Staging Of Adenocarcinoma Research Articles

Differential cellular communication in tumor immune microenvironment during early and advanced stages of lung adenocarcinoma.

Heterogeneous behavior of each cell type and their cross-talks in tumor immune microenvironment (TIME) refers to tumor immunological heterogeneity that emerges during tumor progression and represents formidable challenges for effective anti-tumor immune response and promotes drug resistance. To comprehensively elucidate the heterogeneous behavior of individual cell types and their interactions across different stages of tumor development at system level, a computational framework was devised that integrates cell specific data from single-cell RNASeq into networks illustrating interactions among signaling and metabolic response genes within and between cells in TIME. This study identified stage specific novel markers which remodel the cross-talks, thereby facilitating immune stimulation. Particularly, multicellular knockout of metabolic gene APOE (Apolipoprotein E in mast cell, myeloid cell and fibroblast) combined with signaling gene CAV1 (Caveolin1 in endothelial and epithelial cells) resulted in the activation of T-cell mediated signaling pathways. Additionally, this knockout also initiated intervention of cytotoxic gene regulations during tumor immune cell interactions at the early stage of Lung Adenocarcinoma (LUAD). Furthermore, a unique interaction motif from multiple cells emerged significant in regulating the overall immune response at the advanced stage of LUAD. Most significantly, FCER1G (Fc Fragment of IgE Receptor Ig) was identified as the common regulator in activating the anti-tumor immune response at both stages. Predicted markers exhibited significant association with patient overall survival in patient specific dataset. This study uncovers the significance of signaling and metabolic interplay within TIME and discovers important targets to enhance anti-tumor immune response at each stage of tumor development.

Esophageal cancer: new developments in prevention and therapy

Esophageal carcinomas comprise 2 entities, squamous cell carcinoma and adenocarcinoma, which differ in pathogenesis and treatment. Elimination of inflammatory influences and risk factors, such as obesity and gastroesophageal reflux that contribute to a rising incidence of adenocarcinoma, is crucial for tumor prevention. In Germany, general endoscopic screening for upper GI tumors is not recommended, whereas endoscopic surveillance is applied in the presence of Barrett's metaplasia. In the future, better prediction models will be needed to identify patients at risk who will benefit from endoscopic surveillance. Precancerous lesions and early tumor stages can be removed endoscopically using modern resection methods. In recent years, therapeutic strategies for advanced esophageal tumors have undergone significant changes. In the multimodal treatment of locally advanced stages, radiochemotherapy remains to play a key role for squamous cell carcinoma, whereas new evidence highlights the importance of perioperative chemotherapy for the optimal management of adenocarcinoma. Systemic treatment options for both tumor entities have been significantly expanded due to the successful use of immune checkpoint inhibitors in adjuvant and palliative treatment regimen. Determination of PD-L1 and MSI status has therefore become decisive for the choice of therapy. In metastatic stages of adenocarcinoma, chemotherapy can now be supplemented by multiple antibodies directed against Her2, PD1, or claudin 18.2, and the antibody-drug conjugate trastuzumab deruxtecan has become a Her2-targeted option in second line treatment.

Application of 18F-fluorodeoxyglucose PET/computed tomography in the diagnosis of infiltrative subsolid nodules in lung adenocarcinoma

Purpose To investigate the diagnostic value of 18F-fluorodeoxyglucose(FDG) PET/computed tomography (CT) for infiltrative subsolid nodules at different stages of lung adenocarcinoma and to explore predictive factors for invasive adenocarcinoma, providing compelling evidence for timely intervention. Methods A retrospective analysis was conducted on PET/CT imaging data of 170 subsolid nodules lesions confirmed postoperatively as lung adenocarcinoma or precursor glandular lesions. Lesions were categorized into preinvasive lesions including atypical adenomatous hyperplasia and adenocarcinoma in situ, microinvasive adenocarcinoma, and invasive adenocarcinoma. Compared the differences in imaging features and metabolic parameters among different groups and used a multifactor logistic regression model and receiver operating characteristic curve analysis to identify predictive factors for invasive adenocarcinoma. Results From preinvasive lesions through microinvasive adenocarcinoma to invasive adenocarcinoma, there was a gradual increase in nodule diameter, nodule area, and proportion of part-solid nodule. Statistical significance (P < 0.05) was observed in the rates of spiculation and pleural indentation between preinvasive lesions versus microinvasive adenocarcinoma and invasive adenocarcinoma groups. The maximum standardized uptake value and maximum standardized uptake ratio show statistically significant differences (P < 0.05) between the invasive adenocarcinoma group and the other groups. Logistic regression analysis indicated that nodule composition, nodule diameter, and maximum standardized uptake ratio were predictive factors for invasive adenocarcinoma (P < 0.05). For part-solid nodules, the longest diameter of the solid component has a high diagnostic value. Conclusion The imaging features of 18F-FDG PET/CT contribute to the diagnosis of infiltrative subsolid nodules at different stages of lung adenocarcinoma, providing robust evidence for timely intervention.

