Carcinoembryonic Research Articles

Co-delivery of Doxorubicin and VEGF siRNA using carcinoembryonic antigen-targeted chitosan nanoparticles for colorectal cancer

Developing a targeted nanocarrier-based therapeutic approach is highly effective in delivering therapeutics to specific cancer cells. Combining two or more therapeutic approaches with different mechanisms of action can effectively maintain their unique benefits while considerably improving cancer treatment. Doxorubicin (DOX) binds to DNA by intercalation and triggers a cascade of biochemical processes in tumor cells leading to death. Anti-VEGF medicines may sensitize cancer cells to chemotherapeutics by limiting blood supply and increasing penetration by disrupting tumor vasculature. In this study, DOX and vascular endothelial growth factor siRNA (VEGF siRNA) loaded chitosan nanoparticles (ChNPs) were prepared by using the ionic gelation method. The DOX-siRNA-ChNPs surface was then functionalized with carcinoembryonic antigen (CEA) targeted monoclonal antibody (DOX-siRNA-ChNPs-CMAb), thereby delivering therapeutic moieties into the cancer milieu. The cytotoxicity and cellular uptake of the developed nanocarrier were tested in-vitro on HT-29, which revealed that DOX-siRNA-ChNPs-CMAb possessed the highest cytotoxicity when compared with other prepared formulations and free DOX. The cellular uptake using fluorescence microscopy displayed a significantly higher uptake of DOX-siRNA-ChNPs-CMAb (targeted) than free DOX and DOX-siRNA-ChNPs (non-targeted). Apoptosis analysis in flow cytometry using annexin-V/PI staining demonstrated a substantially higher apoptosis rate of HT-29 cells using DOX-siRNA-ChNPs-CMAb than DOX-siRNA-ChNPs. Moreover, DOX-siRNA-ChNPs-CMAb were studied in CRC induced animal models, showing that DOX-siRNA-ChNPs-CMAb specifically targets CRC cells without showing organ toxicity. Thus, the novel approach of simultaneous delivery of DOX and siRNA using CMAb conjugated ChNPs demonstrated significant targeting in both in-vitro and in-vivo with minimal organ toxicity.

Effect of elevated CEA levels on the outcome of colorectal cancer patients with different histopathologic types: A SEER population-based study.

Limited and contradictory evidence has been reported regarding the prognostic effects of carcinoembryonic antigen (CEA) on the prognosis and metastasis of classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC) in colorectal cancer patients. We investigated the associations between histological subtypes and preoperative serum CEA levels in determining the oncologic outcomes of colorectal cancer (CRC) patients. A total of 47,692 patients with clearly diagnosed CRC were selected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two cohorts based on serum CEA levels: CEA-normal (C0) and CEA-elevated (C1). Chi-square analysis revealed a correlation between CEA levels and histological classification. We then included a newly defined interaction variable (H&CEA) in the Cox regression analysis, which demonstrated that this variable could serve as an independent prognostic factor (P<0.001). CA, in the context of elevated serum CEA levels, differed from the other two histopathological types, showing unexpectedly higher risks for both OS (HR = 1.70, 95% CI = 1.65-1.75, P<0.001) and CSS (HR = 1.78, 95% CI = 1.72-1.85, P<0.001). Furthermore, elevated CEA levels significantly increased the proportion of liver metastases in the CA group (25.43% vs. 3.95%, P<0.001). The interaction variable H&CEA can be used as an independent prognostic factor for CRC and should be considered in the diagnosis of CRC and the development of personalized treatment plans. Additionally, in the context of elevated CEA levels, CA is associated with poor prognosis and increased liver metastases. This CRC subgroup warrants special clinical attention from oncologists.

The Prospect of Improving Pancreatic Cancer Diagnostic Capabilities by Implementing Blood Biomarkers: A Study of Evaluating Properties of a Single IL-8 and in Conjunction with CA19-9, CEA, and CEACAM6.

