Small Adenocarcinoma Research Articles

Cell renewal index in the differential diagnosis of atypical small acinar proliferation and adenocarcinoma of the prostate

Introduction Singling out such diagnostic category as atypical small acinar proliferation of the prostate (ASAP) determines the necessity of forming additional approaches to differential morphological diagnosis in order to determine adenocarcinoma in time. Cell renewal index (CRI) is actively used to study proliferation and apoptosis in the epithelial cells of hormone-dependent glands, but in prostate pathology this criterion has not been studied.The aim of the study was to characterize the cell renewal index in atypical small acinar proliferation and prostate adenocarcinoma of different degrees of differentiation in order to optimize differential diagnosis.Materials and methods We studied 720 prostate biopsy specimens from 60 patients: Group 1 — 15 patients with ASAP; Group 2 − 15 with adenocarcinoma of high-grade of differentiation; Group 3 − 15 with moderately differentiated adenocarcinoma; Group 4 − 15 with low differentiated adenocarcinoma. We used immunohistochemical method (Ki-67, CPP32) and non-parametric statistical methods of investigation.Results The CRI in ASAP was comparable to that in highly differentiated adenocarcinoma (p=0.5). In moderately differentiated adenocarcinoma the CRI was significantly higher than in ASAP and highly differentiated adenocarcinoma (p=0.004). The greatest increase in CRI was noted in the low-differentiated adenocarcinoma group, which was higher and significantly different from the ASAP (p=0.000), highly differentiated carcinoma (p=0.003) and moderately differentiated prostatic carcinoma (p=0.000) groups.Discussion On the basis of statistical analysis the present study helped to reveal the identity of CRI parameters in ASAP and highly differentiated adenocarcinoma of the prostat, which allows to add a number of morphological criteria for transferring patients from the group of undetermined diagnosis of ASAP to the group of adenocarcinoma. There is a need for further investigation of CRI with multiparametric analysis including investigation of the expression levels of hormones involved in the regulation of cell renewal in the prostate and growth factors associated with them.Conclusion The study allowed to reveal the identity of the CRI in ASAP and highly differentiated adenocarcinoma of the prostate, which can supplement a number of morphological criteria for transferring patients from the group of undeterminate diagnosis of ASAP to the group of adenocarcinoma.

Abstract 3614: 3D model to study migration and invasion of lung cancer

Abstract Background: In 2D cell cultures, migration of tumor cells is characterized by epithelial-to-mesenchymal transition (EMT), whereby tumor cells loose epithelial and express mesenchymal markers and very often change into a spindle cell phenotype. In contrast to 2D cultures, in 3D cultures tumor cells do not lose their differentiation. Small cell lung cancer usually moves as single cells or in small clusters, squamous cell and adenocarcinomas preferentially move in large clusters of cells. In tissue specimen, all of these carcinomas migrate in a hybrid EMT, not loosing their cytokeratin and E-cadherin expression. In AC and SCC also polarity and specification do occur, as some tumor cells act as leaders, providing orientation for the followers. However, 3D culture system might better depict real migration and come closer to the in vivo system as 2D cell culture systems. Material and Method: A 3D bioprinter (TissueLabsR) was used to spot an alveolar-mimicking lung-specific matrix on cell culture wells. Microscopic channels out of pluronicsR are created within the matrix. Pluronics is removed by cooling, leaving empty channels within the protein matrix. These channels can be filled with different interleukins, such as IL23, which will direct migration of the tumor cells. Cultured cell lines from an adenocarcinoma (A549) and small cell carcinoma (NCI-H82) are layered on top of the matrix and migration into the matrix is studied using different time points. Results and Discussion: A matrix simulating an alveolar structure was created with MatrigelR. The A549 cells were seeded on the matrix and grown for 2,5, 10, and 14 days. The cells formed cell clusters on the matrix and after one week started to invade the matrix in cell complexes. By immunohistochemistry we could show, that the A549 cells retained their epithelial differentiation. The H82 cells showed a different behavior. They did not form large clusters, but started to invade in small groups. The use of the bioprinter enabled us not only to create a 3D tumor culture system to simulate the in vivo conditions but also to create matrix structures for studying invasion and migration and to stimulate carcinoma cells with migration-activating substances. Citation Format: Melina Hardt, Kurt Zatloukal, Helmut H. Popper. 3D model to study migration and invasion of lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3614.

