Regional Nodes Research Articles

Clinical Significance of HHLA2 as a Novel Therapeutic Target for Colorectal Cancer.

Colorectal cancer (CRC) is a high-indence malignance of the digestive system with a high mortality rate in the world. The results are desired to provide an important theoretical basis for discovering new therapeutic targets for CRC. The expression of human endogenous retrovirus-H-long terminal repeat association protein 2 (HHLA2) in human CRC was detected to explore its correlationship with clinicopathological features and prognosis of patients and its potential in treating CRC. Western blot was employed to detect HHLA2 expression in fresh tissues obtained from 6 CRC patients' excisions, including cancer, paracancer, and normal issues. Immunohistochemical staining was employed to determine HHLA2 expression in paraffin-embedded specimens of 139 patients with colorectal cancer, and its relationship with the clinicopathological profiles and survival was analyzed. Small interfering RNA (siRNA) targeting HHLA2 was used to transfect CRC cells to silent HHLA2. MTT, plate colony formation, cell scratch, and Transwell assay were conducted to observe the proliferation, migration, and invasion of CRC cells. HHLA2 protein was expressed in human colorectal cancer tissues, paracancer tissues and normal tissues, which was significantly upregulated in cancer tissues (P<0.01). HHLA2 expression level in CRC tissues showed a close correlationship with the invasion depth of the tumor (P=0.000), metastasis of regional lymph nodes (P=0.018), clinical stage (P=0.010), and patient survival (P=0.011). Correlation with gender (P=0.873), age (P=0.864), location of the tumor (P=0.768), degree of tumor differentiation (P=0.569) and distant metastasis (P=0.494) exhibited no significance. The survival time of CRC patients with high and low HHLA2 expression groups was 43.231 months and 55.649 months, respectively, with a statistical difference between the two groups (P=0.001). Silencing HHLA2 inhibited proliferation, migration and invasion of CRC cells significantly. HHLA2 is overexpressed in CRC tissues which is associated with poor prognosis of patients. HHLA2 might be recognized as a new candidate for adjuvant diagnosis and prognosis of CRC, as well as a promised new target for immunotherapy of CRC.

Wire injury induced moderate aortic valve stenosis in mice is accompanied by a chronic systemic inflammatory reaction

Abstract Background Patients with aortic valve stenosis (AS) have elevated serum levels of inflammation markers, and blood cytokine levels correlate with ventricular recovery after transcatheter aortic valve replacement. While presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon AS has been performed, yet. Purpose Hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods AS was induced by wire injury (WI) or sham surgery was performed in 3-4 months old male C57Bl/6J mice. AS severity, left ventricular (LV) function and hypertrophy indices were assessed with echocardiography (echo). After four weeks, explanted organs were weighted, and flow cytometry identified total leukocyte numbers in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes) and uptake of Cy5-labelled perfluorocarbon nanoemulsions by whole blood leukocytes. Costimulatory molecules (flow cytometry, RT-qPCR) and cytokines (RT-qPCR, Multiplex Immunoassay) were analysed in heart, peripheral immune organs and blood. Results R-values were positive for spleen weight correlation with AS severity, cardiac function and mass suggesting cardiac hypertrophy to preserve heart function. Myocardial myeloid and T cell r-values were positive or negative, respectively, for correlation with spleen and liver weight, hinting at T cell recruitment from peripheral stores. Immune cell numbers in peripheral lymph nodes and spleen showed negative r-values for correlation with heart hypertrophy indices; number of liver myeloid cells correlated negatively with LV wall thickness (monocytes=-0.8571, p=0.0238) suggesting immune cell recruitment to hypertrophic hearts. Cytokine mRNA levels trended mainly towards increase in heart and regional lymph nodes and reduction in spleen and liver after WI. Correlation with echo was more homogeneous after WI, with r-values mainly positive, except of T cell activation markers, for aortic valves, but negative for myocardium, hinting at mechanisms preserving heart function. Correlating unchanged cytokine protein levels in myocardium and plasma with echo, r-values were mostly positive for myocardium, and were more positive than in sham for plasma. Echo and costimulatory molecule correlation showed a more homogeneous pattern in WI, with mostly positive r-values in myocardium and periphery, while most r-values were negative in sham. Together with reduced PFC-uptake by lymphatic cells, this hints at systemic immune cell activation in AS. Conclusion The results suggest that number and activation state of leukocytes in peripheral organs are directly linked to cardiac processes in AS. Considering the pathological value of inflammation, it is crucial to in future studies find out if modulation of the systemic inflammatory reaction relieves severity of AS and prevents development of heart failure.