Background/Objectives: This study aims to evaluate the possible clinical application of interleukin 8 (IL-8) as a single biomarker and its capabilities in combination with carbohydrate antigen (CA19-9), carcinoembryonic antigen (CEA), and carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as diagnostic and prognostic tools for pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 170 serum samples from patients with PDAC (n = 100), chronic pancreatitis (CP) (n = 39), and healthy individuals (n = 31) were analysed. IL-8 and CEACAM6 were measured by an enzyme-linked immunosorbent assay (ELISA). CA19-9 and CEA were determined by chemiluminescent microparticle immunoassay, and bilirubin was quantified using a diazonium salt reaction. Receiver operating characteristic curve analysis, logistic regression, and Kaplan-Meier analyses were performed to evaluate the properties of a single IL-8 and in combination with other biomarkers. Results: The concentrations of IL-8 were statistically significantly higher in the PDAC group compared to the CP and control groups. Heterogeneous levels of IL-8 correlated with PDAC stages (p = 0.007). IL-8 had good and satisfactory diagnostic efficacy in differentiating PDAC from controls (0.858; p < 0.001) and patients with CP (0.696; p < 0.001), respectively. High and low expressions of IL-8 were not significantly associated with overall survival (OS) or disease-free survival (DFS). A combination of IL-8, CEACAM6, and CA19-9 reached the highest AUC values for differentiating PDAC from the control group. The best classification score between PDAC and the control group with CP patients was obtained by merging IL-8 and CA19-9 (0.894; p < 0.001). Conclusions: These results provide compelling evidence of IL-8 as a promising diagnostic biomarker. Nonetheless, due to the high complexity of PDAC, only the conjunction of IL-8, CA19-9, and CEACAM6 integrates sufficient diagnostic capabilities.

Prognostic value of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with obstructive colorectal cancer treated with a self-expandable metallic stent and curative surgery.

The importance of tumor markers is well established; yet little is known about their prognostic value for patients with obstructive colorectal cancer (OCRC). We investigated the clinical significance of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with non-metastatic OCRC, who underwent insertion of a self-expandable metallic stent and curative surgery. Clinical data on 91 patients with OCRC were analyzed retrospectively to evaluate the associations of preoperative serum values of tumor makers with short- and long-term outcomes. The 91 patients comprised 53 men and 38 women, with a median age of 71years. Twelve patients had an elevated preoperative CA 19-9 level. Multivariate analyses revealed that an elevated CA 19-9 level was independently associated with poor disease-free survival (DFS) [hazard ratio (HR) = 4.57, 95% confidence interval (CI) 2.06-10.14, P < 0.001] and overall survival (HR = 4.06, 95% CI 1.46-11.24, P = 0.007). A CEA level > 5ng/ml had no prognostic value, whereas a CEA level > 10.8ng/ml was significantly associated with worse DFS (P = 0.032). Measuring the CA 19-9 level concomitantly with the CEA level for patients with advanced CRC, including OCRC, may provide a valuable means to improve prognostication.

The Effect of the Adoption of the National Accreditation Program for Rectal Cancer Process on Compliance Standards at a Single Institution.

Background: The National Accreditation Program for Rectal Cancer (NAPRC) was developed to enhance the quality of rectal cancer care in the United States. This project compared NAPRC compliance at a single tertiary care academic hospital before and after the institution adopted these standards in 2019. Methods: Rectal cancer patients from 2016 to 2023 who met NAPRC eligibility criteria were retrospectively reviewed for compliance with pre-selected patient care standards. Patients diagnosed prior to August 1, 2019 (pre-NAPRC) were compared with those diagnosed afterward (post-NAPRC) to determine whether compliance with these standards differed following the institution's adoption of new guidelines. Results: This study included 353 patients, 146 pre-NAPRC and 207 post-NAPRC. The post-NAPRC group demonstrated significantly higher compliance with pretreatment standards compared to the pre-NAPRC group, including attaining magnetic resonance imaging (MRI) (P = .015), computed tomography (CT) (P < .001), and a carcinoembryonic antigen (CEA) level (P < .001). Postoperative standards were more frequently met in the post-NAPRC group regarding the photographing of surgical specimens (P < .001). No significant differences were observed in confirming a tissue diagnosis, starting treatment within a 60-day timeframe, or completing surgical pathology reports. Prior to initiation of the NAPRC process, the institution had achieved accreditation-level compliance in 2 of the 7 standards. Within 2years of adopting NAPRC standards, complete compliance was met in 6 of the 7 measures. Conclusions: A single institution's adoption of NAPRC standards improved compliance with multiple rectal cancer care standards, achieving near-complete accreditation level compliance within 2years.