In-depth proteomics reveals the characteristic developmental profiles of early lung adenocarcinoma with epidermal growth factor receptor mutation.

Lung adenocarcinoma progresses stepwise from atypical adenomatous hyperplasia to adenocarcinoma in situ (AIS), followed by minimally invasive adenocarcinoma (MIA), and then obvious invasive adenocarcinoma. In this study, we examined the protein expression profiles of early and epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinomas. Fifteen cases of small and EGFR mutation-positive adenocarcinomas were collected, including AIS, MIA, and small invasive adenocarcinoma (SIA). We examined their protein expression profiles by tandem mass tag (TMT)-labeling liquid chromatography-mass spectrometry (LC-MS/MS) and compared the results between AIS and MIA versus SIA. The differentially expressed proteins were then verified by Western blot analysis and immunohistochemistry (IHC). The clinicopathological implications of the proteins were also examined by IHC. A total of 4220 proteins were identified by LC-MS/MS analysis. Pathway analysis of the differentially expressed proteins revealed that pathways related to interferon α/β signaling, glutamate and glutamine metabolism, and gluconeogenesis were upregulated in SIA relative to AIS. Among the 13 differentially expressed proteins, cellular retinoic acid binding protein 2 (CRABP2), delta(24)-sterol reductase (DHCR24), and adenylate kinase 4 (AK4) were expressed significantly more strongly in SIA than in AIS. Patients with high expression of CRABP2, DHCR24, and AK4 showed a significantly poorer outcome than those with low expression. In comparison with AIS, SIA shows differences in several different protein expression pathways. Furthermore, CRABP2, DHCR24, and AK4 are useful IHC markers for diagnosis of lung adenocarcinoma invasiveness and may be associated with malignant progression of AIS.

Increased Risk of Colorectal Cancer in Patients With Celiac Disease: A Population-Based Study.

The association between celiac disease (CD) and the development of small bowel lymphoproliferative disorders and esophageal adenocarcinoma has been established in the literature. However, there is only a little evidence demonstrating an increased risk of colorectal cancer (CRC) in patients with CD. Hence, we conducted a cross-sectional population-based study to evaluate the risk of developing CRCin patients who have had a diagnosis of CD. We used a commercial database (Explorys Inc, Cleveland, OH), which includeselectronic health records from 26 major integrated US healthcare systems. Patients aged 18-65 years were included. Patients with inflammatory bowel disease (IBD) were excluded. Multivariate analysis using backward stepwise logistic regression was performed to calculate the risk of developing CRCin potential confounders. A two-sided P-value <0.05 was considered statistically significant. 79,843,332 individuals were screened in the database and 47,400,960 were selected in the final analysis after accounting for inclusion and exclusion criteria. Using a stepwise multivariate regression analysis, the odds of having CRC amongpatientswith CD was 10.18 (95% CI 9.72-10.65) (P-value <0.001). The odds also remained high amongmales 1.49 (95% CI 1.36-1.63), African Americans 1.51 (95% CI 1.35-1.68), patients who have type 2 diabetes mellitus (T2DM) 2.71 (95% CI 2.66-2.76), are smokers 2.49 (95% CI 2.44-2.54), are obese 2.21 (95% CI 2.17-2.25), and are alcoholic 1.72 (95% CI 1.66-1.78). Our study demonstrates that patients with CD are frequently found to have CRCeven when adjusting for common risk factors. This adds to the literature and helps spread awareness to clinicians that the effects of CD are not only limited to the small bowel as the disease tends to involve other parts of the gastrointestinal tract also, especially the colon. The threshold to screen patients with CD should be considered to be lowered.

CT radiomics model combined with clinical and radiographic features for discriminating peripheral small cell lung cancer from peripheral lung adenocarcinoma.