Selective Sentinel Node Dissection in Melanoma with Trends and Future Directions

Starting with its earliest descriptions, melanoma has been recognized as a tumor with a predilection for metastasis to regional lymph nodes. This tendency led to initial recommendations for very aggressive early surgical management of the regional nodal basin. However, those recommendations were the source of much controversy over nearly a century, until the minimally invasive surgical technique of sentinel lymph node (SLN) biopsy was developed by Morton, Cochran and colleagues. This technique has been evaluated in a series of prospective clinical trials, which have clarified its role and the management of lymph nodes in this disease. Current controversies relating to SLN biopsy include optimal selection of patients for the procedure, the role of gene expression profiling in initial melanoma management, and the potential therapeutic effects of SLN biopsy-based management. In addition, the SLN appears to be a rich source of data relating to the host–tumor interface and the immune microenvironment, which may advance our understanding of the biology of melanoma. Finally, although the surgical technique is well developed at this point, there may be additional technical improvements that are possible as well.

Response of lymphoid organs to immunization with Fc fragments of IgG carrying epitopes specific to regulatory rheumatoid factor

Previously, we identified a new factor of autoimmunity downregulation, called regulatory rheumatoid factor (regRF). The production of regRF was associated with the resistance of animals to the experimental autoimmune diseases or with the remission in animals that are sensitive to the autoimmune diseases. The action of regulatory rheumatoid factor is based on the killing of activated CD4 T lymphocytes expressing PD-1, which makes it possible to restrain the expansion of lymphocytes, including autoreactive ones. RegRF-specific epitopes (regRF epitopes) can be induced on IgG Fc fragments. Immunization of rats with homologous IgG Fc fragments bearing regRF epitopes suppresses symptoms, lymphocytic infiltration and target tissue damage in several experimental models of autoimmune diseases. An in vitro study of the mechanisms of regRF-producing lymphocytes activation by IgG Fc fragments carrying regRF epitopes showed that IgG Fc fragments carrying regRF epitopes are T cell-independent antigens type 2. The reactions of the immune system, in particular in lymphoid organs, to T cell-independent antigens type 2, especially having a protein nature, are poorly studied. The purpose of this work is to study the reactions of the spleen and lymph nodes of rats to immunization with IgG Fc fragments carrying regRF epitopes. Wistar rats were immunized subcutaneously with 500 μg of homologous IgG Fc fragments carrying regRF epitopes. Control animals received an injection of phosphate-buffered saline. Immunization with IgG Fc fragments carrying regRF epitopes caused a transient increase of regulatory rheumatoid factor blood level with a maximum on day 7 after immunization. It was found that immunization with IgG Fc fragments carrying regRF epitopes does not cause a reaction in the regional and distal lymph nodes of rats, but induces the development of secondary follicles in spleen that exist for at least 28 days. On day 49, the number of follicles with germinal centers in the spleen of rats immunized with IgG Fc fragments carrying regRF epitopes was lower than in control rats. Consequently, the reaction of splenic follicles in rats immunized with IgG Fc fragments carrying regRF epitopes is transient. No changes were detected in the periarteriolar lymphoid sheaths (splenic T cell zone) in rats immunized with IgG Fc fragments carrying regRF epitopes. Thus, IgG Fc fragments carrying regRF epitopes, being a T cell-independent antigens type 2, do not cause a reaction in the lymph nodes, but induce the development of germinal centers in the spleen that exist for several weeks.

A case of successful conversion surgery for unresectable gallbladder cancer treated with durvalumab in combination with gemcitabine plus cisplatin.

We report a rare case of a patient with initially unresectable gallbladder cancer who underwent conversion surgery with durvalumab in combination with gemcitabine plus cisplatin and achieved an R0 resection. A 68year-old woman was found to have gallbladder cancer and multiple enlarged lymph nodes around the suprapancreatic rim and hepatic hilum invading the proper hepatic artery on computed tomography. The diagnosis was cT3cN2cM0, cStage IVB. After eight cycles of durvalumab in combination with gemcitabine plus cisplatin, all tumor markers became negative, and lymph node invasion of the hepatic artery disappeared. The patient underwent conversion surgery with gallbladder bed resection and regional lymph node dissection. There was no need for hepatic artery reconstruction. Pathology revealed ypT2aypN0ycM0, ypStage IIA, and radical resection was considered. Immunostaining of tissue collected at the time of endoscopic ultrasound-guided tissue acquisition revealed less than 1% programmed death ligand-1 expression. The patient continued adjuvant chemotherapy with single-agent durvalumab every 4weeks and maintained a relapse-free survival of 8months postoperatively. The utility of durvalumab in combination with gemcitabine plus cisplatin in unresectable gallbladder cancer independent of programmed death ligand-1 expression has been confirmed and may be an important option in future multimodal treatment, including conversion surgery.