MA09.09 Genomic Mapping of Evolutionary from Pre-Invasive to Advanced Stage in Lung Adenocarcinoma

MA09.09 Genomic Mapping of Evolutionary from Pre-Invasive to Advanced Stage in Lung Adenocarcinoma

Optimization of Exocrine Pancreatic Insufficiency in Pancreatic Adenocarcinoma Patients.

This study explores the optimization of exocrine pancreatic insufficiency (EPI) management in pancreatic adenocarcinoma patients, focusing on the scientific advancements and technological interventions available to improve patient outcomes, including oral pancreatic enzyme replacement therapy (PERT) and immobilized lipase cartridge (RELiZORB®). This was a prospective Institutional Review Board (IRB)-approved study from October 2019 through to August 2021 at the Louisville Medical Center in collaboration with Norton Healthcare and the University of Louisville Division of Surgical Oncology. Patients with a diagnosis of pancreatic adenocarcinoma (Stage 2 or 3) who underwent oncologic surgical resection were included in this study. Patients were contacted at pre-defined intervals (prior to surgery, before hospital discharge, and 2, 4, 6, and 12 weeks after surgery) to complete nutrition evaluation, EPI assessment, and quality of life questionnaires to identify the severity and frequency of gastrointestinal (GI) symptoms. EPI symptoms were reported in 28 of the 35 total patients studied (80%). Jejunostomy tubes were placed during oncologic surgery in 25 of the 35 total patients studied (71%), and 12 of the 25 patients with a jejunostomy tube utilized enzyme cartridges to manage EPI symptoms while on supplemental tube feeding (48%). EPI symptoms were reported in 8 of the 10 patients without a feeding tube (80%), and their EPI symptoms were managed with PERT alone. EPI interventions, both oral PERT and immobilized cartridges, were associated with a decrease in EPI symptoms after surgery and improved quality of life (QOL). Overall, early optimization of EPI is crucial to enhance overall patient care, return to oncology therapy after surgery, and improve quality of life in pancreatic adenocarcinoma patients.

Evaluation of vascular invasion in pancreatic head tumors and its impact on radical surgical treatment