Exploring a non-invasive method to accurately differentiate peripheral small cell lung cancer (PSCLC) and peripheral lung adenocarcinoma (PADC) could improve clinical decision-making and prognosis. This retrospective study reviewed the clinicopathological and imaging data of lung cancer patients between October 2017 and March 2022. A total of 240 patients were enrolled in this study, including 80 cases diagnosed with PSCLC and 160 with PADC. All patients were randomized in a seven-to-three ratio into the training and validation datasets (170 vs. 70, respectively). The least absolute shrinkage and selection operator regression was employed to generate radiomics features and univariate analysis, followed by multivariate logistic regression to select significant clinical and radiographic factors to generate four models: clinical, radiomics, clinical-radiographic, and clinical-radiographic-radiomics (comprehensive). The Delong test was to compare areas under the receiver operating characteristic curves (AUCs) in the models. Five clinical-radiographic features and twenty-three selected radiomics features differed significantly in the identification of PSCLC and PADC. The clinical, radiomics, clinical-radiographic and comprehensive models demonstrated AUCs of 0.8960, 0.8356, 0.9396, and 0.9671 in the validation set, with the comprehensive model having better discernment than the clinical model (P=0.036), the radiomics model (P=0.006) and the clinical-radiographic model (P=0.049). The proposed model combining clinical data, radiographic characteristics and radiomics features could accurately distinguish PSCLC from PADC, thus providing a potential non-invasive method to help clinicians improve treatment decisions.

The Role of MRI in the Diagnosis of Solid Pseudopapillary Neoplasm of the Pancreas and Its Mimickers: A Case-Based Review with Emphasis on Differential Diagnosis.

Solid pseudopapillary neoplasm (SPN) is rare pancreatic tumor occurring most commonly in young females. The typical imaging appearance of SPN is of well-defined, encapsulated, and large heterogeneous tumors, consisting of solid and cystic components due to various degrees of intralesional hemorrhage and necrosis. However, atypical imaging presentation in the form of small solid tumors or uniformly cystic lesions might also be seen, which can be explained by specific pathological characteristics. Other imaging features such as a round shape, the absence of main pancreatic duct dilatation, and slow growth, in combination with vague symptoms, favor the diagnosis of SPNs. Nevertheless, the radiological findings of SPN might overlap with other solid and cystic pancreatic neoplasms, such as neuroendocrine tumors, serous and mucinous neoplasms, and even small pancreatic adenocarcinomas. In addition, a few benign non-tumorous conditions including walled-of-necrosis, and intrapancreatic accessory spleen may also pose diagnostic dilemmas simulating SPNs on imaging studies. The aim of this manuscript is to provide a comprehensive overview of the typical and atypical imaging features of SPNs and to describe useful tips for differential diagnosis with its potential mimickers.

A relatively high proportion of dogs with small apocrine gland anal sac adenocarcinoma (AGASACA) primary tumours present with locoregional lymph node metastasis.

Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly relevant disease in dogs, with a high rate of lymph node (LN) metastasis during the course of disease. A recent study showed that risk for death and disease progression was significantly associated with primary tumour size less than 2 and 1.3cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2cm in diameter, that are diagnosed with LN metastasis at presentation. This was a single site retrospective study of dogs that underwent treatment for AGASACA. Dogs were included if physical examination primary tumour measurements were available, abdominal staging was performed, and confirmation of abnormal lymph nodes by cytology or histology was done. Over a 5-year period, 116 dogs were included for review with 53 (46%) having metastatic LN at presentation. The metastatic rate for dogs with primary tumours <2cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2cm. The association between tumour size group (<2 vs. ≥2cm) and the presence of metastasis at presentation was significant (P < .0001) with an OR of 7.0 (95% CI: 2.9-15.7). Primary tumour size was significantly associated with LN metastasis at presentation but the proportion of dogs that presented with LN metastasis in the <2cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.

The predictive accuracy of CT radiomics combined with machine learning in predicting the invasiveness of small nodular lung adenocarcinoma.