Diagnostic Accuracy of Computed Tomography and Clinical Examination in the Assessment of Mandibular Invasion of Oral Squamous Cell Carcinomas

Introduction: Computed tomography (CT) scan precisely shows soft and hard tissues in the same test hereby determines the lesion extension, involvement of regional node as well as of bone. Current study was aimed to evaluate the efficacy of clinical examination and CT to assess mandibular invasion in oral squamous cell carcinoma. Materials and methods: This cross-sectional study was conducted at Dhaka Dental College Hospital from July, 2016 to July, 2017 among conveniently selected 35 patients of histologically confirmed squamous cell carcinoma which was close to the mandible. The patients underwent proper clinical examination. CT scan was performed; preoperative staging and treatment plan was formulated according to the status of bone invasion. After mandibulectomy, the resected specimens were sent for histopathology. The findings from clinical examination and CT were then correlated with the gold standard, postoperative histopathology. Results: Clinical examination accurately detected 22 cases to have bone invasion and 8 cases with no bone invasion. It also gave 2 false positive and 3 false negative results. On the other hand CT accurately detected 24 cases to have bone invasion and 9 cases with no bone invasion. It provided one false positive and one false negative result. However, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of clinical examination were 88%, 80%, 91.67%, 72.73%, 85.71% respectively (p = 0.0002) and of CT were 96%, 90%, 96%, 90%, 94.28% respectively (p &lt; 0.0001). Clinical examination and CT were found sensitive enough and have an acceptable range of specificity as primary investigative modalities. CT scan outperforms clinical examination in terms of sensitivity, specificity, NPV, and accuracy. Conclusion: CT scan imaging is the method of choice for planning treatment in advanced oral squamous cell carcinoma. This study reveals how a CT scan can provide additional diagnostic value to detect bone invasion. Update Dent. Coll. j: 2024; 14(2): 21-26

Exploring Spatiotemporal Interaction Patterns of Dockless Shared Bicycle Networks: A Case Study of Shenzhen, China

Abstract. The explosive development of shared bicycles has changed the way people travel. In parallel with the urbanization process, shared bicycles have emerged as a significant mode of transportation, especially for the first and last mile transit. With the aim of obtaining a comprehensive understanding of the spatiotemporal patterns underlying shared bicycle usage, this study takes Shenzhen, China as a case study. Drawing on the principles and techniques of complex network analysis, the research adopts a spatial grid framework, treating each grid as a node, the flow of shared bicycles as an edge, and the flow frequency as the corresponding weight. Subsequently, the spatiotemporal interaction networks of different periods of working days and weekends are constructed respectively, based on which the topological characteristics are analysed. The results show that the spatiotemporal interaction networks exhibit high regional connectivity and node interdependence, suggesting the presence of a small-world phenomenon.

Androgen deprivation therapy, neoadjuvant androgen deprivation therapy, and adjuvant androgen deprivation therapy in patients with locally advanced prostate cancer: a multi-center real-world retrospective study.

Determining the potential benefit of neoadjuvant androgen deprivation therapy (ADT) and adjuvant ADT in patients with locally advanced prostate cancer (LAPC) undergoing complete resection. 139 patients diagnosed with cT3-4, or cN+ LAPC in Xiangya Hospital and The First Affiliated Hospital of University of South China from 2010 to 2021 were collected. Cancer-specific survival (CSS) and overall survival (OS) of patients were assessed using Kaplan-Meier and Cox proportional risk analysis. We also analyzed the functional outcomes of two subgroups of patients who underwent radical prostatectomy (RP). Of the 182 patients with cT3-4, or cN+ LAPC, 139 patients (76.4%) were enrolled in the study with a 5-year survival rate of 82.3%. 45 patients (32.4%) received ADT alone, 46 patients (33.1%) received neoadjuvant ADT before surgery, and the remaining 48 patients (34.5%) received surgery with adjuvant ADT. Neoadjuvant ADT before surgery and surgery with adjuvant ADT were associated with significantly improved survival compared with ADT alone. Multivariate Cox models showed that neoadjuvant ADT before surgery (hazard ratio [HR], 0.29; 95% CI 0.13-0.92) or surgery with adjuvant ADT (HR, 0.26; 95% CI 0.16-0.78) was associated with improved CSS compared with ADT alone. Regional lymph node metastasis, positive lymphovascular invasion, and Gleason score 9 + were independent predictors of LAPC CSS and OS. More patients in the neoadjuvant ADT before surgery group achieved final continence status within 12 months after surgery (93.48% v 77.08%). CSS and OS were significantly prolonged in cT3-4, or cN+ LAPC patients who received neoadjuvant ADT before surgery and surgery with adjuvant ADT compared to ADT alone.

