Total Number Of Tumors Research Articles

Malignancy risk in diabetes; A population study based on electronic health records

Objective: To document the risk of the most common types of malignancies in people with diabetes compared to the people without diabetes. Methods: The data source of this study is the national electronic health records system of Turkey (e-Nabız). We analysed only the data of people over 14 years old in 2019. All the people with ICD-O-3 codes recorded for the first time in 2019 were accepted as new tumour cases. Tumours with /3 behaviour codes were accepted as malignant. Results: We detected 6,775,054 (10.6%) people with diabetes and 57,167,598 people without diabetes in our database. There were 63,696 new malignant cases in the group with diabetes and 123,662 new malignant cases in the group without diabetes. The total number of malignant tumours was 187,358. All types of major tumours seem to have increased risk. Pancreas cancer has the highest OR (odds ratio), 4.02 (3.71-4.36, 95% confidence interval), and larynx cancer has the lowest OR, 1.29 (1.19-1.41). OR for the presence of any malignancy in a person with diabetes is 1.87 (1.85-1.89). Conclusion: All major types of malignant tumours have an increased incidence in people with diabetes. The results confirm the presence of a relationship between diabetes and malignancy.

Salivary Gland Tumours in Children and Adolescents-A Study in Shaheed Monsur Ali Medical College & Hospital, Uttara, Dhaka, Bangladesh

Introduction: Salivary gland carcinomas (SGCs) are rare neoplasms in adults, but are exceedingly infrequent in children, with a reported annual incidence of 0.8–1.4 per million populations under 20 years old. Like other pediatric very rare tumors, SGCs in children and adolescents often present diagnostic and therapeutic challenges for pathologists, surgeons, and pediatric oncologists. Objective: To assess the salivary gland tumours in children and adolescents. Methods: A cross-sectional observational study was carried out at Dept. of ENT, Shaheed Monsur Ali Medical College & Hospital, Uttara, Dhaka, Bangladesh from January to June 2023. Total 60 patients included in our study. Our pre-operative clinical diagnoses were based on size, shape, mobility, fixity of the tumour to the underlying structures, ulceration of overlying skin, involvement of facial nerve by its malignant transformation and fine needle aspiration cytology. All patients, or their guardians, gave their informed consent for data collection within the national rare tumour group and analysis. Results: Total sixty (60) cases of salivary gland tumours were available for our study. Out of 55% were male and 45% were female patients. Incidence of tumours is highest in the age group of 41-50 with 13 cases (21.6% of the total). The least affected age group was the 0-10 group with only one patient (3.3%). Women accounted for 16 cases of the total 33 benign neoplasias (55% of the total). Of the 33 benign tumour, 18 were in males (54.5% of all benign tumours) and 15 were in females (45.5%). Total 60 operated cases). Of these, 32 were pleomorphic adenomas (53.3%) and 1 was an adenolymphoma (1.6%). the total number of malignant tumours confirmed by HPE were 27 (45%). Of these, most numerous was adenoid cystic carcinoma in 8 cases (13.3%). squamous cell carcinoma and muco epidermoid carcinoma were found in 6 cases each (10%). There were 4 and 3 cases of adenocarcinoma (6.6%) and acinic cell carcinoma (5%) respectively. The parotid glands were also the sole location for the 3 acinic cell carcinomas. No tumours were found in the sublingual gland. The majority of the tumours found in the parotid gland were benign tumours, mainly pleomorphic adenomas with 24 cases (75% of the total parotid tumours). Conclusions: The tumours were equally distributed between males and females. The tumours were most commonly found in the third to fifth decades of life. The most common benign tumour and the most common tumour overall was pleomorphic adenoma making up 54.5% of all tumours. Surgical excision was the most commonly done treatment. The most commonly done surgical procedure was superficial parotidectomy.

