Node Metastasis Research Articles

Inhibition of Colon Cancer Xenograft Growth by Celecoxib Analog OSU-03013 Through Wnt/β-Catenin Pathway Modulation

OSU-03013 is a Celecoxib analog that dose not inhibit COX-2 expression. OSU-03013 effectively mimics the anti-tumor effects of Celecoxib, however, its exact mechanism in colon cancer (CC) is unknown. SW480 cells were injected subcutaneously into the axilla of nude mice until the volume of the transplanted tumor reached 80 mm3. SW480 cells were inoculated into the tail vein of nude mice to establish a liver metastasis model of CC. OSU-03013 was administered by gavage. The pathology of the tumor tissues was assessed using HE staining and cell apoptosis was measured using TUNEL staining. EMT markers in the tumors were determined using Western Blot, and IL-1β and TNF-α were determined using ELISA. VEGF-A and VEGFR-2 in tumor tissues were measured to assess angiogenesis using immunofluorescence. HE staining was conducted to detect the effect of OSU-03013 on liver metastasis. Western Blot assay was performed to determine the expression of Wnt2, β-catenin and GSK-3β. OSU-03013 reduced inflammatory cell infiltration and inhibited IL-1β and TNF-α production by modulating the Wnt/β-catenin pathway. OSU-03013 induced apoptosis of cancer cells in tumor tissues and possessed anti-angiogenic activity. OSU-03013 treatment reduced the number and size of metastatic nodules of cancer cells in liver tissues. OSU-03013 may inhibit tumor growth and angiogenesis through the Wnt3a/β-catenin pathway in CC nude mice.

Mammary carcinoma in a male cat following long-term medroxyprogesterone acetate treatment: case report and review of the literature.

In male cats, as in men, mammary carcinomas are rarely reported. However, like in females, hormonal therapy is a significant risk factor. This study reports the case of an 11-year-old male cat with multiple mammary tumours and a history of long-term medroxyprogesterone acetate therapy for the suppression of sexual behaviour, along with a brief review of the literature. Complete surgical removal of the right mammary chain and the ipsilateral inguinal lymph nodes was performed, and all tissues were submitted for histology. Histological examination revealed the presence of a tumour in the third and fourth mammary glands, consisting of neoplastic cells arranged in various structures, including tubulopapillary and tubular structures, sometimes cystically dilated, and solid areas. The inguinal lymph nodes were also involved. The morphology was consistent with a diagnosis of mammary carcinoma, tubulopapillary type, with nodal metastases. Immunohistochemistry revealed that tumour cells were positive for cytokeratin (clones AE1/AE3), while stromal cells were positive for vimentin (clone V9). The proliferation marker Ki-67, evaluated on both the primary tumour and the nodal metastases, was strongly expressed in the nuclei of neoplastic cells, with a Ki-67 proliferation index of 8.9% and 20% for the primary tumour and the metastases, respectively. This case highlights the importance of considering the possibility of malignant mammary tumours not only in female but also in male cats with a history of long-term hormonal treatment for suppression of sexual behaviour.

Sequential therapy for extramedullary plasmacytoma of the palate: a rare case report with seven years of follow-up and literature review

BackgroundExtramedullary plasmacytoma (EMP) is a rare solitary malignancy that accounts for 3% of plasma cell neoplasms, and EMP with a primary occurrence in the palate is extremely uncommon. Owing to the long course of EMP and the limited available data on treatment outcomes, there are no definitive guidelines for its management, especially for high-risk patients who are more susceptible to early progression to multiple myeloma.Case presentationIn this study, we review nine relevant studies and describe a 54-year-old woman who presented with an asymptomatic nonulcerative mass localized in the palate. After initial radical surgical resection of the lesion, the patient was definitively diagnosed with EMP with minimal plasmacytosis in the bone marrow, and adjuvant intensity-modulated radiation therapy with a minimum dose of 39.6 Gy was administrated in the surgical area. There was no evidence of local recurrence, nodal metastasis or progression to multiple myeloma (MM) during the seven-year follow-up period.ConclusionGiven the atypical clinical features of palate EMP reported in the literature and the encouraging results of our patient, sequential therapy involving surgery and adjuvant radiotherapy for primary palatal lesions in high-risk EMP patients without nodal involvement could be an effective treatment modality.