Conventionally, the judgment of whether small pulmonary nodules are invasive is mainly made by thoracic surgeons according to the chest computed tomography (CT) features of patients. However, there are limits to how much useful information can be obtained from this approach. A large number of feature information was extracted from CT images by CT radiomics. The machine learning algorithm was used to construct models based on radiomic characteristics to predict the invasiveness of lung adenocarcinoma (LUAD) with a good prediction accuracy. A total of 416 patients with pathologically confirmed preinvasive lesions and LUAD after video-assisted thoracoscopic surgery (VATS) in the Department of Thoracic Surgery of the First People's Hospital of Yunnan Province from February 2020 to February 2022 were retrospectively analyzed. According to random classification, patients were divided into 2 groups. The RadCloud platform was used to extract radiomics features, and the most relevant radiomics features were selected by continuous dimension reduction method. Then, 6 machine learning algorithms were used to establish and verify the prediction model of small lung nodular adenocarcinoma invasiveness. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the predictive performance. There were 78 cases of pre-invasive lesions and 226 cases of invasive lesions in the training group, and 34 cases of pre-invasive lesions and 78 cases of invasive lesions in the validation group. In the training group, the AUC values of the 6 models were all more than 0.914, the 95% confidence interval (CI) was 0.857-1.00, the sensitivity was equal or more than 0.87, and the specificity was equal or more than 0.85. In the validation group, the AUC values of the 6 models were all equal or more than 0.732, the 95% CI was 0.651-1.00, the sensitivity was equal or more than 0.7, and the specificity was more than 0.77. Machine learning algorithms were used to construct models to predict the invasiveness of small nodular LUAD based on radiomics features, which it could provide more evidence for doctors to make diagnoses and more personalized treatment plans for patients.

Radical nephroureterectomy followed by adjuvant chemotherapy (RNU-AC) versus observation (RNU-O) in early-stage upper urinary tract cancers with variant histology (UUTC-VH).

487 Background: Upper urinary tract cancers (UUTC) are less frequent and associated with poorer stage-for-stage prognosis compared to bladder cancer, with variant histology being an independent predictor of inferior outcomes. The POUT trial included only patients with predominantly urothelial tumors. We aimed to compare outcomes among patients with UUTC-VH who were treated with RNU-AC vs. RNU-O. Methods: We queried the National Cancer Database for adult patients with UUTC-VH diagnosed between 2004 and 2018. Only patients who underwent RNU with node-negative disease on pathological staging (pT2-4N0M0) were included and divided into two groups based on the postoperative treatment strategy - RNU-AC and RNU-O. Patients who received neoadjuvant chemotherapy were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 522 patients were identified – 133 (25.5%) received RNU-AC while 389 (74.5%) underwent RNU-O. Patients in the RNU-AC group were younger (median 69 vs. 76 years, P &lt;0.001). Patients with small cell (15.8% vs 4.9%), micropapillary (9.8% vs 5.9%) and adenocarcinoma (9% vs 6.7%) histologies were more likely while those with squamous histology was less likely to receive AC (38.3% vs 50.6%) (p &lt; 0.001 for all comparisons). A significant majority of patients in each T stage were treated with AC – 87.1% of pT1, 73.2% of pT2, and 68.4% of pT3 (P = 0.009). Overall survival in the RNU-AC and RNU-O groups were comparable (median of 27 vs 24.1 months, log rank-P = 0.63). On multivariable analysis, neither AC nor histological subtype were not independently predictive of OS (HR for AC = 0.96, 95% CI 0.74-1.24, P = 0.75). Conclusions: This is the largest study to date evaluating outcomes with AC after RNU in UUTC-VH since these patients were largely excluded from AC clinical trials. We observed that AC was not associated with improved overall survival after RNU in this population.

Novel Study of the Effect of Bilobetein Compound and Silver Nano Particles of Ginkgo Biloba as Folate Antagonists by Inhibiting Enzyme Dihydrofolate Reductase in Iraqi Patients Serum of Small Cell and Adenocarcinoma Lung Cancer

Novel Study of the Effect of Bilobetein Compound and Silver Nano Particles of Ginkgo Biloba as Folate Antagonists by Inhibiting Enzyme Dihydrofolate Reductase in Iraqi Patients Serum of Small Cell and Adenocarcinoma Lung Cancer

Factors associated with preoperative and postoperative seizures in patients undergoing resection of brain metastases.