8080 Factors Affecting Survival of Lymph Node Positive Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program

Abstract Disclosure: M. Mortagy: None. A. Abdelhameed: None. M. Hegazy: None. Introduction: 50-70% of patients with MTC have positive lymph nodes. The Aim is to identify factors affecting survival of the lymph node positive MTC sub-population. Understanding these factors is important in treating these patients. Methods 1359 patients with lymph node positive MTC who were diagnosed with positive histology or cytology from 1975 to 2020 were extracted from SEER after removing duplicates. Survival analysis was performed, and Kaplan-Meier graph was produced. Univariate and multivariable Cox regression were performed, and respective hazard ratios (HR) were generated. Results: The cohort were 54% males with a median age of 55 years. Median survival: for the cohort was 163 months with survival of 91%, 80% and 74% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.04), female sex (HR 0.64), T4 stage (HR 2.48), M1 stage (HR 5.43), bone metastasis (HR 4.74), brain metastasis (HR 17.1), liver metastasis (HR 5.41), lung metastasis (HR 5.97), distant lymph node metastasis (HR 6.00), number of positive lymph nodes (HR 1.008), lymph node ratio (HR 4.50), tumor size (HR 1.02), multifocal tumor (HR 0.69), total number of malignant tumors (HR 1.21), not performing total thyroidectomy (HR 6.35), chemotherapy (HR 3.85), radiotherapy after surgery (HR 1.67), beam radiotherapy (HR 2.20), systemic therapy after surgery (HR 0.67). Univariate Cox regression was not statistically significant for grade, treatment delay, total number of benign tumors, race/ethnicity, income, and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for number of positive lymph nodes (HR 1.03), bone metastasis (HR 0.18), liver metastasis (HR 14.57), multifocal tumor (HR 3.49), total number of malignant tumors (HR 2.66), T4 stage (HR 3.57), M1 stage (HR 3.65), not performing total thyroidectomy (HR 352.43), tumor size (HR 1.03). Conclusion: Number of positive lymph nodes, T4 stage, M1 stage, presence of liver metastasis, presence of multifocal tumor, not performing total thyroidectomy and large tumor size lead to worse prognosis. Age, gender, chemotherapy, and lymph node ratio don’t affect survival. Future research is required to study this group of patients. Presentation: 6/2/2024

8061 Factors Affecting Survival of Metastatic Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program

Abstract Disclosure: A. Abdelhameed: None. H. Ibrahim: None. M. Mortagy: None. Introduction: Medullary thyroid cancer (MTC) arises from parafollicular cells of the thyroid. 43% of patients with MTC have metastasis. It was shown that the overall 5-year survival of patients with MTC is 40.4%. The clinical course of MTC is highly variable. The Aim is to identify factors affecting survival of the metastatic MTC sub-population. Understanding these factors is important in treating these patients. Methods 340 patients: with metastatic MTC who were diagnosed from 1975 to 2020 were extracted from SEER after removing duplicates and those not diagnosed by positive histology or cytology. Survival analysis was conducted, and Kaplan-Meier graph was generated. Univariate Cox regression was performed for all variables and respective hazard ratios (HR) were produced. Multivariable cox regression was performed for statistically significant variables. Results: The cohort were 59% males with a median age of 60 years. Median survival for the cohort was 20 months with survival of 63%, 41% and 31% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.02), brain metastasis (HR 2.70), liver metastasis (1.65), lung metastasis (1.42), not performing total thyroidectomy (HR 2.77), lymph node ratio (HR 2.45), and systemic therapy after surgery (HR 0.34). Univariate Cox regression was not statistically significant for sex, grade, radiotherapy, chemotherapy, treatment delay, bone metastasis, distant lymph node metastasis, multifocal cancer, total number of benign and malignant tumors, race/ethnicity, income, tumor size and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for age (HR 1.04), presence of lung metastasis (HR 1.91), and systemic therapy before surgery (HR 14.41). Conclusion: Increasing age, presence of lung metastasis and systemic therapy before surgery lead to worse prognosis in metastatic MTC. Gender, grade, radiotherapy, chemotherapy, treatment delay, bone or brain or liver metastasis, presence of multifocal cancer, race, tumor size and surgery don't affect survival according to multivariable cox regression. Future research is needed to study this group of patients. Presentation: 6/2/2024

Personalized approach to malignant struma ovarii: Insights from a web-based machine learning tool.

Malignant struma ovarii (MSO) is a rare ovarian tumor characterized by mature thyroid tissue. The diverse symptoms and uncommon nature of MSO can create difficulties in its diagnosis and treatment. This study aimed to analyze data and use machine learning methods to understand the prognostic factors and potential management strategies for MSO. In this retrospective cohort, the Surveillance, Epidemiology, and End Results (SEER) database provided the data used for this study's analysis. To identify the prognostic variables, we conducted Cox regression analysis and constructed prognostic models using five machine learning algorithms to predict the 5-year survival. A validation method incorporating the area under the curve of the receiver operating characteristic curve was used to validate the accuracy and reliability of the machine learning models. We also investigated the role of multiple therapeutic options using the Kaplan-Meier survival analysis. The study population comprised 329 patients. Multivariate Cox regression analysis revealed that older age, unmarried status, chemotherapy, and the total number of tumors in patients were poor prognostic factors. Machine learning models revealed that the multilayer perceptron accurately predicted outcomes, followed by the random forest classifier, gradient boosting classifier, K-nearest neighbors, and logistic regression models. The factors that contributed the most were age, marital status, and the total number of tumors in the patients. The present study offers a comprehensive approach for the treatment and prognosis assessment of patients with MSO. The machine learning models we have developed serve as a practical, personalized tool to aid in clinical decision-making processes.