Objective. To evaluate the informativeness and sensitivity of radiological criteria for vascular invasion in pancreatic head tumors in comparison with intraoperative data and results of routine pathological examination. Materials and methods. The study included 98 patients with ductal adenocarcinoma of the pancreatic head with suspected venous invasion and spread of tumor growth along the vessels of the portomesenteric axis, who were operated on at the Department of Pancreatic and Bile Duct Surgery of the National Research Center of Surgery and Transplantation named after O. A. Shalimov in the period from 2019 to 2023. Group 1 included 51 (52.0%) patients who underwent radical surgery with resection of the superior mesenteric/hepatic portal vein and extended lymph and neurodissection, and group 2 included 47 (48.0%) patients who had positive vascular margins of pancreatic resection according to routine pathological examination. Diagnostic criteria for vascular alterations were developed. A comparative analysis of the informativeness of the developed criteria and the results of a routine pathological examination was performed. The edges of the pancreatic resection were evaluated, including the neck of the gland, common bile duct, duodenum/gastric duct, and the bed of the superior mesenteric/hepatic portal vein and superior mesenteric artery separately. R1 status was defined as the presence of tumor cells at a distance of less than 1 mm to the resection margin. Results. According to the criteria of the National Comprehensive Cancer Network (NCCN) 2023.2, 61 (62.2%) patients had a marginally resectable stage of ductal adenocarcinoma of the pancreatic head and tumor contact with the superior mesenteric/hepatic veins according to multislice computed tomography of the abdominal cavity. In group 1, there were 36 (70.6%) such patients, in group 2 – 25 (53.2%). According to the proposed radiologic criteria for vascular invasion, tumor contact with the superior mesenteric/hepatic portal veins was suspected in 76 (77.6%) patients, which is higher than in the standard approach. Determination of vascular alterations according to the results of our study is a more reliable method for diagnosing invasion of the superior mesenteric/hepatic portal vein (χ2 = 5.46, p = 0.019) and predicting the performance of radical surgery, including vascular resection. Conclusions. The proposed criteria for the radiological diagnosis of vascular invasion at the preoperative stage increased the sensitivity of this method from 62.2 to 77.6%. The most frequent radiological signs of vascular alteration are vascular wall irregularity (47.7%) and parapancreatic tissue density (62.5%). In the presence of any of the radiological signs of vascular alteration, resection of the affected area of the superior mesenteric/hepatic portal vein with extended lymph and neurodissection is indicated, which allows a statistically significant increase in the number of R0 resections.

Prognostic Role of Specific KRAS Mutations Detected in Aspiration and Liquid Biopsies from Patients with Pancreatic Cancer

Background/Objectives: Although the overall survival prognosis of patients in advanced stages of pancreatic ductal adenocarcinoma (PDAC) is poor, typically ranging from days to months from diagnosis, there are rare cases of patients remaining in therapy for longer periods of time. Early estimations of survival prognosis would allow rational decisions on complex therapy interventions, including radical surgery and robust systemic therapy regimens. Understandably, there is great interest in finding prognostic markers that can be used for patient stratification. We determined the role of various KRAS mutations in the prognosis of PDAC patients using biopsy samples and circulating tumor DNA. Methods: A total of 118 patients with PDAC, clinically confirmed by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNB), were included in the study. DNA was extracted from cytological slides following a standard cytology evaluation to ensure adequacy (viability and quantity) and to mark the tumor cell fraction. Circulating tumor DNA (ctDNA) was extracted from plasma samples of 45 patients in stage IV of the disease. KRAS mutations in exons 12 and 13 were detected by denaturing capillary electrophoresis (DCE), revealing a minute presence of mutation-specific heteroduplexes. Kaplan–Meier survival curves were calculated for individual KRAS mutation types. Results:KRAS mutations were detected in 90% of tissue (106/118) and 44% of plasma (20/45) samples. All mutations were localized at exon 2, codon 12, with G12D (GGT > GAT) being the most frequent at 44% (47/106) and 65% (13/20), followed by other types including G12V (GGT > GTT) at 31% (33/106) and 10% (2/20), G12R (GGT > CGT) at 17% (18/106) and 10% (2/20), G12C (GGT/TGT) at 5% (5/106) and 0% (0/20) and G12S (GGT/AGT) at 1% (1/106) and 5% (1/20) in tissue and plasma samples, respectively. Two patients had two mutations simultaneously (G12V + G12S and G12D + G12S) in both types of samples (2%, 2/106 and 10%, 2/20 in tissue and plasma samples, respectively). The median survival of patients with the G12D mutation in tissues was less than half that of other patients (median survival 101 days, 95% CI: 80–600 vs. 228 days, 95% CI: 184–602), with a statistically significant overall difference in survival (p = 0.0080, log-rank test), and furthermore it was less than that of all combined patients with other mutation types (101 days, 95% CI: 80–600 vs. 210 days, 95% CI: 161–602, p = 0.0166). For plasma samples, the survival of patients with this mutation was six times shorter than that of patients without the G12D mutation (27 days, 95% CI: 8–334 vs. 161 days, 95% CI: 107–536, p = 0.0200). In contrast, patients with detected KRAS G12R in the tissue survived nearly twice as long as other patients in the aggregate (286 days, 95% CI: 70–602 vs. 162 days, 95% CI: 122–600, p = 0.0374) or patients with other KRAS mutations (286 days, 95% CI: 70–602 vs. 137 days, 95% CI: 107–600, p = 0.0257). Conclusions: Differentiation of specific KRAS mutations in EUS-FNB and ctDNA (above all, the crucial G12D and G12R) is feasible in routine management of PDAC patients and imperative for assessment of prognosis.