Epileptic seizures are a common and potentially devastating complication of metastatic brain tumors. Although tumor-related seizures have been described in previous case series, most studies have focused on primary brain tumors and have not differentiated between different types of cerebral metastases. The authors analyzed a large surgical cohort of patients with brain metastases to examine risk factors associated with preoperative and postoperative seizures and to better understand the seizure risk factors of metastatic brain tumors. Patients who underwent resection of a brain metastasis at the University of California, San Francisco (UCSF), were retrospectively reviewed. Patients included in the study were ≥ 18 years of age, required resection of a brain metastasis, and were treated at UCSF. Primary cancers included melanoma, non-small cell lung adenocarcinoma, breast adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, renal cell carcinoma, urothelial carcinoma, ovarian carcinoma, cervical squamous cell carcinoma, and endometrial adenocarcinoma. Patients were evaluated for primary cancer type and seizure occurrence, as well as need for use of antiepileptic drugs preoperatively, at time of discharge, and at 6 months postoperatively. Additionally, Engel classification scores were assigned to those patients who initially presented with seizures preoperatively. Univariate and multivariate regression analyses were used to assess the association of tumor type with preoperative seizures. Data were retrospectively analyzed for 348 consecutive patients who underwent surgical treatment of brain metastases between 1998 and 2019. The cohort had a mean age of 60 years at the time of surgery and was 59% female. The mean and median follow-up durations after the date of surgery for the cohort were 22 months and 10.8 months, respectively. In univariate analysis, frontal lobe location (p = 0.05), melanoma (p = 0.02), KRAS mutation in lung carcinoma (p = 0.04), intratumoral hemorrhage (p = 0.04), and prior radiotherapy (p = 0.04) were associated with seizure presentation. Postoperative checkpoint inhibitor use (p = 0.002), prior radiotherapy (p = 0.05), older age (p = 0.002), distant CNS progression (p = 0.004), and parietal lobe tumor location (p = 0.002) were associated with seizures at 6 months postoperatively. The final multivariate model confirmed the independent effects of tumor location in the frontal lobe and presence of intratumoral hemorrhage as predictors of preoperative seizures, and checkpoint inhibitor use and parietal lobe location were identified as significant predictors of seizures at 6 months postoperatively. Within this surgical cohort of patients with brain metastases, seizures were seen in almost a quarter of patients preoperatively. Frontal lobe metastases and hemorrhagic tumors were associated with higher risk of preoperative seizures, whereas checkpoint inhibitor use and parietal lobe tumors appeared to be associated with seizures at 6 months postoperatively. Future research should focus on the effect of metastatic lesion-targeting therapeutic interventions on seizure control in these patients.

99. Histopathologic Correlation Somatic Variants in Non Small Cell Lung Cancer with High Tumor Mutation Burden

<h3>Introduction</h3> High tumor mutation burden (TMB), having at least 10 mutations/megabase (mut/Mb), is reported to be as high as 42% of non small cell lung adenocarcinoma (LADC). Micropapillary adenocarcinoma is one of the most aggressive histologic subtypes of lung adenocarcinoma (LADC) and is often associated with a poor prognosis. <h3>Methods</h3> We performed next-generation sequencing (NGS) with and explored histologic and molecular features in 33 consecutive TMB High LADC utilizing the Ion Oncomine Comprehensive Panel Plus (OCAPlus). <h3>Results</h3> LADC with high tumor mutation burdens (TMBs) were more likely to display necrosis, as well as papillary and aggressive micropapillary features. Interestingly, RBM10 truncations were enriched in aggressive TMB LACD, seen in 2/2 cases of pleomorphic carcinoma and 4/7 cases with papillary or micropapillary features. BRAF class 2 mutations (non V600E) were also more likely to be seen in these aggressive tumors, identified in 5/33 cases of TMB high LADC, while no class 1 BRAF V600E mutations were observed. <h3>Conclusions</h3> A subset of high TMB LADC is especially aggressive, with histology including necrosis, micropapillary, and pleomorphic features. A subset of these tumors, with an especially poor overall survival rate contain either class 2 BRAF variants or truncated RBM10 mutations in 7/10 cases identified with these aggressive histologic features.

Value of Dual-Energy Computed Tomography for Detecting Small Pancreatic Ductal Adenocarcinoma.

The aim of the study is to evaluate the usefulness of virtual monoenergetic imaging (VMI) generated from dual-energy computed tomography (DECT) in detecting small pancreatic ductal adenocarcinomas (PDACs). This study included 82 patients pathologically diagnosed with small PDAC (≤30 mm) and 20 without pancreatic tumors who underwent triple-phase contrast-enhanced DECT. To assess diagnostic performance for small PDAC detection via a receiver operating characteristic analysis, 3 observers reviewed 2 image sets (conventional computed tomography [CT] set and combined image set [conventional CT + 40-keV VMI from DECT]). The tumor-to-pancreas contrast-to-noise ratio was compared between conventional CT and 40-keV VMI from DECT. The area under the receiver operating characteristic curve of the 3 observers were 0.97, 0.96, and 0.97 in conventional CT set and 0.99, 0.99, and 0.99 in combined image set (P = 0.017-0.028), respectively. The combined image set yielded a better sensitivity than the conventional CT set (P = 0.001-0.023), without a loss of specificity (all P > 0.999). The tumor-to-pancreas contrast-to-noise ratios of 40-keV VMI from DECT were approximately threefold higher than those of conventional CT at all phases. The addition of 40-keV VMI from DECT to conventional CT had better sensitivity for detecting small PDACs without compromising specificity.