Uveal melanoma distant metastasis prediction system: A retrospective observational study based on machine learning.

Uveal melanoma (UM) patients face a significant risk of distant metastasis, closely tied to a poor prognosis. Despite this, there is a dearth of research utilizing big data to predict UM distant metastasis. This study leveraged machine learning methods on the Surveillance, Epidemiology, and End Results (SEER) database to forecast the risk probability of distant metastasis. Therefore, the information on UM patients from the SEER database (2000-2020) was split into a 7:3 ratio training set and an internal test set based on distant metastasis presence. Univariate and multivariate logistic regression analyses assessed distant metastasis risk factors. Six machine learning methods constructed a predictive model post-feature variable selection. The model evaluation identified the multilayer perceptron (MLP) as optimal. Shapley additive explanations (SHAP) interpreted the chosen model. A web-based calculator personalized risk probabilities for UM patients. The results show that nine feature variables contributed to the machine learning model. The MLP model demonstrated superior predictive accuracy (Precision = 0.788; ROC AUC = 0.876; PR AUC = 0.788). Grade recode, age, primary site, time from diagnosis to treatment initiation, and total number of malignant tumors were identified as distant metastasis risk factors. Diagnostic method, laterality, rural-urban continuum code, and radiation recode emerged as protective factors. The developed web calculator utilizes the MLP model for personalized risk assessments. In conclusion, the MLP machine learning model emerges as the optimal tool for predicting distant metastasis in UM patients. This model facilitates personalized risk assessments, empowering early and tailored treatment strategies.

Characterization of skin tumors in an Egyptian large tertiary center

Skin tumors are a global health problem caused by UV exposure with ethnic and geographical distribution. This research summarized Egyptian skin tumor features. A cross-sectional study was conducted in the Al-Hussein Teaching Hospital, Al-Azhar University, Cairo, Egypt. Patients’ data were collected from the hospital-recorded registry from January 2010 to December 2020. Results: The age group, 19-59y, showed the highest prevalence, 57% (n=940), of skin tumors. The total number of skin tumor patients was 1649 (males 52.9% (n=872), females 47.1% (n=777). For benign skin tumors, the male-to-female ratio was 1: 0.96, and for malignant skin tumors, the male-to-female ratio was 1: 1.47. The frequency of skin tumors at the sun-exposed site (out of the total n= 1770) was 39.4% (n= 697) and the face showed the highest frequency 25.8% (n=457). The frequency of skin tumors at the non-sun-exposed sites was 60.6% (n=1073) of the total skin tumor number. Basal cell carcinoma (BCC) showed a frequency of 90.1% of cases affecting sun-exposed sites. Therefore, skin tumors have unique characteristics in Egypt, with malignant skin tumors being rare showing more predilection in males. Further studies are needed to emphasize the national characteristics of skin tumors in Egypt.

Effect of tumor burden on survival in patients with stage IV EGFR-mutant NSCLC receiving osimertinib monotherapy.