Exploring Molecular Signatures in Early-Stage Pancreatic Ductal Adenocarcinoma: Implications for Patient Management and Therapeutic Strategies

Abstract Introduction/Objective Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges to patient survival, predominantly due to its tendency for late-stage diagnosis and high rates of post-surgical cancer recurrence. Therefore, a comprehensive understanding of the molecular characteristics associated with the early stages of PDAC is imperative. This understanding holds the potential to improve patient treatment strategies by enabling targeted interventions and personalized therapies. Methods/Case Report Initially, RNA-seq datasets of early-stage PDAC cases (stages IA, IB, IIA, and IIB, all without distant metastasis; M0) were extracted from the GEO database. Subsequently, the datasets were analyzed in four distinct groups, and differentially expressed genes were identified within each group. Group 1 compared T1T2 cases with T3 cases (T: primary tumor), irrespective of N status (N: regional lymph nodes), while group 2 compared N0 cases with N1 cases, regardless of T status. Group 3 included comparisons between T1T2N0 cases and T3N0 cases, and group 4 compared T1T2N1 cases with T3N1 cases. Utilizing a Venn diagram, commonalities between gene expression profiles were isolated. Afterward, gene ontology and signaling pathways were determined using KEGG and Enrichr. Finally, a protein network was constructed, and the proteins were evaluated using the GEPIA and TCGA clinical databases. Results (if a Case Study enter NA) The study encompassed a total of 43 cases, with 25 (58.1%) being male and 18 (41.9%) female. The mean age of the participants was 64.4 years. In group 1, the expression levels of MUC5AC, AKAP13, and SPG7 were significantly upregulated in T3 cases. In group 2, STAB1, PDLIM1, and MTUS1 emerged as the top upregulated genes in N1 cases. Group 3 exhibited notable upregulation of CCNL2, CEACAM6, and TSPAN3 in T3N0 cases, while group 4 demonstrated marked upregulation of LTBR, AKAP12, and BOP1 in T3N1 cases. These genes exhibited diverse functions in PDAC progression. They contributed to the regulation of gene expression and cell cycle progression, modulating cell proliferation, inhibiting tumor growth, regulating cell signaling, and were involved in cytoskeletal organization. Conclusion The upregulated genes in cases with the T3 and/or N1 staging components may shed light on the potential mechanisms of progression from stage IA/B to stage IIA/B in PDAC cases. Furthermore, the identified genetic alterations may hold potential therapeutic and prognostic applications for future use in the early stages of PDAC.

Kimura Disease: An Atypical Presentation

Abstract Introduction/Objective Kimura disease is a benign, chronic inflammatory process which presents with enlarged, painless lymphadenopathy. The etiology is currently unknown. It is most commonly seen in young males of Asian descent and is rare in other populations. It typically affects the subcutaneous tissue and regional lymph nodes, as well as the orbit and adnexal tissues. Clinically, peripheral eosinophilia and increased levels of immunoglobulin are commonly seen. Histologically, the disease presents with follicular hyperplasia with germinal center formation, hyperplastic vasculature, increased eosinophilic inflammatory infiltrate, and characteristic Warthin-Finkedly cells. Methods/Case Report A 70-year-old white male with no significant past medical history presented to an outpatient clinic with a painless right eyebrow mass. The mass had grown in size which prompted the patient to seek evaluation. The decision to excise the mass was made. Upon pathologic review, hematological workup was performed, and the case was subsequently diagnosed as Kimura disease. Results (if a Case Study enter NA) The specimen was excised and H&amp;E showed background benign fibroadipose tissue with prominent, lymphoid follicles. Within the follicles, there was a significant increase in eosinophils. Warthin- Finkeldey cells were commonly identified within germinal centers as well. Immunohistochemical staining was performed with appropriate controls which ruled out other common lymphoid malignancies and to the diagnosis of Kimura Disease. Conclusion Kimura disease is a rare, benign inflammatory disorder that most commonly affects the lymph nodes. It may be overlooked histologically when the patient does not fit the typical clinical picture. It can closely resemble neoplastic, hematologic conditions, and it should be distinguished from a more aggressive entity due to its benign, indolent behavior. From a pathologist’s point of view, because it occurs almost exclusively in young, Asian males, it is important to consider when presented with an atypical demographic to avoid unnecessary additional workup.