Staging Paradox and recurrence pattern among stage IIB, IIC, and IIIA Colon cancers: a retrospective cohort study

PurposeThe survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database.MethodsPatients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined.ResultsA total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis.ConclusionsBased on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer.

Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.

An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.

High levels of autotaxin and lysophosphatidic acid predict poor outcome in treatment of resectable gastric carcinoma

BackgroundAlthough early-stage gastric cancer is a candidate for curative surgical resection, the absence of specific early symptoms results in a late diagnosis and consequently most patients present advanced or metastatic disease. Identifying noveland tumor-specific biomarkers is needed to increase early detection and match patients to the appropriate treatment. The present study focused on the possible prognostic role of Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2)/Autotaxin (ATX) and lysophosphatidic acid (LPA) in Gastro-Esophageal Adenocarcinoma (GEA). High levels of ATX/LPA are associated with several malignancies including gastrointestinal tumors. MethodsUsing a bioinformatics analysis, the incidence of ENPP2 mutations together with its expression in the tumor tissues and the correlation between the presence of mutations and the survival rate were examined in databases of GEA patients. Furthermore, circulating levels of ATX and LPA were studied retrospectively and longitudinally both in patients receiving frontal surgery and in patients receiving preoperative chemotherapy. ResultsOverall findings suggested that although ENPP2 mutations occur at low incidence, their presence was associated with a particular poor Overall Survival (OS). Furthermore, removal of the tumour by surgery resulted in a decrease in serum ATX and LPA levels within five days, regardless of any previous chemotherapy. Basal circulating ATX were associated with the aggressive diffuse GEA and could be considered of negative prognostic value, mainly in combination models with circulating Carcino-Embryonic Antigen (CEA). ConclusionsBased on these observations, clinical trials with ATX-targeted drugs and standard chemotherapy regimens may benefit from selecting GEA patients based on their levels of ATX, LPA and CEA.

Development and validation of a prediction model for gastric cancer: a single-center prospective study.

This study aimed to develop and validate a novel nomogram for diagnosing gastric cancer (GC). In this prospective analysis, 146 patients of Wenzhou Central Hospital were recruited for a GC group and a benign lesion group and were divided into a training set and an internal validation set in a ratio of 7:3. Clinical and analytical characteristics were collected and analyzed by logistic regression analysis. The performance of the predictive model was evaluated using the receiver operating characteristic curve, calibration curve, and decision curve analysis. There were 5 variables, namely albumin, carcinoembryonic antigen, carbohydrate antigen 125, creatinine, and small proline-rich protein 2A, that were identified as the final parameters for the developed model. In the training and internal validation sets, the area under the curve of the model was 0.968 and 0.979, respectively, showing good diagnostic performance. This study developed and validated a new nomogram based on 5 parameters. This model shows good diagnostic performance in distinguishing GC from benign lesion groups and has certain significance in clinical application.

An epitope imprinted electrochemical sensor for highly sensitive and selective determination of prostate-specific antigen.

Asimple method forhighly selective and sensitive prostate-specific antigen (PSA) detection using a molecularly imprinted electrochemical sensor ispresented. The sensor was developed through an epitope imprinted strategy combined with electrochemical measurement techniques. An epitope molecularly imprinted polymer (EMIP) film was constructed on a AuNPs-coated gold electrode surface through electropolymerization, utilizing the C-terminus epitope of PSA (KWIKDTIVANP) as the template molecular and o-phenylenediamine as the functional monomer. The characteristics of EMIP film were investigated by using a scanning electron microscope and electrochemical test methods, including electrochemical impedance spectroscopy and cyclic voltammetry. Key parameters such as electropolymerization cycles, elution and rebinding times, and the molar ratio of template molecular to functional monomer were systematically optimized. The sensor demonstrated a detection limit (LOD) of 0.31 fg/mL and exhibited an excellent linear response towards PSA concentration ranging from 1.0 fg/mL to 0.1 µg/mL. Furthermore, the EMIP sensor showed excellent selectivity against other biological macromolecules, such as bovine serum albumin, human serum albumin, alpha-fetoprotein, and carcinoembryonic antigen. With recoveriesbetween 95.89 and 106.04% for PSA detection in human serums theEMIP/AuNPs/AuE electrochemical sensor showed great potential in real sample analysis.