8611 Background: Osimertinib (osi) has traditionally been given as monotherapy for patients (pts) with stage IV EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), although acquired resistance remains a challenge. Recent data from the FLAURA2 study demonstrated a progression free survival (PFS) benefit of approximately 9 months (mos) when osi is combined with platinum-pemetrexed chemotherapy. Despite this improvement, combination therapy is associated with higher rates of adverse events, making it challenging to decide which pts should receive TKI + chemo vs TKI monotherapy. Tumor burden (TB) in pts with stage IV EGFRm NSCLC, which may be associated with risk of developing resistant clones on TKI monotherapy, and its association with clinical outcomes has not been examined. Methods: Retrospective, single institution manual case review of pts who received osi monotherapy. Primary objectives were PFS (i.e., oligoprogression requiring local therapy, disease progression (PD) with osi discontinuation, or death) and overall survival (OS) related to extent of TB. Those who did not receive osi monotherapy for stage IV EGFRm NSCLC or discontinued osi for reasons other than PD were excluded. Demographics, comorbidities, performance status, PD-L1 expression, histology, EGFRm subtype, prior TKI use, total number of visceral tumors (TTn), and total number/sites of metastatic disease (MDn) collected for analysis. Extent of TB categorized by TTn (1-4, 5-9, ≥10) and MDn (1-2, 3-4, ≥5). PFS and OS estimated by Kaplan-Meier method and compared using log-rank test. Results: 325 pts eligible for analysis. Median follow-up time was 22.7 mos. Median PFS (mPFS) for the overall cohort was 16.3 mos (95% CI; 13.7 - 18.9) and median OS (mOS) was 31.1 mos (95% CI; 27.4 - 39.3). Pts with a TTn of 1-4 had significantly better mPFS compared to those with a TTn of 5-9 and ≥10 (mPFS: 21.5 vs 16.3 vs 13.4 mos, respectively; P = 0.001). Pts with a TTn ≥10 had significantly worse mOS compared to those with a TTn of 5-9 and 1-4 (23.7 vs 35.1 vs 57.7 mos, respectively; P < 0.0001). Similarly, pts with a MDn of 1-2 had significantly better mPFS and mOS compared to those with a MDn of 3-4 and ≥5 (mPFS: 21.6 vs 11.4 vs 9.0 mos, respectively [P < 0.0001]; mOS: 44.3 vs 20.8 vs 22.4, respectively [P < 0.0001]). Pts with liver and bone mets had significantly worse mPFS and mOS, whereas those with lung and brain mets had worse mOS without affecting PFS. Conclusions: The extent of baseline TB, categorized by TTn and MDn, impacts both PFS and OS in pts with stage IV EGFRm NSCLC treated with osi monotherapy. Pts with “low-TB” (i.e., TTn 1-4, MDn 1-2) appear to have a survival advantage compared to those with “intermediate- or high-TB” (i.e., TTn 5-9 and ≥10, MDn 3-4 and ≥5) and may derive less benefit from the addition of chemotherapy to osi. Prospective, matched real-world treatment cohorts are warranted to optimize treatment strategies for this patient population.

Unusual localization of a digital neurofibroma: About a case and review of the literature

Neurofibromas are benign tumors of peri-nervous origin. may occur as a single lesion (solitary neurofibroma) or as part of a neurofibromatosis type 1. We present a case of a 44-year-old man with a painful neurofibroma on the dorsal surface of the 3rd right finger, revealed by a painful mass on its posterolateral aspect. Treatment was by excisional biopsy, with histopathological examination confirming the diagnosis. In the study by Lincoski et al, 24 benign nerve tumours accounted for 11.5% of the total number of soft-tissue tumours in the hand and forearm. Isolated neurofibromas are rare in the hand and normally grow slowly over many years. MRI provides precise information on the anatomical relationships of the tumour. Even with a correct diagnosis, the therapeutic decision must be carefully considered.

PACULIARITIES OF CLINICAL PRESENTATION, DIAGNOSIS, AND TREATMENT FOR INJURIES OF THE LARGE SALIVARY GLANDS

Background. Salivary gland lesions of various genesis are quite widespread among patients, tumorous processes involving these organs make up 2.2-3.7% of the total number of head and neck tumors, 78-82% of salivary gland tumor cases, and sialoadenitis, which makes 3.8-6.7% of the total number of inflammatory diseases of maxillofacial organs. The initial diagnostic imaging for parotid gland tumors typically involves an ultrasound examination; however, it does not definitively indicate the need for surgical intervention. While computed tomography or magnetic resonance imaging are not obligatory elements of patient assessment, they may be recommended in specific instances to facilitate accurate treatment planning.
 Fine-needle aspiration biopsy can serve as an obligatory diagnostic test, irrespective of whether an ultrasound examination has been conducted, particularly when there are suspicions of atypical presentations of polymorphic adenoma. Incisional biopsy is contraindicated, as it frequently leads to neoplastic implantation, thereby increasing the risk of recurrence of polymorphic adenomas and malignant neoplasms.
 The purpose of the study is to conduct a comparative analysis of the data of clinical examinations, laboratory tests, surgical treatment, complications and postoperative results, taking into account the prevalence of tumor and inflammatory processes of the parotid salivary glands.
 Material and methods. We have conducted a retrospective study of the medical histories of 174 patients operated on at the Department of Maxillofacial Surgery of the “Poltava Regional Clinical Hospital named after M.V. Sklifosovsky”.
 Results. According to our data, pleomorphic adenoma was the most common benign tumor, and mucoepidermoid carcinoma was the most frequently detected malignant tumor. Regarding initial presentations, the primary observation was a tumor mass in 96.1% of all cases. Additional findings included incidental lesions detected during imaging studies and localized pain or inflammation. Isolated occurrences of inadvertent lesions during imaging of neoplasms have also been documented. Palpation was recognized as an excellent clinical parameter for topographic localization and classification of lesions for malignancy, with proven value in the specimen due to its high sensitivity for demonstrating nodules in the superficial lobe (97.1%) and high specificity for nodules in the deep lobe. We established that the average evolution time of benign tumors was approximately three times longer than that of malignant tumors. These data are consistent with literature data that malignant tumors are more aggressive and have a rapid evolution, while benign, in turn, have an insidious onset and slow growth. During intraoperative examination, high specificity is desirable because it can reliably exclude malignancy, preventing unnecessary radical interventions. Another intervention that we have analyzed in the treatment of benign tumors is dermal parotidectomy, which showed a recurrence rate similar to superficial parotidectomy, although with a lower rate of serious complications (12.4% less on average). It has been found that the choice of this intervention is mainly related to the incidence of recurrence, and in 51-56% of cases in patients with a previous fine-needle aspiration biopsy.
 Conclusion. According to this study, taking into account the experience of our clinic, the presence and visualization of a single nodule in the parotid area is the main clinical manifestation of parotid gland cancer. Pleomorphic adenoma is the most common histological type, and facial nerve-sparing subtotal parotidectomy is the best treatment for these patients.