9334 Pancreatic Adenocarcinoma Presenting As Diabetic Ketoacidosis

Abstract Disclosure: J. Alvarez: None. M.H. Horani: None. Background: Pancreatic adenocarcinoma is often diagnosed at an advanced stage due to late onset of clinical features including poor appetite, weight loss, weakness, epigastric pain, and rarely impaired glucose tolerance. In patients who present with impaired glucose tolerance or diabetic ketoacidosis without prior history of diabetes, pancreatic adenocarcinoma should be considered. Clinical Case: Patient is a 45-year woman with depression, HTN, irritable bowel syndrome who was found unresponsive by family and presented to the ED for acute encephalopathy. On exam, she was obtunded, tachypneic, with fruity-smelling breath and dry mucous membranes. Initial labs showed glucose of 950 mg/dL (70-99 mg/dL), lipase 539 U/L (8-78 U/L), lactic acid 4 mmol/L 0.5-2 mmol/L), ketone-BHB 170.75 mg/dL (0-2.81 mg/dL), A1c 16.5%. She had no prior history or family history of diabetes. She was admitted to hospital for DKA management.CXR to evaluate dyspnea showed bilateral opacities so CT chest/abdomen/pelvis without contrast was ordered. This showed bilateral multilobar pneumonia, trace pleural effusions, 6.7 x 3.8 cm lobulated fluid collection along pancreatic tail, 12.1 x 6.6 x 4.4 cm RLQ cystic lesion and 4.4 cm lesion vs loculation along the right pelvic sidewall.Initially, GI recommended repeat imaging of the pancreas in 4-6 weeks. OBGYN was consulted for pelvic masses and recommended IR-guided biopsy of right pelvic mass which showed rare mildly atypical mucinous epithelium present, cystic mucinous neoplasm cannot be excluded.CEA and CA125 tumor markers returned elevated. These biopsies showed adenocarcinoma (solid component) and rare atypical mucinous epithelium consistent with cystic mucinous neoplasm (cystic fluid). Patient was deemed medically stable for discharge with recommended follow-up to appropriate specialists. Following discharge, she was officially diagnosed with Stage III (cT4, cN0, cM0) pancreatic adenocarcinoma and started on appropriate chemotherapeutic regimen. Discussion: The current understanding is long-standing type 2 diabetes mellitus as a risk factor for pancreatic cancer based on previous studies.The inverse relationship of pancreatic cancer causing new onset diabetes is more rare, but if cancer is suspected in these patients it could potentially help in the diagnosis of early stage adenocarcinoma. Other case reports have suggested implementation of the enriching new-onset diabetes for pancreatic cancer (ENDPAC) score in addition to CT and EUS as screening for pancreatic cancer may help with earlier diagnosis.

Possibilities and limitations of magnetic resonance imaging in the diagnostics of endocervical adenocarcinomas