SURGICAL TREATMENT OF RECTAL CANCER WITH PRESERVATION OF THE LEFT COLIC ARTERY AND ICG NAVIGATION

Goal. To analyze the peculiarities of surgical diagnosis of lymphogenic metastasis in patients with colorectal cancer. Generalization of data from Ukrainian and foreign literature, results of randomized studies and meta-analyses. The study is based on the results of observation of 88 patients with colorectal cancer (CRC) of the prospective study group. To analyze the features of surgical diagnostics of lymphogenic metastasis in patients with colorectal cancer. Materials and methods. The results of surgical treatment of 88 patients with rectal cancer were analyzed and systematized. These patients underwent examination and treatment in 2023-2024 at the "Prykarpattian Clinical Oncology Center of the Ivano-Frankivsk Regional Council." The study included patients with stage II-III colorectal cancer (T2-3N0-2M0) without complicated courses. All patients received treatment based on NCCN recommendations. Surgical treatment was performed in standard volume with the removal of all regional lymph node groups and preservation of the left colic artery using real-time lymph node mapping with indocyanine green. All patients were divided into two study groups: Group I included 45 patients who underwent anterior or low anterior resection of the rectum with preservation of the left colic artery. This group was subdivided into two subgroups: Ia – 13 patients who underwent intraoperative indocyanine green injection for real-time lymph node visualization. Ib – 32 patients who did not receive this drug but underwent the same volume of surgery. Group II consisted of 43 patients who underwent anterior or low anterior resection of the rectum with high ligation of the inferior mesenteric artery. This group served as the control group. Results. The main mechanisms of lymphogenic metastasis in colorectal cancer patients in Ivano-Frankivsk were characterized. Literature data on the features of surgical diagnostics of colorectal cancer metastasis were summarized. A review of literature shows the social significance of these studies, as this pathology often leads to patient disability, requiring surgical interventions and further palliative treatment due to the widespread metastasis associated with this disease. The priority task for researchers remains the search for the most effective treatment methods for this pathology, based on randomized studies of colorectal cancer treatment and international protocols. According to the literature, surgical treatment of colorectal cancer remains insufficiently effective at the current stage of oncology. Modern methods offer low 5-year survival rates, emphasizing the need to study factors for individualized treatment. The overall 5-year survival rate for colorectal cancer patients from 2018-2022 was (45.8±2.3)%. The effectiveness of using real-time ICG navigation for lymph node mapping and preservation of the left colic artery in stage II-III (T2-4N1-2M0) rectal cancer patients has been proven. This technique allows for optimal lymphadenectomy, reducing the frequency of surgical complications by 14.7% (p&lt;0.05). Conclusion. Ensuring radical resection of rectal cancer while maximizing blood supply preservation to the anastomosis is the main goal of colorectal surgeons. Over the past two decades, surgical techniques have significantly improved due to advancements in surgical equipment. It is anticipated that surgical technologies will further evolve towards enhancement and individualization in the future. Our procedure serves as an example of modern and personalized rectal cancer surgery.

Node Reporting and Data System Combined With Computed Tomography Radiomics Can Improve the Prediction of Nonenlarged Lymph Node Metastasis in Gastric Cancer.

To investigate the diagnostic performance of Node Reporting and Data System (Node-RADS) combined with computed tomography (CT) radiomics for assessing nonenlargement regional lymph nodes in gastric cancer (GC). Preoperative CT images were retrospectively collected from 376 pathologically confirmed of gastric adenocarcinoma from January 2019 to December 2023, with 605 lymph nodes included for analysis. They were divided into training (n = 362) and validation (n = 243) sets. Radiomics features were extracted from venous-phase, and the radiomics score was obtained. Clinical information, CT parameters, and Node-RADS classification were collected. A combined model was built using machine-learning approach and tested in validation set using receiver operating characteristic curve analysis. Further validation was conducted in different subgroups of lymph node short-axis diameter (SD) range. Node-RADS score, SD, maximum diameter of thickness of tumor, and radiomics were identified as the most predictive factors. The results demonstrated that the integrated model combining SD, maximum diameter of thickness of tumor, Node-RADS, and radiomics outperformed the model excluding radiomics, yielding an area under the receiver operating characteristic curve of 0.82 compared with 0.79, with a statistically significant difference (P < 0.001). Subgroup analysis based on different SDs of lymph nodes also revealed enhanced diagnostic accuracy when incorporating the radiomics score for the 4- to 7.9-mm subgroups, all P < 0.05. However, for the 8- to 9.9-mm subgroup, the combination of the radiomics did not significantly improve the prediction, with an area under the receiver operating characteristic curve of 0.85 versus 0.85, P = 0.877. The integration of radiomics scores with Node-RADS assessments significantly enhances the accuracy of lymph node metastasis evaluation for GC. This combined model is particularly effective for lymph nodes with smaller standard deviations, yielding a marked improvement in diagnostic precision. The findings of this study indicate that a composite model, which incorporates Node-RADS, radiomics features, and conventional parameters, may serve as an effective method for the assessment of nonenlarged lymph nodes in GC.

Node-sparing modified short-course Radiotherapy Combined with CAPOX and Tislelizumab for locally Advanced MSS of Middle and low rectal Cancer (mRCAT): an open-label, single-arm, prospective, multicentre clinical trial

BackgroundNeoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC.MethodsThis was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed.DiscussionIn our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer.Trial registrationThis study was registered at www.clinicaltrials.gov. Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Construction and validation of a nomogram model for lymph node metastasis of stage II-III gastric cancer based on machine learning algorithms.