Long-term outcome of the Milano-HART strategy for high-risk medulloblastoma, including the impact of molecular subtype.

We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, MYC/MYCN amplification. Patients over 3-years-old received,after surgery,staging and histo-biological analysis,sequential high-dose-methotrexate(HD-MTX),high-dose-etoposide(HD-VP16),high-dose-cyclophosphamide(HD-Cyclo),high-dose-carboplatin(HD-Carbo).Hyperfractionated-accelerated-radiotherapy-craniospinal(HART-CSI),administered in twice daily 1.3 Gy-fractions reached a total dose tailored to the patients' age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease,39 Gy in other/older patients.Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy,respectively,but avoided if metastatic nodules were very big or patients very young.Two courses of high-dose-thiotepa were delivered in case of not CR/PR after pre-radiotherapy(RT) phase and in all M0 patients either - pre/post HART.Subgrouping was performed where tissue was available. Eighy-nine patients were enrolled,median age 8.8 years,median follow up 136 months.Overall-survival(OS) and event-free-survival(EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively;5/28 fatal events were not related to relapse(three developed secondary malignancies).Sex,age less than 10 years,histological subtype,presence of MYC/MYCN amplification,reduction in CSI dose,omission of RT-boosts,implementation of myeloablative therapy,presence/absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P<0.001).Subgrouping in 66/89 patients' samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) vs. group 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response. This strategy, partly adopted in the ongoing SIOPE protocol,confirmed improved EFS and OS over previously reported outcomes in all high-risk categories;SHH tumors appeared the most aggressive.

Diagnostic performance of simultaneous PET-magnetic resonance versus PET-computed tomography in oncology with an overview on clinical utility and referral pattern of PET-magnetic resonance: a single institutional study.

PET-magnetic resonance (PETMR) imaging is an upcoming investigative modality with a few installations in Asia and only three in India. PET-Computed tomography (PETCT) is an established diagnostic cornerstone for oncological indications but with limited resolution for small lesions due to low soft-tissue contrast and additional radiation exposure. Our primary objective was to evaluate the diagnostic performance of simultaneous PETMR and PETCT in lesion detection in oncological practice. Secondly to assess the referral pattern and study the clinical utility of PETMR in a university hospital practice. A total of 100 consecutive biopsy-proven cancer patients (breast or lung malignancy with suspected metastases) underwent 18F fluorodeoxyglucose (FDG) PETMR and PETCT for staging as a single injection, double examination protocol. Morphological lesion detection on correlative imaging/histopathology was used as the gold standard. Analysing the referral pattern, a total of 9366 patients underwent simultaneous PETMR imaging for indications in the past 5 years since installation. 18F FDG PETMR detected 100% of primary tumours in breast/lung carcinoma (Ca) patients while PETCT was positive in 96%. Overall accuracy of nodal metastases detection for PETMR and PETCT was 96 and 88%, while for distant metastases the accuracy was 100 and 93%, respectively. FDG PETMR proved more sensitive and specific than PETCT for regional nodal (P = 0.011 and P < 0.001) and distant metastases detection (P = 0.017 and P < 0.001, respectively). Analysing the general referral pattern for PETMR, the majority were oncology referrals (66.5, 33.5%) when compared to nononcological indications. About 66.24% were FDG based, followed by Ga prostate-specific membrane antigen and dodecane tetraacetic acid. The general utility of PETMR was found incremental in better delineation of small lesions especially in head, neck, liver, brain and gynaecological malignancies. In our past 5 years of PETMR practice, we found that simultaneous PETMR is a highly recommended ideal imaging technique for oncological and nononcological indications. It has excellent diagnostic performance with high sensitivity, specificity and accuracy when compared to PETCT in tumour, nodal metastases staging in specific subgroup of breast and lung malignancy patients.

