years, extended resection > one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

SENECA study: staging endometrial cancer based on molecular classification.

OBJECTIVE: Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. METHODS: The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. RESULTS: Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). CONCLUSIONS: Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.

Transcriptional expression of SLC16A7 as a biomarker of occult lymph node metastases in patients with head and neck squamous cell carcinoma.

PURPOSE: Glucose is the main energy substrate of tumor cells. This study aims to assess whether the transcriptional expression of glucose metabolism-related genes is associated with occult lymph node metastases in head and neck squamous cell carcinoma (HNSCC) patients. METHODS: We examined the transcriptional expression of a panel of glucose metabolism-related genes in a cohort of 53 patients with HNSCC without cervical lymph node involvement at the time of diagnosis (cN0) and subsequently treated with elective neck dissection. RESULTS: Occult lymph node metastases were found in 37.7% (n = 20) of the patients. Among the analyzed genes, SLC16A7 exhibited the strongest association with the presence of occult lymph node metastases. Patients with occult lymph node metastases (cN0/pN +) had significantly lower SLC16A7 expression values (p = 0.001). Patients with low SLC16A7 expression (n = 17, 32.1%) had a frequency of occult lymph node metastases of 76.5%, while for patients with high SLCA16A7 expression (n = 36, 67.9%) it was 19.4% (P = 0.0001). A multivariable analysis showed that patients with low expression of SLC16A7 had a 12.6 times higher risk of developing occult lymph node metastases. CONCLUSION: cN0 HNSCC patients with low SLC16A7 expression had a higher risk of occult lymph node metastases.

The transcription regulator ID3 maintains tumor-specific memory CD8+ T cells in draining lymph nodes during tumorigenesis.

During tumorigenesis, the recently identified tumor-specific memory T cells in draining lymph nodes (TdLN-TTSM cells) play a pivotal role in tumor repression that gives rise to progenitor exhausted T (TPEX) cells and further replenishes tumor-specific CD8+ T cells residing in the tumor microenvironment (TME). However, how TTSM cells are maintained in TdLN is largely unknown. Here, we show that the transcription regulator ID3 (inhibitor of DNA binding 3) is highly expressed by TTSM cells compared with other CD8+ T cell subsets. The deficiency of ID3 significantly interrupts the maintenance of TTSM and TPEX cells, resulting in decreased tumor-infiltrating CD8+ T cells and impaired tumor control. Consistent with this, overexpression of ID3 in CD8+ T cells increases the TTSM cell population and enhances the anti-tumor immune response.