BACKGROUND: In recent decades, the incidence of cervical adenocarcinomas has increased from 5% to 20%. Endocervical adenocarcinomas are characterized by a more aggressive course and early metastasis. Owing to the difficulties in the cytological diagnosis of cervical adenocarcinoma, early radiation diagnostics and staging subsequently play a key role. Very few studies have examined the use of magnetic resonance imaging in diagnosing cervical adenocarcinomas. AIM: To determine the diagnostic informativeness of magnetic resonance imaging in the staging of cervical adenocarcinomas according to the T-criterion and assessing the depth of tumor invasion into the stroma of the cervix and clarify the semiotic signs of adenocarcinoma and features of tumor growth in the uterus. MATERIALS AND METHODS: In total, 123 patients diagnosed with cervical cancer (C53), who underwent diagnosis and treatment between 2020 and 2023, were examined. The examination results of 22 (18%) patients with cervical adenocarcinoma were analyzed. The average patient age was 56 years. A multiparametric magnetic resonance examination of the pelvic organs was performed on 22 patients using tomographs with a magnetic field strength of 1.5 T. Moreover, 14 (64%) patients underwent surgery including extirpation of the uterus and appendages with pelvic lymphadenectomy. The information value of magnetic resonance imaging was evaluated in 11 patients, whose first stage was surgical treatment. RESULTS: In this study, cervical adenocarcinoma was detected in 18% among all cases of cervical cancer. The information value of magnetic resonance imaging in assessing the local prevalence of endocervical adenocarcinoma according to the T-criterion was as follows (main value with the corresponding 95% confidence interval): sensitivity, 77.78% (39.99%–97.19%); specificity, 50.00% (1.26%–98.74%); positive predictive value, 87.50% (62.64%–96.69%); negative predictive value, 33.33% (7.30%–76.04%); and accuracy, 72.73% (39.03%–93.98%). The information value of magnetic resonance imaging in assessing the depth of tumor invasion into the cervical stroma was as follows: odds ratio, 3.500 (0.145%–84.694%); sensitivity, 85.7% (0.757%–0.993%); specificity, 33.3% (0.018%–0.0648%); positive predictive value, 75% (0.673%–0.883%); negative predictive value, 50% (0.027%–0.972%). CONCLUSIONS: The results of this study showed that magnetic resonance imaging is a good tool with high diagnostic informativeness in detecting endocervical cervical adenocarcinoma. The four macrostructures of tumor growth in endocervical adenocarcinoma identified during magnetic resonance imaging data analysis indicate locally aggressive tumor growth and a high frequency of endometrial dropouts. This finding will allow radiologists to structure a descriptive picture, including the verified cervical adenocarcinoma, to enhance methods of developing a treatment plan for the patient.

Human intermediate prostate cancer stem cells contribute to the initiation and development of prostate adenocarcinoma

BackgroundIntermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells.MethodsWe developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures.ResultsWe found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro.ConclusionsOur study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.

“Find Your Y”: histological differences in early stage (pT) and post-treatment (ypT) oesophageal adenocarcinoma with implications for salvage endoscopic resection

AimsCurrent guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited....

Cell states and neighborhoods in distinct clinical stages of primary and metastatic esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a highly lethal cancer of the upper gastrointestinal tract with rising incidence in western populations. To decipher EAC disease progression and therapeutic response, we performed multiomic analyses of a cohort of primary and metastatic EAC tumors, incorporating single-nuclei transcriptomic and chromatin accessibility sequencing, along with spatial profiling. We identified tumor microenvironmental features previously described to associate with therapy response. We identified five malignant cell programs, including undifferentiated, intermediate, differentiated, epithelial-to-mesenchymal transition, and cycling programs, which were associated with differential epigenetic plasticity and clinical outcomes, and for which we inferred candidate transcription factor regulons. Furthermore, we revealed diverse spatial localizations of malignant cells expressing their associated transcriptional programs and predicted their significant interactions with microenvironmental cell types. We validated our findings in three external single-cell RNA-seq and three bulk RNA-seq studies. Altogether, our findings advance the understanding of EAC heterogeneity, disease progression, and therapeutic response.

Quantitative Edge Analysis Can Differentiate Pancreatic Carcinoma from Normal Pancreatic Parenchyma.

This study aimed to introduce specific image feature analysis, focusing on pancreatic margins, and to provide a quantitative measure of edge irregularity, evidencing correlations with the presence/absence of pancreatic adenocarcinoma. We selected 50 patients (36 men, 14 women; mean age 63.7 years) who underwent Multi-detector computed tomography (MDCT) for the staging of pancreatic adenocarcinoma of the tail of the pancreas. Computer-assisted quantitative edge analysis was performed on the border fragments in MDCT images of neoplastic and healthy glandular parenchyma, from which we obtained the root mean square deviation SD of the actual border from the average boundary line. The SD values relative to healthy and neoplastic borders were compared using a paired t-test. A significant SD difference was observed between healthy and neoplastic borders. A threshold SD value was also found, enabling the differentiation of adenocarcinoma with 96% specificity and sensitivity. We introduced a quantitative measure of boundary irregularity, which correlates with the presence/absence of pancreatic adenocarcinoma. Quantitative edge analysis can be promptly performed on select border fragments in MDCT images, providing a useful supporting tool for diagnostics and a possible starting point for machine learning recognition based on lower-dimensional feature space.