Determinants of Prognosis in Head and Neck Cutaneous Squamous Cell Carcinoma With Nodal Metastases

The eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE). To identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease. This retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients. Curative intent surgery ± adjuvant radiotherapy. Differences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis. Among 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (>3-6 cm vs ≤3 cm [HR, 1.41; 95% CI, 1.03-1.93]; >6 cm vs ≤3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; ≥5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors. The study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.

MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle-invasive bladder cancer.

Loss of heterozygosity in chromosome 9p21, common in urothelial carcinoma (UC), typically involves deletion of CDKN2A and MTAP genes. MTAP loss is emerging as a promising therapeutic target and predictive biomarker in UC. This single-centrre retrospective study examined the incidence of CDKN2A deletions and MTAP loss in muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma (mUC), investigating their correlations with clinical, pathological, and genomic features, as well as patient outcomes. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on 302 MIBC specimens and 63 biopsy-proven metachronous urothelial metastases to assess CDKN2A deletions and MTAP protein expression. CDKN2A homozygous deletion (HD), identified in 30.3% of MIBCs, and MTAP loss, found in 28.8% of MIBCs, were both significantly associated with the luminal-URO subtype, FGFR3 mutations, and normal/wildtype p53 IHC (P < 0.05). Loss of MTAP expression was significantly correlated with CDKN2A HD, with 84.0% sensitivity, 92.3% negative predictive value (NPV), 96.3% specificity, and 91.9% positive predictive value (PPV). MTAP expression was 100% concordant between primary tumours and nodal metastases. Patients with MTAP loss had a higher incidence of visceral metastases (50%) compared to bone/soft tissue (35.7%) and nodes (14.3%). Mean progression-free survival and overall survival were shorter for patients with MTAP loss, although not statistically significant. Our findings highlight CDKN2A HD and MTAP loss as prevalent genetic alterations in MIBC and mUC, particularly within the luminal-URO subtype and FGFR3-mutated, p53-normal/wildtype tumours. MTAP IHC can serve as a surrogate marker for 9p21.3 HD, highlighting its clinical relevance and potential as a therapeutic target and predictive biomarker in MIBC.

Head-to-Head Comparison of the Diagnostic Performance of FDG PET/CT and FDG PET/MRI in Patients With Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND. The available evidence on the use of FDG PET/MRI performed using an integrated system in patients with cancer has grown substantially. OBJECTIVE. The purpose of this study was to perform a systematic review and meta-analysis comparing the diagnostic performance of FDG PET/CT and FDG PET/MRI in patients with cancer. EVIDENCE ACQUISITION. MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched for studies reporting a head-to-head comparison of the diagnostic performance of FDG PET/CT and FDG PET/MRI in patients with cancer from July 1, 2015, to January 25, 2023. The two modalities' diagnostic performance was summarized, stratified by performance end point. For end points with sufficient data, a meta-analysis was performed using bivariate modeling to produce summary estimates of pooled sensitivity and specificity. For the remaining end points, reported performance in individual studies was recorded. EVIDENCE SYNTHESIS. The systematic review included 29 studies with a total of 1656 patients. For patient-level detection of regional nodal metastases (five studies), pooled sensitivity and specificity for PET/MRI were 88% (95% CI, 74-95%) and 92% (95% CI, 71-98%), respectively, and for PET/CT were 86% (95% CI, 70-94%) and 86% (95% CI, 68-95%). For lesion-level detection of recurrence and/or metastases (five studies), pooled sensitivity and specificity for PET/MRI were 94% (95% CI, 78-99%) and 83% (95% CI, 76-88%), respectively, and for PET/CT were 91% (95% CI, 77-96%) and 81% (95% CI, 72-88%). In individual studies not included in the meta-analysis, PET/MRI in comparison with PET/CT showed staging accuracy in breast cancer of 98.0% versus 74.5% and in colorectal cancer of 96.2% versus 69.2%; sensitivity for primary tumor detection in cervical cancer of 93.2% versus 66.2%; and sensitivity, specificity, and accuracy for lesion-level liver metastasis detection of 91.1-98.0% versus 42.3-71.1%, 100.0% versus 83.3-98.6%, and 96.5-98.2% versus 44.7-86.7%, respectively. In three studies, management was more commonly impacted by information from PET/MRI (5.2-11.1%) than PET/CT (0.0-2.6%). CONCLUSION. PET/MRI showed comparable or superior diagnostic performance versus PET/CT across a range of cancers and end points. CLINICAL IMPACT. The findings help to identify clinical settings where PET/MRI may provide clinical benefit for oncologic evaluation. TRIAL REGISTRATION. Prospective Register of Systematic Reviews CRD42023433857.