Contribution of F-18 fluorodeoxyglucose PET/CT and contrast-enhanced thoracic CT texture analyses to the differentiation of benign and malignant mediastinal lymph nodes.

Texture analysis and machine learning methods are useful in distinguishing between benign and malignant tissues. To discriminate benign from malignant or metastatic mediastinal lymph nodes using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and contrast-enhanced computed tomography (CT) texture analyses with machine learning and determine lung cancer subtypes based on the analysis of lymph nodes. Suitable texture features were entered into the algorithms. Features that statistically significantly differed between the lymph nodes with small cell lung cancer (SCLC), adenocarcinoma (ADC), and squamous cell carcinoma (SCC) were determined. The most successful algorithms were decision tree with the sensitivity, specificity, and area under the curve (AUC) values of 89%, 50%, and 0.692, respectively, and naive Bayes (NB) with the sensitivity, specificity, and AUC values of 50%, 81%, and 0.756, respectively, for PET/CT, and NB with the sensitivity, specificity, and AUC values of 10%, 96%, and 0.515, respectively, and logistic regression with the sensitivity, specificity, and AUC values of 21%, 83%, and 0.631, respectively, for CT. In total, 13 features were able to differentiate SCLC and ADC, two features SCLC and SCC, and 33 features ADC and SCC lymph node metastases in PET/CT. One feature differed between SCLC and ADC metastases in CT. Texture analysis is beneficial to discriminate between benign and malignant lymph nodes and differentiate lung cancer subtypes based on the analysis of lymph nodes.

WHEN CANCERS COLLIDE: A COLLISION TUMOR OF ADENOCARCINOMA AND SMALL CELL CARCINOMA OF THE LUNGS

WHEN CANCERS COLLIDE: A COLLISION TUMOR OF ADENOCARCINOMA AND SMALL CELL CARCINOMA OF THE LUNGS

S1066 High 1-Year Survival Rate of UnresecTable Pancreatic Cancer Size Smaller Than 4 cm in Diameter Treated With Concurrent EUS-RFA: An Average Treatment Effect on the Treated Weighted Survival Analysis