A fluorescent platform integrated with a “one-pot” nicking endonuclease signal amplification and magnetic separation for simultaneous detection of tumor markers

Although Enzyme-linked immunosorbent assay (ELISA) has been widely used for biomedical research, simultaneous sensitive and cost-effective detection of multiple biomarkers is challenging. Herein, we proposed a “one-pot” nicking endonuclease signal amplification (NESA)-based fluorescent aptasensor for simultaneous detection of carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP). Firstly, two aptamers were synchronously immobilized on the surface of magnetic nanoparticles (MNPs) by coupling with two complementary DNA (cDNA). CEA and AFP specifically recognized the aptamers and then the released cDNA (ssDNA) from the double-strands (dsDNA) triggers NESA, further breaking two detection probes which were labeled with the fluorescent dye (FAM and ROX) and its quencher (BHQ1 and BHQ2) at the same time. Then, the fluorescence signal of FAM and ROX were restored separately. The results indicated that the fluorescence intensity at the emission wavelength of 518 nm and 610 nm had a positive correlation with CEA and AFP concentrations, respectively. Under the optimum conditions, wider liner range of 1–500 ng mL−1 to CEA and 5–800 ng mL−1 to AFP of this fluorescent aptasensor were successfully obtained, achieving a detection limit of CEA and AFP were 0.7 ng mL−1 and 2 ng mL−1, respectively. Hence, it turned out that the aptasensor strategy can be a promising candidate for developing a newly fluorescence assay for the simultaneous quantitative detection of multiple tumor markers in matrix samples by changing the corresponding sequences of aptamer and fluorescent signal probe, which has great potential for the screening of early cancer.

Novel anti-CEA affibody for rapid tumor-targeting and molecular imaging diagnosis in mice bearing gastrointestinal cancer cell lines.

Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (ZCEA539, ZCEA546, and ZCEA919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled ZCEA affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled ZCEA affibody exhibited high tumor-targeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of ZCEA affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer.

Examination of Sarcopenia with Obesity as a Prognostic Factor in Patients with Colorectal Cancer Using the Psoas Muscle Mass Index

Background: Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods: We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results: CRRFS was significantly shorter in the SO group than in the non-SO group (p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions: Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients.

Development and validation of a relatively accurate gastric cancer high-risk group screening scoring system in urban residents.

Our study aimed to develop a relatively accurate gastric cancer (GC) screening score system for urban residents and to validate the screening efficacy. The present study included a derivation cohort (n = 3406) and a validation cohort (n = 868) of urban residents. Applying the full-stack engineering intelligent system platform of Hualian Health Big Data of Shandong University, the clinical physical examination data of subjects were collected. Univariate and multivariate analyses were used to identify risk factors for GC, and subsequently, an optimal prediction rule was established to create three distinct scoring systems. In the GC-risk scoring system I, age, plateletocrit (PCT), carcinoembryonic antigen (CEA), glucose, albumin, creatinine were independent risk factors of GC, with scores ranging from 0 to 28 and optimal cut-off was 15.5. The second scoring system consisted of age, PCT, RDW-CV, CEA, glucose, albumin, and creatinine, with scores ranging from 0 to 31. The optimal cut-off point was determined to be 15.5. The scoring system III comprise of age, sex, PCT, RDW CV, CEA, glucose, with scores ranging from 0 to 21 and optimal cut-off was 10.5. All three scoring systems demonstrated excellent discrimination for GC, achieving an AUC of 0.884, 0.89, and 0.876, respectively. In external validation, the AUC values were 0.654, 0.658, and 0.714. Notably, the GC-risk scoring system III exhibited the highest screening efficiency. Urban residents benefited from the effective and verified GC-risk scoring systems, which demonstrated excellent performance in identifying individuals with an elevated risk of GC.

Observed Changes in the Distribution of Colon Cancer Metastasis: A National Cancer Database Review and Institutional Experience.