In Pursuit of Novel Markers: Unraveling the Potential of miR-106, CEA and CA 19-9 in Gastric Adenocarcinoma Diagnosis and Staging.

Gastric cancer stands as the fourth leading cause of cancer-related deaths globally, primarily comprising adenocarcinomas, categorized by anatomic location and histologic type. Often diagnosed at advanced stages, gastric cancer prognosis remains poor. To address the critical need for accurate tumoral markers for gastric cancer diagnosis, we conducted a study to assess classical markers like CEA and CA-19-9 alongside the novel marker miR-106. Our investigation revealed distinct dynamics of these markers compared to non-cancerous groups, although no disparities were observed across different disease stages. Univariable and multivariable logistic regression analyses demonstrated that elevated levels of miR-106, CEA and CA 19-9 were predictive of a positive histopathological exam, with the respective odds ratios of 12.032 (95% CI: 1.948-74.305), 30 (95% CI: 3.141-286.576), and 55.866 (95% CI: 4.512-691.687). Subsequently, we utilized predicted probabilities from regression models to construct receiver operating characteristic (ROC) curves, identifying CA 19-9 as the optimal predictor for gastric adenocarcinoma diagnosis when considering age and gender, with an area under the curve (AUC) of 0.936 (p < 0.001). Hence, classical markers exhibit superior performance compared to the novel marker miR-106 in predicting gastric adenocarcinoma.

Histopathological Study of Gastric Adenocarcinoma with Special Reference to Expression of HER2/neu and Ki-67 Assessed by Immunohistochemistry

Abstract Introduction Gastric cancer has become the third leading cause of cancer deaths globally. It accounts for 5.7% of cancer around the world, with a rate of mortality around 8.2%. Evaluation of human epidermal growth factor receptor 2 (HER2)/neu overexpression for targeted therapies is presently the mainstay of treatment in gastric cancer. High Ki-67 index expression in gastric cancer is an indicator of poor prognosis. Objectives To study the prevalence of HER2/neu expression and Ki-67 index in various types, sites, grade, and stage of gastric adenocarcinoma and to determine the correlation between HER2/neu expression and Ki-67 index. Materials and Methods This is a prospective study in a tertiary care hospital, Kolkata from January 2019 to June 2020. Gastrectomy and endoscopic biopsy of gastric adenocarcinoma were studied for histopathology and immunohistochemistry (HER2/neu and Ki-67 index). Statistical analysis used: SPSS (version 21.0, IBM, Chicago, Illinois, United States) for windows software. Results Among 54 cases, most of them were intestinal type, antral, moderately differentiated, stage III cases. HER2 expression and high Ki-67 index were observed in 28.0 and 40.75% cases, respectively. Statistically significant correlation was found in both HER2 expression and high Ki-67 index with location of the tumor and pathological nodal (pN) stage. A positive correlation was found between HER2/neu score and Ki-67 index (p = 0.007) (correlation coefficient = 0.4). Conclusion A positive correlation was found between HER2/neu positivity and high Ki-67 index, both were associated with higher pathological tumor stage and pN stage. So, advanced cases may be considered for targeted therapy using trastuzumab.

Next-generation sequencing as a valuable tool for mutational spectrum in advanced-stage NSCLC patients.