Prediction of all-cause death and specific causes of death in patients with gastric cancer with liver metastasis: a Surveillance, Epidemiology, and End Results–based study

BackgroundGastric cancer (GC), considered the fifth most prevalent malignancy, is the fourth leading cause of cancer death worldwide. This cancer is heterogeneous and invasive and often metastasizes to the liver. The survival of patients with GC, especially cancer-specific survival (CSS), is a matter of concern to their families and medical workers in clinical practice. However, efficient tools for early risk prediction are lacking. Thus, this study aimed to develop a nomogram for forecasting the overall survival (OS) and CSS of patients with GC with liver metastasis (GCLM) based on the Surveillance, Epidemiology, and End Results (SEER) database. MethodsInformation on individuals with GCLM was acquired from the SEER database from January 2000 to December 2015. Patients’ data were randomized into the train cohort and the test cohort. The independent factors for CSS and OS were determined by univariate and multivariate competing risk analyses and Cox proportional hazards analysis, and the nomograms for predicting CSS and OS were constructed. The receiver operating characteristic curve and calibration curve were used to measure the accuracy and calibration of nomograms. ResultsOur study included 4372 patients with GCLM, with 3060 patients in the train set and 1312 in the test set. The mean follow-up period was 12.31 months. The independent factors influencing the OS of patients with GCLM were age, bone metastasis, chemotherapy, grade, lung metastasis, stage, primary site, radiotherapy, surgical primary site, T stage, and tumor size. The concordance Index (C-index) of the constructed nomogram for OS were 0.718 (SE, 0.004) in the train set and 0.0.680 (SE, 0.006) in the test set. The independent factors affecting the CSS of patients with GCLM were age, chemotherapy, grade, lung metastasis, stage, radiotherapy, regional lymph node positive, surgical primary site, and total number of tumors. The C-index for the constructed nomogram for CSS were 0.696 (SE, 0.005) in the train set and 0.696 (SE, 0.008) in the test set. ConclusionThe constructed nomograms showed satisfactory performance in predicting the OS and CSS of patients with GCLM, which can help clinicians formulate follow-up and rehabilitation strategies conducive to survival. At the same time, it can provide more family and social support for high-risk groups.

New gold(III) complexes TGS 121, 404, and 702 show anti-tumor activity in colitis-induced colorectal cancer: an in vitro and in vivo study

BackgroundChronic inflammation in the course of inflammatory bowel disease may result in colon cancer, or colitis-associated colorectal cancer (CACRC). It is well established that CACRC is associated with oxidative stress and secretion of multiple pro-inflammatory cytokines, e.g. tumor necrosis factor-α. Recently, we proved that the administration of gold(III) complexes resulted in the alleviation of acute colitis in mice. The aim of the current study was to assess the antitumor effect of a novel series of gold(III) complexes: TGS 121, 404, 512, 701, 702, and 703.MaterialsAnalyzed gold(III) complexes were screened in the in vitro studies using colorectal cancer and normal colon epithelium cell lines, SW480, HT-29, and CCD 841 CoN, and in vivo, in the CACRC mouse model.ResultsOf all tested complexes, TGS 121, 404, and 702 exhibited the strongest anti-tumor effect in in vitro viability assay of colon cancer cell lines and in in vivo CACRC model, in which these complexes decreased the total number of colonic tumors and macroscopic score. We also evidenced that the mechanism of action was linked to the enzymatic antioxidant system and inflammatory cytokines.ConclusionsTGS 121, 404, and 702 present anti-tumor potential and are an attractive therapeutic option for colorectal cancer.