Prediction of High Nodal Burden in Patients With Sentinel Node–Positive Luminal ERBB2-Negative Breast Cancer

In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment. To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND. The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024. Predictors of high nodal burden. High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration. Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83). The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed. ClinicalTrials.gov Identifier: NCT02240472.

99mTc-FAPI-04 SPECT/CT outperforms contrast-enhanced CT in detecting metastasis in postoperative patients with colorectal cancer.

To compare the performance of 99mTc-FAPI-04 SPECT/CT and contrast-enhanced CT (CECT) in the detection of postoperative metastasis in patients with colorectal cancer (CRC). The postoperative patients with CRC were consecutively recruited from January 2023 to June 2023, and the enrolled patients completed 99mTc-FAPI-04 SPECT/CT imaging and CECT examination within two weeks. Histopathological analysis and the follow-up results were used as the reference criteria. The location and number of metastatic sites and the detection accuracy between the two imaging methods were compared. The tumor-to-background ratio (TBR) of liver metastasis and lymph node metastasis in 99mTc-FAPI-04 SPECT/CT imaging were also calculated for comparison. In total, 19 postoperative CRC patients, including 15 patients with metastasis, were included in this study. In the patient-based analysis, 99mTc-FAPI-04 SPECT/CT showed a significantly higher sensitivity for the detection of metastasis than CECT (93.3% vs. 80.0%, p = 0.038), but both techniques had the same specificity (100%, 4/4). For the lesion-based analysis, the detection rates of metastatic sites were 92.2% (47/51) and 72.5% (37/51) for 99mTc-FAPI-04 SPECT/CT and CECT, respectively, and the difference between them was statistically significant. In the diagnosis of liver metastasis and lymph node metastasis, 99mTc-FAPI-04 SPECT/CT both exceeded CECT. Additionally, the TBR in lymph node metastasis was higher than that in liver metastasis. The findings suggested that 99mTc-FAPI-04 SPECT/CT could detect metastasis more effectively than CECT, especially liver and lymph node metastases, in postoperative CRC patients.

Clinicoradiographic Examination Versus Histopathological Evaluation in Detection and Staging of Cervical Nodal Metastasis in Oral Squamous Cell Carcinoma Patients in Sudan

Clinicoradiographic Examination Versus Histopathological Evaluation in Detection and Staging of Cervical Nodal Metastasis in Oral Squamous Cell Carcinoma Patients in Sudan

Optimizing the Sensitivity of a Pelvic Sentinel Node Algorithm Requires a Hybrid Algorithm Combining Indocyanine Green Based Mapping and the Removal of Non-Mapped Nodes at Defined Anatomic Positions.

to investigate the incidence of non-mapped isolated metastatic pelvic lymph nodes at pre-defined anatomical positions. Between June 2019 and January 2024, women with uterine-confined endometrial cancer (EC) deemed suitable for robotic surgery and the detection of pelvic sentinel nodes (SLNs) were included. An anatomically based, published algorithm utilizing indocyanine green (ICG) as a tracer was adhered to. In women where no ICG mapping occurred in either the proximal obturator and/or the interiliac positions, defined as "typical positions", those nodes were removed and designated as "SLN anatomy". Ultrastaging and immunohistochemistry were applied to all SLNs. The proportion of isolated metastatic "SLN anatomy" was evaluated. A non-mapping of either the obturator or interiliac area occurred in 180 of the 620 women (29%). In total, 114 women (18.4%) were node-positive and five of these women (4.3%) had isolated metastases in an "SLN anatomy", suggesting a similar lower sensitivity of the ICG-only algorithm. In an optimized SLN algorithm for endometrial cancer, to avoid undetected nodal metastases in 4.3% of node-positive women, if mapping fails in either the proximal obturator or interiliac area, nodes should be removed from those defined anatomic positions, despite mapping at other positions.