Lung cancer remains one of the most threatening malignancies, ranking as the second most diagnosed cancer, and it continues to be the leading cause of cancer-related deaths worldwide. Challenges persist with late diagnosis and the high mutational burden characteristic of lung cancer. Our study focuses on identifying the mutational spectrum of a cohort of advanced-stage non-small cell lung cancer (NSCLC) patients using a minimally invasive method through blood collection. To analyze the mutational landscape of these patients, we employed plasma DNA for the next-generation sequencing (NGS) cancer panel Ion Torrent, which contains 50 of the most mutated genes in lung cancer. All protocols for extraction, quality and quantity control, and library preparation follow the manufacturer's rules. Bioinformatics analysis was performed to select pathogenic mutations versus non-pathogenic-benign ones. This approach is particularly valuable for patients in advanced stages (III and IV, n=10) of lung adenocarcinoma and lung squamous cell carcinoma, who lack surgical options and limited therapeutic avenues. The comprehensive sequencing analysis revealed that nine of the ten lung cancer patients carried a TP53 mutation. Also, several other mutations exist in various cases, showing heterogeneous profiling. Our findings demonstrate the potential of liquid biopsies in providing crucial genetic insights that can guide personalized treatment strategies, improving the management and outcomes for patients with advanced lung cancer.

Biomonitoring Study of Toxic Metal(loid)s: Levels in Lung Adenocarcinoma Patients.

Lung cancer is a leading cause of cancer deaths worldwide. The aim of this study was to investigate heavy metal(loid)s (Cd, Pb, Hg, Cr, Mn, Mo, Ni, and As) in lung cancer patients in order to elucidate their role as lung cancer environmental risk factors. Sixty-three patients of both sexes with adenocarcinoma stage IIIB or IV were enrolled in this research. The heavy metal(loid) urine concentrations were measured using ICP-MS. Arsenic was quantified above 10 μg/L in 44.44% of the samples. Nickel urinary concentrations above the ToxGuide reference levels were found in 50.79% of the samples, while lead was quantified in 9.52% of the urine samples. The urinary chromium levels were above the mean ToxGuide levels in 41.27% of the patients and were significantly higher in men in comparison with women (p = 0.035). The chromium urinary concentrations were positively associated with the CRP serum levels (p = 0.037). Cadmium was quantified in 61.90% of the samples with levels significantly higher in females than in males (p = 0.023), which was associated with smoking habits. Mercury was measured above the limit of quantification in 63.49% of the samples and was not associated with amalgam dental fillings. However, the Hg urinary concentrations were correlated positively with the ALT (p = 0.02), AST (p < 0.001), and GGT (p < 0.001) serum levels. In 46.03% of the samples, the Mo concentrations were above 32 μg/L, the mean value for healthy adults according to the ToxGuide, and 9.52% of the patients had Mn levels higher than 8 μg/L, the reference value for healthy adults based on ToxGuide data. The obtained results are preliminary, and further studies are needed to have a deeper insight into metal(loid) exposure's association with lung cancer development, progression, and survival prediction.

A Phase II Trial of Celecoxib with Neoadjuvant Concurrent Chemoradiation for Patients with Localized Rectal Adenocarcinoma Stage II and III

Abstract Background In recent years, neoadjuvant chemoradiation and subsequent surgical resection with total mesorectal excision has been shown to increase local control with decreased toxicity in comparison to upfront surgical resection followed by adjuvant chemoradiation. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluated the efficacy of adding a selective COX-2 inhibitor to standart neoadjuvant chemoradiation on pathologic response, sphincter preservation and acute toxicity. Materials and Methods Thirty patients with Adenocarcinoma of rectum (up to 15 cm of anal verge) were enrolled in this phase 2 study. Patients undergone full colonoscopy, MRI rectal protocol, abdomino-pelvic and chest CT scan for staging then received neoadjuvant concurrent chemoradiation (capecitabine 825 mg/m2 bid in combination with celecoxib 200 mg bid and radiotherapy (50-50.4Gy/25-28fraction). Surgery was done 5-12 weeks after chemoradiation. Acute complications were scored by common toxicity criteria 5.0 and tumor response was graded according to AJCC and CAP guidelines for rectal adenocarcinoma. Results Of 30 patients, total mesorectal excision was done in 22 patients. Tumor regression grade was reported as: 7 patients (31.8%) had grade 0 or complete response, 7 patients (31.8%) had grade 1 or moderate response, 6 patients (27%) had grade 2 or minimal response and 2 patients (9%) had grade 3 or poor response. Primary tumor down staging was 63% and nodal down staging was 73% with sphincteric preservation rate of 77% among the operated cohort. No patients had hematologic or cardio-vascular toxicity. Conclusion Results indicate celecoxib in combination with neoadjuvant chemoradiation is safe and associated with low toxicity. This combination can promote pathologic complete response, tumor regression grade, sphincteric preservation, T and N down staging in rectal adenocarcinoma.