Abstract B039: Effect of cross-sex testosterone therapy on Pik3ca-driven breast cancer incidence in mice

Abstract Background: The majority of transmasculine individuals—assigned female at birth—pursue gender-affirming testosterone therapy (TT) to treat their gender dysphoria. It remains unknown the extent to which TT modulates the breast, including breast cancer (BC) risk, in transmasculine individuals. Given that hormone regulation of breast development is similar in mice and humans, mouse models are an excellent methodology to understand the effect of TT on BC development. We used a BC mouse model, MMTV-Cre Pik3caf/wt, to investigate the effect of testosterone on estrogen receptor positive (ER+) BC development. Method: Immunohistochemistry confirmed that our MMTV-Cre Pik3caf/wt tumors are ER+. We established 5 study arms: female controls (n=4), oophorectomized female controls (n=6), male mice (n=5), female mice receiving weekly 400 µg s.c. of testosterone cypionate (n=5), and oophorectomized female mice receiving weekly testosterone cypionate (n=5). Mammary tumor development was monitored weekly; palpable tumors were measured 3x a week. Mice were euthanized when their largest tumor reached 1cm, or if multiple tumors arise, when the combined tumor burden reaches 2 cm. Mice that have not reached endpoint by 48 weeks of age were euthanized and censored. The total number of tumors were observed during necropsy. Results: All 4 female controls developed a mean of 4 tumors each and were euthanized at around 35 weeks as the largest tumor reached 1 cm. The remaining mice were euthanized study endpoint of 48 weeks. Only 1 of 5 female mice receiving testosterone had a macroscopic tumor at 48 weeks. Hence, the total number of tumors developed among female mice receiving testosterone are similar or lower than female controls. Three out of 6 of oophorectomized females developed an average of 2 tumors while 2 of 5 female oophorectomized mice receiving testosterone developed 3 tumors each. Thus, when compared to intact females, oophorectomy appears to increase the lag time to Pik3ca tumor development. Lastly, 1 of 5 male mice developed 4 tumors. Conclusion: This pilot study demonstrated that testosterone does not increase ER+ BC incidence in Pik3ca-transgenic mice. Findings in oophorectomized mice suggest that aromatization of testosterone to estradiol may not contribute significantly to tumor development in these mice. Our findings provides insights into about BC risk associated with TT in transmasculine individuals. More studies are warranted to understand the health effects of gender-affirming hormone therapy, and reduce healthcare disparities in the transgender community. Citation Format: Lin Wang, Abhishek Thavamani, Erica S. Massicott, Vanessa C. Bret-Mounet, Joseph Abirached, John G. Clohessy, Gabrielle M. Baker, Gerburg M. Wulf, Yujing Jan Heng. Effect of cross-sex testosterone therapy on Pik3ca-driven breast cancer incidence in mice [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B039.

Analysis of prognostic factors in patients diagnosed with bladder cancer complicated by hemorrhage treated by drug-eluting bead embolization.

Transcatheter bladder arterial chemoembolization (TACE) is an alternative treatment used to control bladder cancer (BC) with bleeding, especially in older adult patients with comorbidities. This retrospective observational study evaluated the effect and prognostic factors of transcatheter drug-eluting bead (DEB) embolization in patients with advanced BC. We assessed 39 patients diagnosed with BC with hemorrhage who were either inoperable or unwilling to undergo surgery at our hospital between January 2018 and October 2022. All patients underwent TACE by DEB loaded with epirubicin and imaging scans after 2 months to evaluate the curative effect according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) standard to determine treatment. Re-examination and follow-up were performed every 3-6 months to observe hematuria recurrence and the curative effect. A total of 95 interventional treatments were performed in 39 patients, and all participants achieved complete hemostasis within 5 days after the first intervention. Computed tomography or magnetic resonance imaging showed that the total effective rate [complete response (CR) + partial response (PR)] was 64.1%, and the disease benefit rate (CR +PR + stable disease) was 79.5%. A total of 30 patients (76.9%) had no hematuria recurrence. Logistic regression analysis indicated that the type of blood supply in BC may relate to whether the patients benefited from the intervention. Hematuria recurrence was significantly associated with the total number of tumors and the type of blood supply (P<0.05). Superselective embolization of bladder arteries with DEB can be used to treat BC with hemorrhage. However, hypovascular tumor blood supply may result in poor postoperative efficacy and hematuria recurrence. Additionally, multiple bladder tumors may be a risk factor for hematuria recurrence.