Gastric cancer, a pervasive malignancy globally, often presents with regional lymph node metastasis (LNM), profoundly impacting prognosis and treatment options. Existing clinical methods for determining the presence of LNM are not precise enough, necessitating the development of an accurate risk prediction model. Our primary objective was to employ machine learning algorithms to identify risk factors for LNM and establish a precise prediction model for stage II-III gastric cancer. A study was conducted at Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between May 2010 and December 2022. This retrospective study analyzed 1147 surgeries for gastric cancer and explored the clinicopathological differences between LNM and non-LNM cohorts. Utilizing univariate logistic regression and two machine learning methodologies-Least absolute shrinkage and selection operator (LASSO) and random forest (RF)-we identified vascular invasion, maximum tumor diameter, percentage of monocytes, hematocrit (HCT), and lymphocyte-monocyte ratio (LMR) as salient factors and consolidated them into a nomogram model. The area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curves were used to evaluate the test efficacy of the nomogram. Shapley Additive Explanation (SHAP) values were utilized to illustrate the predictive impact of each feature on the model's output. Significant differences in tumor characteristics were discerned between LNM and non-LNM cohorts through appropriate statistical methods. A nomogram, incorporating vascular invasion, maximum tumor diameter, percentage of monocytes, HCT, and LMR, was developed and exhibited satisfactory predictive capabilities with an AUC of 0.787 (95% CI: 0.749-0.824) in the training set and 0.753 (95% CI: 0.694-0.812) in the validation set. Calibration curves and decision curves affirmed the nomogram's predictive accuracy. In conclusion, leveraging machine learning algorithms, we devised a nomogram for precise LNM risk prognostication in stage II-III gastric cancer, offering a valuable tool for tailored risk assessment in clinical decision-making.

HER2 amplification and PD-L1 expression in invasive stratified mucin-producing carcinoma of the cervix: a clinicopathological analysis of eighteen cases

Objective: To investigate the clinicopathological features, prognosis and the expression of HER2 and PD-L1 in invasive stratified mucin-producing carcinoma of the cervix (ISMC). Methods: The clinicopathological data of 18 ISMC cases with radical resection of the cervix diagnosed in the Daping Hospital, Army Medical University from January 2018 to December 2023 were collected and retrospectively analyzed. PD-L1 and HER2 immunohistochemical staining and HER2 FISH were conducted. Results: The patient ages ranged from 31 to 72 years, with an average of 45 years. Approximately 8% of cervical adenocarcinoma cases in our hospital during the same period. Eleven cases were pure ISMC, and 7 cases were mixed-type ISMC, with the component of squamous cell carcinoma or usual-type adenocarcinoma. One case showed concurrent small cell neuroendocrine carcinoma (SCNEC). Three cases were diagnosed through biopsy (3/18). Five cases were of Silva pattern B and 13 cases of Silva pattern C. Three cases showed regional lymph node metastasis. Thirteen patients were disease-free at the end of the follow-up, while the ISMC patient with concurrent SCNEC developed distant metastasis. Fifteen cases (15/18) had PD-L1 expression with CPS≥1, and 7 cases (7/18) had PD-L1 TPS≥1%. One case of HER2 3+ and one case of HER2 2+ were both positive for FISH amplification; two cases HER2 1+, 14 cases HER2 0. Conclusions: Cervical ISMC is rare, has a wide spectrum of morphology, and can coexist with other types of cervical cancer. PD-L1 is positive in most of the ISMC cases, while HER2 is amplified or lowly expressed in a small portion of them. Thus, it is possible to treat ISMC patients with therapies targeting PD-L1 and therapy targeting HER2.

Patterns of failure with 18F-DCFPyL PSMA-PET/CT in the post-prostatectomy setting: A regional cohort analysis.

This study aimed to assess the detection rate of prostate cancer recurrence by prostate-specific member antigen positron emission tomography/computed tomography (PSMA PET/CT) with 18F-DCFPyL in patients with residual disease or biochemical recurrence (BCR), and its association with surgical pathology and prostate-specific antigen (PSA) kinetics. Men from South Central Ontario enrolled in the PSMA Registry for Recurrent Prostate cancer (PREP) between April 2019 and December 2021 after radical prostatectomy (RP) and who had 1) pathologic stage N1 or persistent elevated PSA; or 2) BCR (PSA >0.10 ng/mL) where initial postoperative PSA was undetectable were included. A total of 169 men (median age 68 years; interquartile range [IQR] 62-71) with complete data met the above criteria. The median PSA was 0.27 ng/mL (IQR 0.16-0.85) prior to PSMA-PET. Overall positivity rate 59%; when PSA was <0.40 ng/mL, overall positivity rate 42% vs. 85% with PSA ≥0.40 ng/mL (p<0.001). Higher pathologic tumor stage increased detection of regional lymph nodes (LN) (pT2-3a: 32% vs. pT3b: 69%, p<0.001) but not distant metastases (pT2-3a: 12% vs. pT3b: 24%, p=0.15). PSMA-PET detected 18% with prostate bed, 42% with regional LN disease, and 44% with pelvic-only disease. The three most involved LN chains were the internal (21%) and external (20%) iliac, and obturator chains (16%). This prospective study of patients with residual disease or BCR after RP illustrates patterns of failure that could impact diagnosis and postoperative management. Such patients have significant risk of regional LN positivity on PSMA-PET highlighting a need to include pelvic LN within salvage radiotherapy volumes.