Novel Nomogram for Prediction of Lymph Node Metastases from Buccal Mucosa Squamous Carcinoma Using Histological Parameters

Objective The aim of the study was to construct a nomogram that is easily reproducible, accurate, and cost-effective in predicting cervical lymph nodal metastasis in buccal mucosa cancer. Methodology Patients who underwent radical resection of a primary tumor of the buccal mucosa with neck dissection were enrolled. Clinical characteristics independently associated with lymph nodal metastasis in multivariate analyses were adopted to build the model. Results Patients who underwent surgery (January 2021–December 2021) were included as the model development cohort (n = 127). Depth of invasion, perineural invasion, lymphovascular invasion, and the worst pattern of invasion were independent predictors of lymph nodal metastasis. The nomogram model based on these four predictors showed good discrimination accuracy in percentage prediction of lymph nodal metastasis. Conclusion This study proposes a simple predictive model for the risk of nodal metastasis in buccal mucosa squamous cell cancer. The study has strength that, it is based on a large sample, proposed model being simple size, and based on parameters empirically supported as well as established in literature, easy to use in routine clinical practice, and cost-effective.

Comprehensive analysis of clinicopathological characteristics in oral squamous cell carcinoma arising from oral submucous fibrosis: a retrospective study

BackgroundOral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics.MethodsA retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification.ResultsWe found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs.ConclusionIn this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

Incorporation of pre- and intra-operative sentinel lymph node mapping techniques in dogs with apocrine gland anal sac adenocarcinoma

The high incidence of nodal metastasis, variable lymphatic drainage patterns, and prognostic significance of nodal metastasis in dogs with apocrine gland anal sac adenocarcinoma (AGASACA) highlight the need for development of standardized techniques for lymph node staging in canine AGASACA. The aim of this study was to develop and describe the utility of pre- and intra-operative sentinel lymph node (SLN) mapping techniques for subsequent nodal extirpation and histologic assessment in dogs with AGASACA. A prospective clinical trial was performed as a pilot study. Eight client-owned dogs with unilateral AGASACA were enrolled. Preoperative contrast-enhanced ultrasound (CEUS) via transrectal ultrasound (TRUS) and CT-lymphography (CTL) was followed by intraoperative SLN mapping within 7 days utilizing a visible dye (methylene blue [MB]) and a near-infrared (NIR) fluorescent dye (indocyanine green [ICG]) with subsequent nodal extirpation and routine anal sacculectomy. In all dogs, preoperative CTL and intraoperative SLN mapping identified at least one SLN. Pre- and intra-operative findings differed in 4/8 dogs. Preoperative CEUS identified a SLN in 7/8 dogs, but the exact location of the SLN was indeterminate. Extirpated lymph nodes were metastatic in 2/8 dogs. Preoperative CTL and intraoperative MB and ICG were an effective combination of SLN mapping techniques in dogs with AGASACA. These techniques each provided unique advantages. Combined, they identified and guided extirpation of early metastatic lymph nodes. Large-scale, prospective studies utilizing the techniques described are needed to accurately determine the incidence and significance of early/occult nodal metastasis in canine AGASACA.

Semi-supervised ViT knowledge distillation network with style transfer normalization for colorectal liver metastases survival prediction