The association between NRF2 transcriptional gene dysregulation and IDH mutation in Grade 4 astrocytoma

Abstract Objectives Nuclear factor erythroid-2-related factor 2 (NRF2), a transcriptional gene factor related to nuclear factor erythroid 2, plays a role in the development of gliomas with isocitrate dehydrogenase (IDH) mutation. Its impact on tumour recurrence has seldom been investigated. Methods A group of 34 patients diagnosed with Grade 4 astrocytoma was included in a retrospective cohort. NRF2 protein and gene expressions were assessed using different profiling assays. The association between IDH mutation, NRF2 expression, and tumor recurrence was investigated. Results The mean patients’ age in this study was 50 years. Out of the total number of tumors analyzed, 21 of them had IDH mutation. NRF2 protein expression was found to be overexpressed in 27 tumors and reduced in 7 tumors. Additionally, NRF2 gene was upregulated in 24 tumors and downregulated in 10 tumors. Insignificant statistical difference was observed in recurrence-free interval (RFI) between patients with upregulated or downregulated NRF2 gene or protein expressions (p-value&gt;0.05). However, this relationship is distinctive when NRF2 expression was compared to IDH mutation. Tumors with different levels of NRF2 expressions and IDH mutations showed significant statistical variation in RFI (p-value=0.001). There was insignificant impact on RFI among patients receiving different chemotherapies (TMZ or TMZ plus) who had abnormal NRF2 gene activities (p-value=0.97). Conclusions WHO-Grade 4 astrocytoma with IDH mutation and altered NRF2 expression showed a delayed tumor recurrence compared to IDH-wildtype glioblastoma.

6-Shogaol prevents benzo (A) pyrene-exposed lung carcinogenesis via modulating PRDX1-associated oxidative stress, inflammation, and proliferation in mouse models.

In this study, we have investigated the chemopreventive role of 6-shogaol (6-SGL) on benzopyrene (BaP) exposed lung carcinogenesis by modulating PRDX1-associated oxidative stress, inflammation, and proliferation in Swiss albino mouse models. Mice were exposed to BaP (50 mg/kg b.wt) orally twice a week for four consecutive weeks and maintained for 16 weeks, respectively. 6-SGL (30 mg/kg b.wt) were orally administered to mouse 1 h before BaP exposure for 16 weeks. After the experiment's termination, 6-SGL (30 mg/kg b.wt) prevented the loss in body weight, increased lung weight, and the total number of tumors in the mice. Moreover, we observed that 6-SGL treatment reverted the activity of BaP-induced lipid peroxidation and antioxidants in mice. Also, 6-SGL impeded the phosphorylation of MAPK family proteins such as Erk1, p38, and Jnk1 in BaP-exposed mice. PRDX1 is an essential antioxidant protein that scavenges toxic radicals and enhances several antioxidant proteins. Overexpression of PRDX1 substantially inhibits MAPKs, proliferation, and inflammation signaling axis. Hence, PRDX1 is thought to be a novel targeting protein for preventing BaP-induced lung cancer. In this study, we have obtained the 6-SGL treatment in a mouse model that reverted BaP-induced depletion of PRDX1 expression. Moreover, pretreatment of 6-SGL (30 mg/kg b.wt) significantly inhibited enhanced proinflammatory cytokines (TNF-α, IL-6, IL-β1, IL-10) and proliferative markers (Cyclin-D1, Cyclin-D2, and PCNA) in BaP-exposed mice. The histopathological studies also confirmed that 6-SGL effectively protected the cells with less damage. Thus, the study demonstrated that 6-SGL could be a potential phytochemical and act as a chemopreventive agent in BaP-induced lung cancer by enhancing PRDX1 expression.

In-vivo anticancer activity of biosynthetic silver nanoparticles of Cassia marginata Roxb against NMU-Induced mammary carcinoma

The use of silver nanoparticles in the diagnosis and treatment of cancer is on the rise, and they are becoming more commonly recognized as effective therapeutic agents. Silver nanoparticles of Cassia marginata Roxb were prepared to investigate its anticancer potential in female Sprague-Dawley rats against N-nitroso N-methyl urea-induced mammary carcinoma. In this study, thirty animals were divided into five groups of six each: normal, disease control, Cassia marginata silver nanoparticles at 200 mg/kg, 400 mg/kg, and tamoxifen 10 mg/kg. N-nitroso N-methyl urea (50 mg/kg, i.p) was given twice at 52 days of age and four weeks after the prior treatment in 0.9 % NaCl. A total of two oral doses of Cassia marginata silver nanoparticles were administered, and the results were compared to the results of a single dose of tamoxifen (10 mg/kg, p.o). The tumor incidence rate, average tumor burden, and the total number of tumors were reduced in the treatment groups when compared with the disease control and the silver nanoparticles of Cassia marginata may prevent mammary carcinoma in Sprague-Dawley rats when exposed to N-nitroso N-methyl urea.