Regularity and correlation analysis of regional lymph node metastasis in nonoperative patients with non-small cell lung cancer based on positron emission tomography/computed tomography images

BackgroundDefinitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced, inoperable non-small cell lung cancer (NSCLC). Previous studies have mainly focused on examining local failure and recurrence patterns after surgery and the principles of lymph node metastasis (LNM) in surgical candidates with NSCLC. However, these studies were just only able to guide postoperative radiotherapy (PORT) and the patterns of LNM in patients with resected NSCLC was inadequate to represent that in locally advanced inoperable NSCLC patients for guiding target volume delineation of CCRT. In this study, we aimed to analyze the metastasis regularities and establish the correlations between different lymph node levels in NSCLC patients without any intervention using positron emission tomography/computed tomography (PET/CT) images.MethodsOverall, 358 patients with N1–N3 NSCLC admitted in our hospital between 2018 and 2022 were retrospectively analyzed. The diagnosis of metastatic lymph nodes was reviewed and determined using the European Organization for Research and Treatment of Cancer standard and the standardized value of the PET/CT examination. Univariate and multivariate analysis were performed to investigate the correlations between the different levels were evaluated by using of the chi-square test and logistic regression model.ResultsThe lymph nodes with the highest metastasis rates in patients with left lung cancer were in order as follows: 10L, 4L, 5, 4R, and 7; while in those with right lung cancer they were 10R, 4R, 7, 2R, and 1R. Notably, we found left lung patients were more likely to have contralateral hilar, mediastinal and supraclavicular lymph nodes involved, and the right lung group exhibited a higher propensity for ipsilateral mediastinum and supraclavicular lymph node invasion. Furthermore, correlation analysis revealed there were significant correlative patterns in the LNM across different levels.ConclusionsThis study elucidated the patterns of primary LNM in patients with NSCLC who had not undergone surgery (without any treatment interventions) and the correlations between lymph node levels. These findings were expected to provide useful reference for target volume delineation in definitive concurrent chemoradiotherapy in locally advanced NSCLC patients.

Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial.

This multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival. The patients in the TKI plus TRT group received 60 Gy to primary lung tumor and positive regional lymph nodes. Radiotherapy for metastases to other sites was determined by clinicians. The primary end point was the progression-free survival (PFS). Secondary end points included overall survival (OS) and treatment-related adverse events (TRAEs). The first and second interim analyses were performed in March 2021 and March 2022. Between April 14, 2016, and February 25, 2022, a total of 118 patients were enrolled. Compared with the TKI alone group, the TKI plus TRT group achieved significantly better PFS (hazard ratio [HR], 0.57; P = .004) and OS (HR, 0.62; P = .029). The median PFS was 10.6 months in the TKI alone group and 17.1 months in the TKI plus TRT group. The median OS was 26.2 months and 34.4 months in the TKI alone group and TKI plus TRT group, respectively. The TKI plus TRT group showed better local control but was associated with a higher incidence of severe TRAEs (11.9% v 5.1%). For patients with EGFR-mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent TRT improves the PFS and OS, and TRAEs are acceptable and tolerable.