Colorectal liver metastases (CLM) affect almost half of all colon cancer patients and the response to systemic chemotherapy plays a crucial role in patient survival. While oncologists typically use tumor grading scores, such as tumor regression grade (TRG), to establish an accurate prognosis on patient outcomes, including overall survival (OS) and time-to-recurrence (TTR), these traditional methods have several limitations. They are subjective, time-consuming, and require extensive expertise, which limits their scalability and reliability. Additionally, existing approaches for prognosis prediction using machine learning mostly rely on radiological imaging data, but recently histological images have been shown to be relevant for survival predictions by allowing to fully capture the complex microenvironmental and cellular characteristics of the tumor. To address these limitations, we propose an end-to-end approach for automated prognosis prediction using histology slides stained with Hematoxylin and Eosin (H&E) and Hematoxylin Phloxine Saffron (HPS). We first employ a Generative Adversarial Network (GAN) for slide normalization to reduce staining variations and improve the overall quality of the images that are used as input to our prediction pipeline. We propose a semi-supervised model to perform tissue classification from sparse annotations, producing segmentation and feature maps. Specifically, we use an attention-based approach that weighs the importance of different slide regions in producing the final classification results. Finally, we exploit the extracted features for the metastatic nodules and surrounding tissue to train a prognosis model. In parallel, we train a vision Transformer model in a knowledge distillation framework to replicate and enhance the performance of the prognosis prediction. We evaluate our approach on an in-house clinical dataset of 258 CLM patients, achieving superior performance compared to other comparative models with a c-index of 0.804 (0.014) for OS and 0.735 (0.016) for TTR, as well as on two public datasets. The proposed approach achieves an accuracy of 86.9% to 90.3% in predicting TRG dichotomization. For the 3-class TRG classification task, the proposed approach yields an accuracy of 78.5% to 82.1%, outperforming the comparative methods. Our proposed pipeline can provide automated prognosis for pathologists and oncologists, and can greatly promote precision medicine progress in managing CLM patients.

Artificial Intelligence Algorithm Can Predict Lymph Node Malignancy from Endobronchial Ultrasound Transbronchial Needle Aspiration Images for Non-Small Cell Lung Cancer

Introduction: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) for lung cancer staging is operator dependent, resulting in high rates of non-diagnostic lymph node (LN) samples. We hypothesized that an artificial intelligence (AI) algorithm can consistently and reliably predict nodal metastases from the ultrasound images of LNs when compared to pathology. Methods: In this analysis of prospectively recorded B-mode images of mediastinal LNs during EBUS-TBNA, we used transfer learning to build an end-to-end ensemble of three deep neural networks (ResNet152V2, InceptionV3, and DenseNet201). Model hyperparameters were tuned, and the optimal version(s) of each model was trained using 80% of the images. A learned ensemble (multi-layer perceptron) of the optimal versions was applied to the remaining 20% of the images (Test Set). All predictions were compared to the final pathology from nodal biopsies and/or surgical specimen. Results: A total of 2,569 LN images from 773 patients were used. The Training Set included 2,048 LNs, of which 70.02% were benign and 29.98% were malignant on pathology. The Testing Set included 521 LNs, of which 70.06% were benign and 29.94% were malignant on pathology. The final ensemble model had an overall accuracy of 80.63% (95% confidence interval [CI]: 76.93–83.97%), 43.23% sensitivity (95% CI: 35.30–51.41%), 96.91% specificity (95% CI: 94.54–98.45%), 85.90% positive predictive value (95% CI: 76.81–91.80%), 79.68% negative predictive value (95% CI: 77.34–81.83%), and AUC of 0.701 (95% CI: 0.646–0.755) for malignancy. Conclusion: There now exists an AI algorithm which can identify nodal metastases based only on ultrasound images with good overall accuracy, specificity, and positive predictive value. Further optimization with larger sample sizes would be beneficial prior to clinical application.

Navigating the Diagnosis and Treatment of Extra-Adrenal Pheochromocytoma Presenting with Chronic Abdominal Pain: A Clinical Conundrum

Background: Extra-adrenal pheochromocytomas, or paragangliomas, are rare neuroendocrine tumors that present diagnostic challenges due to their nonspecific symptoms and radiologic features.Objective: To report a case of extra-adrenal pheochromocytoma presenting as chronic abdominal pain and hepatic masses, emphasizing the diagnostic and therapeutic challenges.Methods: A 36-year-old male with a history of diabetes and hypertension presented with weight loss and abdominal pain. Initial evaluation included comprehensive physical examination, laboratory tests, ultrasonography, and CT imaging of the abdomen and chest. Partial hepatectomy was performed, and the diagnosis was confirmed through histopathological and immunohistochemical analysis.Results: Imaging identified three mixed echogenic hepatic masses, with the largest measuring 5.6 x 5.4 cm. Enlarged para-aortic lymph nodes were observed, the largest being 4.0 x 3.5 cm. CT chest revealed a mass on the chest wall (7.0 x 3.0 cm) with metastatic lung nodules. Immunohistochemistry confirmed paraganglioma with positivity for chromogranin A and neuron-specific enolase.Conclusion: This case underscores the importance of considering paragangliomas in differential diagnoses of atypical abdominal masses and highlights the critical role of histopathological confirmation in guiding management.