The University of Louisville has observed a near 70% drop in resectable/borderline resectable metastatic colorectal cancer in the past 5 years. The aim of this study was to evaluate the distribution of colon cancer metastasis at diagnosis and at recurrence. Stage was defined by the American joint committee on cancer (AJCC) eighth edition. Institutional review board approval was granted for post hoc review of stage II and III patients with colon cancer from the University of Louisville prospective hepatic database from 2002 to 2023, as well as for the National cancer database (NCDB) Participant user file (PUF) 2021. The Surveillance epidemiology and end-results (SEER) 22 database was also utilized to corroborate the findings in the NCDB. Between 2018 and 2021 pathological M1a decreased annually (51.9-46.3%), while M1c increased year-over-year (26.6-32.4%) and M1b stayed relatively the same (21.4-21.3%). These differences were significant on chi-squared analysis with a p value of < 0.001. Univariate analysis of the post hoc review between 2017 and 2020 revealed significant differences between stage 4a and 4c in terms of race (p value 0.018), carcinoembryonic antigen (CEA) at diagnosis (p value 0.037), CEA at recurrence (p value 0.012), presence of liver metastasis (p value 0.003), and referral pattern (p value 0.014). Multivariate analysis identified stage 4b as an independent predictor for hepatic metastasis (odds ratio; OR 4.69, p value 0.011). A significant change in the distribution of colon cancer metastases has occurred at an institutional and national level over the past 3-5 years. Interdisciplinary treatment strategies will have to be modified accordingly.

12556 Medullary Thyroid Cancer With Persistent Elevation Of Carcinoembryonic Antigen: Case Report

Abstract Disclosure: M.S. Campana: None. Introduction: Medullary thyroid Cancer (MTC) is a rare neuroendocrine tumor that originates from thyroid parafollicular C-cells and represents 5 % of all thyroid cancers. MTC can be sporadic (75%) or hereditary (25%) associated with multiple endocrine neoplasia type 2 syndrome (MEN2). Serum calcitonin (Ctn) and carcinoembryonic antigen (CEA) are its tumor markers. We report a case of persistently elevated CEA levels despite an undetectable Ctn in a patient with MTC after initial thyroid lobectomy. Description of the case: A 42-year-old woman self-identified a neck lump after intentional weight loss. A neck US showed a right lobe thyroid nodule which resulted as suspicious for malignancy (Bethesda V) with subsequent right lobectomy. Pathology reported a 2.6 cm unexpected MTC with negative surgical margins, extrathyroidal extension, angioinvasion, and lymphatic invasion. No cervical lymph nodes (LNs) were removed. Immunohistochemistry was positive for CEA, chromogranin A, synaptophysin, and Ctn. T2 Nx. One month after lobectomy, the Ctn was 10.5 (0-3.0 pg/mL) and CEA 205.2 (0-3.0 ng/mL Non-smoker; 0-5.0 ng/mL smoker). The patient was then referred to our clinic for further management. Laboratories showed normal serum calcium, PTH, and fractionated plasma metanephrine/normetanephrine. A 2-month post-operative Ctn was undetectable, but CEA was elevated at 24.5. Subsequently, we broaden imaging studies to include neck US, CT neck /chest with contrast, and MRI abdomen pelvis with contrast. The only remarkable finding was a 6.7 cm pelvic mass with normal Ca-125. Genetic testing was negative for germline RET, ruling out MEN2. Patient underwent completion left lobectomy with prophylactic bilateral central neck dissection. Pathology showed benign thyroid parenchyma with multinodular hyperplasia and 0/12 LNs. Because of concerning pelvic mass, the patient was referred to OB/GYN. She underwent a laparoscopic bilateral salpingo-oophorectomy. Pathology showed a follicular ovarian cyst, negative for malignancy. A year post-completion total thyroidectomy Ctn remains undetectable, and a CEA is normal at 1.3. Discussion: Because Ctn was already undetectable 1 month after lobectomy with persistent elevated CEA a complete total thyroidectomy with prophylactic bilateral central neck dissection was indicated to achieve operative cure. Ctn is specific to MTC but variable. CEA is more reproducible with less variability; however, it is not specific to MTC and can also be elevated in smokers, benign breast and genitourinary disease, emphysema, cirrhosis, and cancer of colon, rectum, liver, genitourinary, and lung. If residual disease is present, Ctn tends to be proportionally more elevated than CEA. When the opposite occurs, poorly differentiated MTC with possibility of distant metastases vs. a second primary malignancy vs. a distant benign neoplasm known to elevate CEA need to be ruled out. Presentation: 6/2/2024