Introduction: Treatment of small primary pancreatic ductal adenocarcinoma (PDAC), unresecTable due to of blood vessel involvement or distant metastasis, relies on systemic therapy only. We hypothesized that concurrent EUS-guided radiofrequency ablation (EUS-RFA) might control the primary tumor and improve patients’ outcomes. Methods: A prospective series of unresecTable PDAC patients with primary tumor size ≤4 cm who underwent EUS-RFA using a 19-gauge RFA needle (STARmed Koyang, Korea) from Jan 2017 – Jan 2022 were compared with matched historical controls. A propensity score was calculated using tumor size, staging, age adjusted Charleston Comorbidity Index (CCI), Chemotherapy regimen received, and interactions between CCI regimen and staging. This was used to reweight observations so covariate distribution in the chemotherapy only group equalled that of the RFA group (Average Treatment effect on the Treated weights). We used the VIVA combo RF system with an energy of 50 Watts and impedance of 100 Ohms. Chemotherapy was given if the patients were deemed tolerable by oncologists. The patients were followed for at least 12 months to see the survival rates. Results: 46 patients comprised of 11 patients in EUS-RFA group and 35 patients in control group were included in the analysis. The mean (SD) age was 63 (13.5) years in the RFA group and 68 (8.1) years in control group. Characteristics of patients, along with the standard mean differences before and after weighting are show in in Table. Median weighted survival was 14 months in the RFA group versus 6.1 months in the controls. The adjusted survival probability at 6 and 12 months was 73% and 64% in the EUS-RFA group, versus 69% and 17% in the controls. The hazard ratio (HR) for death was 0.38 (95%CI 0.17 to 0.84); p=0.016 in the RFA group versus the controls. Median weighted time to progression was 6.1 in the RFA group versus 3.9 months in the controls. The adjusted progression-free survival at 6 and 12 months in the EUS-RFA group were 55% and 36%, versus 28% and 4% in the controls; the HR for progression was 0.57 (95%CI 0.36 – 1.26); p = 0.16 in the RFA group versus controls. The adverse events were only mild abdominal pain which were observed in 8.3% of total RFA operations. Conclusion: In patients PDAC with primary lesions ≤4 cm that cannot be cured by surgery, EUS-RFA combined with chemotherapy resulted in improved survival and progression free survival with minimal adverse events.Figure 1.: Treatment outcomes compared RFA group with control group Table 1. - Baseline characteristics of the enrolled patients *Data are mean (SD) or n(%) as appropriate. Percentages are rounded to 1 decimal place and may not equal 100% Characteristic Raw (unweighted) After weighting Prospective cases (n=11) Historical controls (n=35) Prospective cases (n=11) Historical controls (n=35) Standardized mean difference p-value Mean age (years) 63 (13.5) 68 (8.1) Female sex, n(%) 9 (81.8) 22 (62.9) Mean CCI score 2.91 (2.4) 2.89 (1.3) 2.91 2.94 -0.055 0.98 Tumor diameter (cm) 3.25 (0.51) 3.10 (0.58) 3.25 3.25 0.008 0.90 Regimen, n(%) None 3 (27.3) 6 (17.1) 27.3 26.3 0.022 0.96 First-line 3 (27.3) 16 (45.7) 27.3 27.0 0.005 0.99 Second-line 5 (45.5) 13 (37.1) 45.5 46.7 -0.025 0.96 Staging Stage III 6 (54.6) 24 (68.6) 54.5 56.6 0.021 0.97 Stage IV 5 (45.5) 11 (31.4) 45.5 43.4 -0.021 0.97

Evaluation of thoracic diseases with computed tomography guided biopsy

Computed tomography (CT) guided percutaneous procedures like the fine needle aspiration cytology (FNAC) and fine needle aspiration biopsy (FNAB) are reliable techniques for diagnosing various thoracic diseases. These modalities are used for diagnosis in suspicious lung, pleural, mediastinal and vertebral and pulmonary lesions.The aim. We conducted a study in a Pulmonary Medicine Department of tertiary care hospital to study the efficacy and safety of CT guided FNCA/FNAB in thoracic diseases.Methods. A retrospective study was conducted at a tertiary care center with Information and Ethics committee permission within a total duration of two years. The study included patients presenting with following: 1) mediastinal mass lesions, 2) pulmonary solitary pulmonary nodules/masses, 3) pulmonary cavity, cyst and consolidation of undiagnosed etiology, 4) pleural mass, nodules, loculated collections, 5) extra-pulmonary and spinal tuberculosis suspects with pre/paravertebral abscess. Procedure details, radiological images and pathological and microbiological reports were retrieved from case record book of patients available in department.Results. Study population consisted of 108 patients. Neoplastic diseases were 85 (78.70%) and Non- neoplastic diseases 23 (21.29%). In neoplastic diseases 78.82% patients had lung Cancer of which 85.07% non small cell carcinoma and 14.92% small cell lung cancer. Out of non small cell lung cancer adenocarcinoma of lung was the commonest. The most common non neoplastic diseases was tuberculosis. CT guided biopsy procedure was performed without any complications in 61.11%. The most common complication was pneumothorax (27.77%). The yield of CT guided biopsy was 98.14%.Conclusion. Percutaneous CT-guided lung biopsy is an effective, highly accurate, and safe method of obtaining tissue for the diagnosis of indeterminate pulmonary lesions especially in neoplastic diseases and tuberculosis.