Highly consistency of PIK3CA mutation spectrum between circulating tumor DNA and paired tissue in lung cancer patients

BackgroundPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are associated with drug resistance and prognosis in lung cancer; however, the consistency and clinical value of PIK3CA mutations between tissue and liquid samples are unknown. MethodsCirculating tumor DNA (ctDNA) and matched tumor tissue samples from 405 advanced lung cancer patients were collected at Jilin Cancer Hospital between 2018 and 2022, and the PIK3CA mutation status was sequenced using next-generation sequencing based on a 520 gene panel. The viability of different mutant lung cancer cells was detected using MTT assay. ResultsPIK3CA mutations were detected in 46 (5.68 %) of 810 lung cancer samples, with 21 (5.19 %) of 405 plasma samples and 25 (6.17 %) of 405 matched tissues. p.Glu542Lys, p.Glu545Lys, and p.His1047Arg were the most common mutation types of PIK3CA in both the ctDNA and tissue samples. The concordance of PIK3CA mutations was 97.53 % between ctDNA and matched tissues (kappa: 0.770, P = 0.000), with sensitivity/true positive rate of 72.0 %, specificity/true negative rate of 99.2 %, and negative predictive value and positive predictive value of 0.982 and 0.857, respectively (AUC = 0.856, P = 0.000). Furthermore, the concordance of PIK3CA mutations was 98.26 % in lung adenocarcinoma and 96.43 % in lung squamous cell carcinoma. TP53 and EGFR were the most common concomitant mutations in ctDNA and tissues. Patients with PIK3CA mutations showed a high tumor mutational burden (TMB) (P < 0.001) and a significant correlation between bTMB and tTMB (r = 0.5986, P = 0.0041). For the tPIK3CAmut/ctDNA PIK3CAmut cohort, PI3K pathways alteration was associated with male sex (P = 0.022), old age (P = 0.007), and smoking (P = 0.001); tPIK3CAmut/ctDNA PIK3CAwt patients harbored clinicopathological factors of adenocarcinoma stage IV, with low PS score (≤1) and TMB. ConclusionThis study showed that ctDNA is highly concordant and sensitive for identifying PIK3CA mutations, suggesting that PIK3CA mutation detection in liquid samples may be an alternative clinical practice for tissues.

Evaluating the necessity of lymph node sampling in lung adenocarcinoma with ground glass opacities

BackgroundGround glass opacity is observed frequently in the early stages of lung adenocarcinoma and is associated with a favorable prognosis and a low incidence of lymph node metastasis. However, the necessity of lymph node sampling in these patients is questionable, although current guidelines still recommend it. MethodsRadiologic and clinical data were retrospectively collected and analyzed for 2,298 patients with lung cancer who underwent surgical resection for lesions ≤15 mm during 2022. Based on the consolidation tumor ratios, patients were categorized into 4 groups (pure ground glass opacity, ground glass opacity-predominant, solid-predominant, and pure solid). The incidence of lymph node metastasis in each group was examined. ResultsA total of 2,298 patients with a median age of 54.0 years were enrolled in this study. Tumors were categorized into 4 types: 1,427 (62.1%) were pure ground glass opacity, which constituted the majority, while 421 (18.3%) were ground glass opacity-predominant, 330 (14.4%) were solid-predominant, and the remaining 120 (5.2%) were pure solid. Significant positive correlations were revealed between the consolidation tumor ratio group and pathologic grade (P < .001, ρ = 0.307), T stage (P < .001, ρ = 0.270), and N stage (P < .001, ρ = 0.105). Among the included cases, only 7 cases with metastasis were in the pure solid group. Within this group, 113 cases (94.2%) were N0, 5 cases (4.2%) were N1, and 2 cases (1.7%) were N2. ConclusionLymph node metastasis exclusively occurred in the pure solid group, suggesting that for nodules <15 mm, lymph node sampling may be crucial for pure solid nodules but less so for those containing ground glass opacities.