6485 Unilateral Adrenal Metastasis From Unknown Primary Carcinoma Mimicking Primary Adrenocortical Carcinoma

Abstract Disclosure: S. Watanabe: None. S. Suzuki: None. K. Ishiwata: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None. Background: Adrenal metastasis from carcinomas of the lung, breast, and melanoma are observed. However, isolated adrenal metastasis with unknown primary carcinoma origin has been rare, and the diagnosis is challenging. We encountered a case of unilateral adrenal tumor clinically diagnosed as non-functional primary adrenocortical carcinoma, but found to be a metastatic tumor on postoperative pathology. Clinical Case: A 68-year-old man was referred to our hospital for examination of an 8mm right adrenal incidentaloma. He underwent hormone therapy for prostate cancer four years ago, and the condition is in remission with no recurrence signs. Follow-up CT revealed that the adrenal tumor rapidly enlarged from 8 mm to 36 mm within six months, and its mean attenuation value was 38 HU. MRI showed that the adrenal tumor had a low signal intensity on T1 and a high signal on T2. At the same time, there is mediastinal lymphadenopathy and a 9-mm nodule in the lower lobe of the right lung, which was considered benign from the stable condition. FDG-PET/CT showed FDG uptake only in the right adrenal tumor (maximum standardized uptake value of 21.39). [1]23I-MIBG scintigraphy did not show any accumulations. The serum and urinary adrenal hormones were all within normal limits. Notably, tumor markers such as prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and cancer antigen 19-9 (CA 19-9) were all within normal ranges. Therefore, we clinically suspected non-functional primary adrenocortical carcinoma, and the laparoscopic right adrenalectomy was performed. The resected right adrenal lesion was encapsulated and measured 79×54×22 mm. On histological analysis, the nodule comprised tumor cells with eosinophilic cytoplasm, and abundant tissue infiltrating lymphocytes. Immunohistochemical studies revealed that the tumor was not of adrenal origin due to negative steroidogenic factor-1 (SF-1) and inhibin alpha staining. From these results, the adrenal tumor was diagnosed as adrenal metastasis from unknown primary carcinoma. The tumor cells were positive for cytokeratin19, CEA, and thyroid transcription factor-1 but negative for PSA, p63, cytokeratin 5/6, insulinoma-associated protein-1, and synaptophysin. Genetically, the adrenal tumor harbored genomic abnormalities in CDKN2A, TP53, NF1, PBRM1, and KEAP1 genes. Conclusion: Isolated adrenal metastasis without a detectable primary tumor is rare but should be considered a differential diagnosis in the case of an enlarged, non-functioning adrenal tumor. Adrenalectomy or tumor biopsy may be actively considered to diagnose and determine the optimal course of treatment. Presentation: 6/3/2024