7235 Papillary Thyroid Carcinoma in a Hyperfunctioning Thyroid Nodule

Abstract Disclosure: J. Yang: None. P.V. Nadkarni: None. Background: The prevalence of malignancy in a hyperfunctioning or hot thyroid nodule is considered to be low. According to the 2015 American Thyroid Association Guidelines, no cytologic evaluation is routinely recommended for hyperfunctioning nodules since they are rarely associated with malignancy (1). We present a case of a 71-year-old female with a hot nodule containing papillary thyroid cancer. Clinical Case: A 71-year-old female with Type 1 diabetes mellitus and coronary artery disease on dual antiplatelet therapy was found to have a 1.5 cm firm, non-tender right-sided thyroid nodule on a routine physical exam. Laboratory tests demonstrated low TSH &amp;lt;0.01 (normal 0.36 - 3.74 m[IU]/L) and FT4 level elevated at 1.62 (normal 0.76 -1.46 ng/dL). She noticed palpitations and started on low dose Methimazole. Thyroid ultrasound results showed a 2.1 x 2.0 x 2.0 cm right inferior lobe thyroid nodule. This thyroid nodule appeared mixed cystic and solid, hypoechoic, not taller than wide, with ill-defined margins and peripheral calcifications (ACR TI-RADS risk category: TR4). Nuclear medicine thyroid uptake scan demonstrated focally increased activity in the right lower pole corresponding with her right inferior thyroid nodule seen on ultrasound. Remainder of the gland appeared suppressed. She was recommended for ultrasound-guided fine needle aspiration biopsy of her right inferior thyroid nodule, given concerning characteristics on ultrasound findings despite results consistent with a hot nodule. Timing of her antiplatelet therapy was coordinated with her cardiologist, and her biopsy procedure scheduled after she stopped dual antiplatelet therapy. Her FNA results showed clusters of follicular cells with nuclear and architectural atypia, suspicious for papillary thyroid carcinoma. She underwent right thyroid lobectomy. Surgical pathology revealed 2 foci of papillary thyroid carcinoma, follicular variant (2.0 cm, 0.1 cm) and confined to the thyroid. All regional lymph nodes were negative for tumor. Methimazole was discontinued post-operatively, and she started Levothyroxine suppression therapy. Discussion: We present a rare association of papillary thyroid carcinoma presenting as a hot thyroid nodule. Though uncommon, detection of a hyperfunctioning thyroid nodule does not exclude the possibility of thyroid carcinoma and warrants careful evaluation. Clinicians should retain a high index of suspicion particularly when ultrasonography demonstrates findings suspicious for malignancy and consider additional evaluation with fine needle aspiration. Reference: (1) Haugen BR, Alexander EK, Bible KC et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. Presentation: 6/2/2024

6925 A Rare Case of Metastatic Papillary Thyroid Carcinoma Confined to Cervical Lymph Node with No Identifiable Primary Tumor In The Thyroid Gland. A Diagnostic Conundrum

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Papillary thyroid carcinoma (PTC) is the most common treatable thyroid cancer (TC) with very good prognosis. Metastatic PTC either in the lymph node LN or extra-nodal with no primary thyroid lesion identified is a rare phenomenon referred to as occult thyroid carcinoma (OTC). Despite its rarity, it is reported and constitute a diagnostic conundrum. herein we present a case of metastatic PTC identified in cervical lymph nodes (LN) without a primary tumor in the thyroid gland confirmed with surgical pathology. Case Presentation: A 43-year-old female with history of post-ablative hypothyroidism after treatment of toxic nodular goiter for 10 years, with no family history of thyroid cancer presented with incidentally found left 1.8 Heterogeneous hypoechoic solid nodule with lobulated borders and internal calcifications along with left-sided 0.8 LN without normal fatty hilum on Ultrasound Head and Neck. Fine needle aspiration of the left thyroid nodule and suspicious LN revealed PTC in the left LN though the thyroid nodule sample was non-diagnostic. CT of head and neck showed partially calcified thyroid nodule, Hyperattenuating 8 mm left III LN without fatty hilum, and 9 mm left II calcified LN. Patient underwent total thyroidectomy, central neck, and left lateral neck dissection. Surgical pathology showed no malignancy in thyroid gland or central LNs and 1 out 5 LN of the left neck dissection showed PTC with tumor grading of pT0 pN1b pMNA. patient underwent whole-body thyrogen-stimulated thyroid scan which showed iodine avid tissue in the thyroid bed followed by high-dose I-131 radioactive iodine ablation (RAI). Discussion: OTC refers to impalpable incidental TC less than 10 mm per the WHO. Boucek et al classify OTC into four categories, recently a fifth category was added, in which metastasis is confirmed either in regional LN or distant metastasis though thyroid tissue is confirmed to be benign per pathology and imaging evaluation, our patient falls in the fifth category. Hypothesis of this phenomenon is not well understood, one suggested explanation is missed diagnosis due to not enough sample or if lesion is less than 3 mm. another hypothesis is tumor spontaneous regression, or regression secondary to treatment that was inadequate to treat the systemic process of the tumor, which we believe our patient fits in this hypothesis, given that she underwent RAI ablation many years ago. Tumor regression is very rare and reported to be 1 in 140,000 cases. Another theory suggests that PTC can arise in ectopic thyroid tissue. This case is to shed light on a rare clinical and pathological entity to avoid missed diagnoses. Prognosis depends on the extent of metastasis, with favorable one when it is limited to regional LN and worse with distant metastasis. More cases reports are warranted to help guide further management of such cases due to the lack of available guidance in use of RAI surveillance and ablation. Presentation: 6/1/2024