Aggressive histological component in subsolid lung adenocarcinoma: priority for resection without delay

This study explored the predictors of a histological aggressive component in ground glass opacity-containing lung adenocarcinoma. Of the 2388 patients who underwent resection for lung cancer at our institute between 2017 and 2020, we collected data on the 501 patients with ground glass opacity-containing adenocarcinoma with a total diameter of ≤2cm. Using a historical cohort, we identified histological aggressive components that were related to a poor prognosis in early-stage adenocarcinoma. A multivariable analysis was conducted to identify predictors for the presence of a histological aggressive component. Lymphovascular invasion and predominant micropapillary or solid patterns were identified as histological aggressive components by a prognostic analysis using a historical cohort. Of the 501 patients included, 36 (7.2%) had at least one histological aggressive component. A multivariate analysis showed that a consolidation/tumour ratio>0.5 (P<0.01), maximum standardized uptake value on positron emission tomography ≥1.5 (P=0.01) and smoking index >20 pack-years (P=0.01) were predictors of the presence of a histological aggressive component. A total of 98% of cases without any of the above factors did not have a histological aggressive component. Approximately 7% of ground glass opacity-containing small adenocarcinomas contained histological aggressive component. A consolidation/tumour ratio>0.5, maximum standardized uptake value≥1.5 and smoking index >20 pack-years were predictors for such cases. These predictors may be useful for screening patients with a potentially high risk of a poor prognosis and for prioritizing resection without delay.

One-step algorithm for fast-track localization and multi-category classification of histological subtypes in lung cancer

BackgroundsAccumulated evidence has proven that computer-derived features from computed tomography (CT) through radiomics and deep learning technologies can identify extensive characteristics of pulmonary malignancies, such as nodules detection and malignant lesion discrimination. However, there are few studies on whether CT images can reflect histological subtypes of lung cancer through computer-derived features. MethodsContrast-enhanced CT images prior treatment from 417 patients diagnosed with small cell lung cancer (SCLC), lung adenocarcinoma (ADC), or lung squamous cell carcinoma (SCC) were collected. ITK-SNAP software was used by trained radiologists for the manual delineation of tumor volume. Patients of each category (SCLC, ADC, SCC) were then randomly split into training datasets and test datasets in an approximately ratio of 8:2. After image pre-processing and augmentation, 25,042 CT images from the training datasets were used to train our self-developed deep learning model for fast-tracking tumor lesions and classifying corresponding histological subtypes simultaneously. The performance of the network was evaluated by accuracy, F1-score and weighted F1-average using 1,921 testing images based on parameters generated during training. ResultsThe prediction accuracy of SCLC, ADC, and SCC were 0.83, 0.75 and 0.67, respectively. The weighted F1-average was 0.75. ADC obtained the best F1-score of 0.78, which was outperformed SCLC (0.77) and SCC (0.66). The corresponding AUC values of SCLC, ADC, and SCC were 0.87, 0.84, and 0.76, respectively. Only 0.24 s were required to simultaneously achieve functions of tumor localization and histological classification on a thoracic CT image slice. The heat map visualization illustrated the extracted tumor features to classify subtypes of lung cancer by the proposed model. ConclusionsThe newly developed multi-task algorithm provides a CNN-based DL approach in lung cancer for automatically fast-tracking tumor lesions and classifying corresponding histological subtypes in one-step.

Histopathological Spectrum of Urinary Bladder Tumors: One Year Study in a Tertiary Health Care Centre

Introduction: This study was conducted to describe the Histopathological spectrum of various urinary bladder tumors and to classify them according to W.H.O(2004)/ISUP classification of urinary bladder tumors. Methods: This was a cross-sectional, observational study carried out between June 1, 2019 to May 31, 2020 for a period of one year in the Department of Pathology and Urology, Indira Gandhi Medical College, Shimla. One hundred and ninety seven patients (TURBT and radical cystectomy) with primary epithelial urinary bladder cancer were included in the study. However, Patients with inflammatory and metastatic lesions of urinary bladder and post chemoradiotherapy were excluded from the study. Results: The age of patients ranged from 36 to 89 years with mean age of 62 years. Male preponderance was observed with male to female ratio of 6.9:1. Most common histological type found in our study was urothelial carcinoma (98%) followed by other types such as Squamous cell carcinoma (1%), Small cell carcinoma (0.5%) and Adenocarcinoma (0.5%). In urothelial tumors (193), majority, 126(65.3%) cases, were high grade urothelial carcinoma followed by 67(34.7%) cases of low grade urothelial carcinoma. Conclusion: High grade urothelial carcinomas were mostly associated with muscularis propria invasion. Keywords: Urinary Bladder Tumors, Histopathological Spectrum, High grade urothelial carcinomas .