12396 A Case Of Medullary Thyroid Carcinoma Without Germline RET Mutation

Abstract Disclosure: I. Marranzini Rodriguez: None. M. Lemelman: None. L. Canham: None. Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumor that originates from the parafollicular C cells of the thyroid gland. MTC accounts for approximately 5% of thyroid cancer in children, and the majority of MTC cases are associated with the autosomal dominant tumor predisposition syndrome Multiple Endocrine Neoplasia 2 (MEN2). Sporadic MTC is uncommon in the pediatric population and associated with somatic mutations of RET or RAS (1). Existing management options for metastatic disease have demonstrated some benefit, however, with systemic side effects. Selpercatinib, a highly selective RET kinase inhibitor, is FDA approved for patients &amp;gt;= 12 years of age. Here we present a case of a 10-year-old patient with metastatic MTC with encouraging results. Clinical Case: A previously healthy 10 year 2-month-old male presented with left-sided neck swelling. Imaging showed a 9.7 cm solid mass spanning nearly the entire left neck, occluding the left internal jugular vein, extending to the upper chest, and resulting in high-grade narrowing of the trachea near the thoracic inlet; the mass involved the left thyroid gland and engulfed the left common carotid. His initial lab evaluation showed an elevated TSH of 10.10 mcU/mL (0.6-5.5 mcU/mL) and Free T4 1.22 ng/dL (0.9-1.67 ng/dL). Tumor markers revealed a calcitonin of 32,264 pg/mL (normal range &amp;lt;= 6.0 pg/mL) and carcinoembryonic antigen (CEA) of 200 ng/ml (normal range 0 – 3.4 ng/mL). He underwent biopsy of the mass which showed medullary thyroid carcinoma (MTC) and genetic evaluation of tumoral tissue showed RET c.2753T&amp;gt;C, p.M918T somatic mutation. Evaluation for pheochromocytoma and hyperparathyroidism, given association of MTC with MEN2, was negative. Genetic testing was negative for germline RET mutations. He was started on selpercatinib, 120 mg every 12 hours. Follow up imaging after 2 months of therapy demonstrated a significant decrease in tumor burden. Approximately 5 months after starting he had a decrease in CEA to 14.8 ng/mL and calcitonin to 69 pg/mL, prior to surgery. Given the risk of locoregional recurrence he underwent total thyroidectomy with lateral neck dissection. However, the tumor was noted to be adherent to the trachea, encasing the left recurrent laryngeal nerve, and left carotid artery preventing full resection. He was started on levothyroxine at 62.5 mcg daily on POD#1 and re-started on selpercatinib approximately 2 weeks post-operatively. Conclusion: We present a case of RET-positive metastatic medullary thyroid carcinoma without germline RET mutation successfully treated with selpercatinib. Long-term follow-up for sustained response and tolerability is needed. Reference: 1. Bauer, Andrew J. “Pediatric Thyroid Cancer: Genetics, Therapeutics and Outcome.” Endocrinology and metabolism clinics of North America vol. 49,4 (2020): 589-611. doi:10.1016/j.ecl.2020.08.00 Presentation: 6/2/2024

Development and external validation of a nomogram for predicting lymph node metastasis in 1-3cm lung adenocarcinoma.

Aim: This study aimed to investigate the risk factors for lymph node metastasis in 1-3cm adenocarcinoma and develop a new nomogram to predict the probability of lymph node metastasis.Materials & methods: This study collected clinical data from 1656 patients for risk factor analysis and an additional 500 patients for external validation. The logistic regression analyses were employed for risk factor analysis. The least absolute shrinkage and selection operator regression was used to select variables, and important variables were used to construct the nomogram and an online calculator.Results: The nomogram for predicting lymph node metastasis comprises six variables: tumor size (mediastinal window), consolidation tumor ratio, tumor location, lymphadenopathy, preoperative serum carcinoembryonic antigen level and pathological grade. According to the predicted results, the risk of lymph node metastasis was divided into low-risk group and high-risk group. We confirmed the exceptional clinical efficacy of the model through multiple evaluation methods.Conclusion: The importance of intraoperative frozen section is increasing. We discussed the risk factors for lymph node metastasis and developed a nomogram to predict the probability of lymph node metastasis in 1-3cm adenocarcinomas, which can guide lymph node resection strategies during surgery.

Prognostic insights after surgery for advances in understanding signet ring cell gastric cancer: a machine learning approach

BackgroundSignet ring cell (SRC) gastric carcinoma is traditionally associated with a poor prognosis. However, the literature has presented contradictory results. Linear models are the standard statistical tools typically used to study these conditions. However, machine learning (ML) models have the potential to replace or even outperform linear models in terms of predictive performance. MethodsThis study analyzed 608 patients diagnosed with gastric cancer at our institution. The analysis compared traditional linear models and ML models. Variables examined included demographic data, presence of an SRC component, lymph nodes (LNs) resected and affected (ratio), stage of the disease, body mass index, pathologic features, type of surgery, tumor location, and carcinoembryonic antigen levels to evaluate their influence on 5-year mortality and 2-year recurrence rates. ResultsSRC carcinoma was associated with poorer prognosis in terms of 5-year overall survival than non-SRC carcinoma. In addition, SRC exhibited higher rates of LN metastasis and a higher LN ratio (resected/affected) and was more prevalent in younger patients (<65 years). However, SRC was not an independent factor in the multivariate analysis. Linear models showed worse predictions for 5-year mortality and 2-year recurrence than ML models. The ML models did not consider the presence of the SRC component as an important variable. ConclusionSRC gastric carcinoma continues to present an uncertain prognosis. ML models can evaluate prognosis more accurately than traditional linear models. Large-scale studies using ML algorithms are necessary to elucidate the predictive potential of such models.