PLXDC1 serves as a potential prognostic marker and involves in malignant progression and macrophage polarization in colon cancer.

The malignant behavior and immune escape ability of cancer cells lead to therapeutic failure and poor prognosis for patients with various cancers, including colon cancer. Plexin domain containing 1 (PLXDC1) was initially identified to exert key roles in tumor by regulating angiogenesis and has recently proved to be involved in cell proliferation and migration of glioblastoma and gastric cancer cells. However, its roles in colon cancer remain unclear. In this study, the online bioinformatics databases confirmed high expression of PLXDC1 in colon cancer specimens, which was associated with cancer stages and nodal metastasis. Similarly, the increased expression of PLXDC1 was also validated in our collected samples and colon cancer cells. Moreover, patients with high expression of PLXDC1 had shorter survival, indicating that PLXDC1 might be a potential prognostic predictor for colon cancer patients. Notably, targeting PLXDC1 inhibited cancer cell viability and invasion, and enhanced cell apoptosis. Intriguingly, Tumor Immune Estimation Resource database confirmed that PLXDC1 expression was related to various tumor-infiltrating immune cells in colon adenocarcinoma including macrophages, and its expression was also correlated with M2-like macrophage markers. In vitro, colon cancer cells with PLXDC1 downregulation had a reduced ability to recruit and polarize macrophage towards M2 phenotype by decreasing the percentage of CD206+ cells and M2-like markers (CD206, CD163, arginase1, and interleukin 10 [IL-10]). Moreover, PLXDC1 knockdown attenuated M2 macrophage-mediated promotion in cancer cell viability and invasion. Mechanically, inhibition of PLXDC1 suppressed activation of the IL-6/Signal transducer and activator of transcription 3 (STAT3) signaling. Reactivating the above pathway by transfection with IL-6 plasmids reversed the suppressive effects of PLXDC1 knockdown on cancer cell malignant behaviors, macrophage recruitment and M2-like polarization. Thus, PLXDC1 downregulation may inhibit the malignancy of colon cancer cells and their ability to recruit and polarize macrophages towards M2 phenotype by blocking the IL-6/STAT3 pathway. Together, targeting PLXDC1 may attenuate the progression of colon cancer by direct roles in cancer cells and indirect roles in macrophage polarization, representing a promising therapeutic target for colon cancer patients.

Bioinformatic Analysis of IKK Complex Genes Expression in Selected Gastrointestinal Cancers.

Gastrointestinal cancers account for over a quarter of all cancer cases and are associated with poor prognosis and high mortality rates. The IKK complex (the canonical I kappa B kinase), comprising the CHUK, IKBKB, and IKBKG genes, plays a crucial role in activating the NF-kB signaling pathway. This study aimed to analyze publicly available bioinformatics data to elucidate the oncogenic role of IKK genes in selected gastrointestinal cancers. Our findings reveal that IKBKB and IKBKG are significantly upregulated in all examined cancers, while CHUK is upregulated in esophageal carcinoma and stomach adenocarcinoma. Additionally, the expression of IKK genes varies with histological grade and nodal metastases. For instance, in stomach adenocarcinoma, CHUK and IKBKB are upregulated in higher histological grades and greater lymph node infiltration. Lower expression levels of CHUK, IKBKB, and IKBKG in stomach adenocarcinoma and IKBKB in esophageal squamous cell carcinoma correlate with shorter overall survival. Conversely, in esophageal adenocarcinoma, reduced IKBKG expression is linked to longer overall survival, while higher IKBKB expression in colon adenocarcinoma is associated with longer overall survival. Given the significant role of IKK genes in the development and progression of selected gastrointestinal cancers, they hold potential as prognostic markers and therapeutic targets, offering valuable insights for clinical practice.