DS26 Review of 2-week suspected skin cancer activity shows a large increase in number of patients with basal cell carcinoma: implications for designing services and workforce planning

Abstract The 2-week wait (2WW) suspected skin cancer referral pathway is for people with high-risk skin cancers in particular squamous cell carcinoma (SCC) and malignant melanoma (MM) but not for most basal cell carcinomas (BCC). Conversion rates reflecting the number of SCC and MM diagnosed via a 2WW pathway are around 8–12%. Prior to the COVID-19, pandemic people with straightforward low-risk BCCs would be referred on a routine pathway with an expectation that their management would be completed within 18 weeks. The postpandemic pressure on routine waiting lists has meant that managing patients with BCC in a timely fashion is challenging, and the impression is that these patients are now being referred on the 2WW pathway to avoid delays in treatment. The aim of this study was to review the 2WW referral activity between 2019 and 2022, particularly in relation to the number of patients with BCC. Data were obtained from the cancer team (Table 1). There has been a 68% increase in 2WW referral activity. The proportion of people discharged at first attendance and the MM and SCC conversion rate has remained fairly stable. Looking specifically at BCCs, there was an increase from 13.7% to 16.2%. The total number of tumours managed increased overall by 85% over the study period (Table 1). For BCC, the activity has doubled from 552 to 1108 patients (to the end of November 2022). These data confirm the large increase in the number of patients referred on the 2WW suspected skin cancer pathway. Although there is little change in the proportion of patients with different types of skin cancer being seen and managed, the total numbers reported here demonstrate a significant knock-on impact of additional workload for specialist teams, including the need for more skin surgery activity, histopathology and specialist skin cancer nursing services. This needs to be considered when developing skin lesion diagnostic and management pathways and confirms the importance of developing locally agreed BCC pathways and defining workforce requirements.Table 1Two-week wait (2WW) referral activity between 2019 and 2022Number of tumours managed2019202020212022 (to the end of November 2022)2WW referrals (n)4038480260636837Discharged at first attendance (%)56505454Melanoma (%)2.32.221.8SCC (%)5.98.47.65.8Conversion rate (SCC and MM) (%)8.210.69.69.6BCC (%)13.713.816.516.2Number of tumoursSCC237403461395Melanoma93104121124BCC5526629981108Total882116915801627

Allyl isothiocyanate inhibits invasion and angiogenesis in breast cancer via EGFR-mediated JAK-1/STAT-3 signaling pathway.

Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK-1/STAT-3 is a key intracellular signaling transduction pathway, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis of various cancer cells. The present study explored the impact of allyl isothiocyanate (AITC) on the JAK-1/STAT-3 pathway in DMBA-induced rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25mg DMBA/rat by a subcutaneous injection administered near the mammary gland. We observed decreased body weight and increased the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-induced rats that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBA-induced rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, nuclear fraction of STAT-3, VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic fraction of STAT-3 and TIMP-2. Oral administration of AITC on DMBA-induced rats inhibits angiogenesis and invasion by modifying these angiogenic and invasive markers. The finding of the present study was further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT-3 glide energy of -18.123 and -72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 pathway, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.

Zearalenone attenuates colitis associated colorectal tumorigenesis through Ras/Raf/ERK pathway suppression and SCFA-producing bacteria promotion

The high prevalence of colorectal cancer (CRC) and its leading death causing rate have placed a considerable burden on patients and healthcare providers. There is a need for a therapy that has fewer adverse effects and greater efficiency. Zearalenone (ZEA), an estrogenic mycotoxin, has been demonstrated to exert apoptotic properties when administrated in higher doses. However, it is unclear whether such apoptotic effect remains valid in an in vivo setting. The current study aimed to investigate the effect of ZEA on CRC and its underlying mechanisms in the azoxymethane/ dextran sodium sulfate (AOM/DSS) model. Our results revealed that ZEA significantly lowered the total number of tumours, colon weight, colonic crypt depth, collagen fibrosis and spleen weight. ZEA suppressed Ras/Raf/ERK/cyclin D1 pathway, increasing the expression of apoptosis parker, cleaved caspase 3, while decreasing the expression of proliferative marker, Ki67 and cyclin D1. The gut microbiota composition in ZEA group showed higher stability and lower vulnerability in the microbial community when compared to AOM/DSS group. ZEA increased the abundance of short chain fatty acids (SCFAs) producing bacteria unidentified Ruminococcaceae, Parabacteroidies and Blautia, as well as the faecal acetate content. Notably, unidentified Ruminococcaceae and Parabacteroidies were substantially correlated with the decrease in tumour count. Overall, ZEA demonstrated a promising inhibitory effect on colorectal tumorigenesis and exhibited the potential for further development as a CRC treatment.