Histopathological Staging Research Articles

Application of cellular microstructural diffusion MRI (cell size imaging) in rectal lesions: a preliminary study

ObjectivesTo explore the value of cellular microstructural mapping by IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) method in evaluating the histological type and prognostic factors of rectal lesions.Materials and methodsSixty-six patients with rectal lesions were enrolled in this study. All subjects underwent MRI scans including conventional diffusion weighted imaging (DWI) and the IMPULSED MRI scans of oscillating gradient spin-echo (OGSE) and pulse gradient spin-echo (PGSE) sequences. Parameters including mean cell diameter (dmean), intracellular fraction (vin), extracellular diffusivity (dex), cellularity, and apparent diffusion coefficient (ADC) values (ADCPGSE, ADC17Hz, ADC33Hz, and ADC of conventional DWI) were measured in different histopathologic types, grades, stages, and structure invasion statuses. The receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic power. The sensitivity, specificity, and the corresponding area under the curves (AUCs) were calculated.ResultsOur preliminary results illustrated that malignant lesion showed higher vin and cellularity ([0.2867 ± 0.0697] vs. [0.1856 ± 0.1011], [2.3508 ± 0.6055] vs. [1.2716 ± 0.4574], all P<0.05), lower dex and ADC values (ADCPGSE, ADC17Hz, and ADC of conventional DWI) compared to benign lesion ([2.1637 ± 0.3303 μm2/ms] vs. [2.5595 ± 0.5085 μm2/ms], [0.9238 (0.7959, 1.0741) ×10-3 mm2/s] vs. [1.3373 ± 0.3902×10-3 mm2/s], [1.3204 ± 0.2342×10-3 mm2/s] vs. [1.8029 ± 0.3119×10-3 mm2/s], [0.7400 (0.6750, 0.8375) ×10-3 mm2/s] vs. [1.0550 ± 1.1191×10-3 mm2/s], all P<0.05), while no significant difference was seen for dmean. Vin and cellularity of rectal common adenocarcinoma (AC) were significantly higher than those of rectal mucinous adenocarcinoma (MC) ([0.2994 ± 0.0626] vs. [0.2028 ± 0.0571], [2.4579 ± 0.5553] vs. [1.6412 ± 0.4347], all P<0.05), while dex and ADC values (ADCPGSE, ADC17Hz, ADC33Hz, and ADC of conventional DWI) were lower in AC ([2.1189 ± 0.3187 μm2/ms] vs. [2.4609 ± 0.2534 μm2/ms], [0.8996 ± 0.1583×10-3 mm2/s] vs. [1.2072 ± 0.2326×10-3 mm2/s], [1.2714 ± 0.1916×10-3 mm2/s] vs. [1.6451 ± 0.2420×10-3 mm2/s], [1.8963 (1.6481, 2.1138) ×10-3 mm2/s] vs. [2.3104 ± 0.3851×10-3 mm2/s], [0.7341 ± 0.8872×10-3 mm2/s] vs. [1.1410 ± 0.1840×10-3 mm2/s], all P<0.05). In AC group, the dmean had significant difference between negative and positive tumor budding (TB) ([13.2590 ± 1.3255 μm] vs. [14.3014 ± 1.1830 μm], P<0.05). No significant difference of dmean, vin, dex, cellularity or ADC values was observed in AC with different grade, T stage, N stage, perineural and lymphovascular invasion (all P>0.05). The ROC curves showed that the area under the curves (AUCs) of vin, dex, cellularity, and ADC values (ADCPGSE, ADC17Hz, and ADC of conventional DWI) for distinguishing malignant and benign lesion were 0.803, 0.757, 0.948, 0.807, 0.908 and 0.905, respectively. The AUCs of vin, dex, cellularity, and ADC values (ADCPGSE, ADC17Hz, ADC33Hz, and ADC of conventional DWI) in distinguishing AC from MC were 0.887, 0.802, 0.906, 0.896, 0.896, 0.781 and 0.991, respectively. The AUC of the dmean for evaluating TB status was 0.726. The AUC of ADC from conventional DWI for evaluating WHO grade was 0.739.ConclusionCellular microstructural mapping by the IMPULSED method has great potential in preoperative evaluation of rectal lesions. It could be helpful in differentiating malignant and benign lesions, distinguishing AC from MC, and in predicting the TB status.

Usefulness of multiparametric MRI for local staging of bladder cancer

Introduction: Under staging and over staging are not uncommon with traditional MRI while staging bladder cancer. Current improvements in MRI technology due to addition of functional MR sequences that is, dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI) have enhanced its clinical utility. The current study was designed to look for staging accuracy of multiparametric MRI (mp-MRI) that is, T2W + DCE + DWI, over conventional MRI. Material and methods: Forty patients with bladder cancer were included were subjected to mp-MRI on a 3T scanner with a phased array body coil. Four MR image sets that is, T2W, T2W + DCE, T2W + DWI, and T2W + DCE + DWI were interpreted. Accuracy of each image set was determined separately and was compared with the gold standard histopathological staging. Result: Staging accuracy of different image set increased from T2W (55%) to DCE (72.5%) to DWI (80%). Maximum accuracy was seen in mp-MRI (T2W + DWI + DCE) (87.5%). While differentiating non muscle invasive from muscle invasive disease (⩽T1 vs ⩾T2 stage) staging accuracy increased from T2W (65%) to DCE (80%) to DWI (85%) with maximum in mp-MRI (90%). Conclusion: mp-MRI offers high staging accuracy for bladder cancer.

Utility of Serum Lipids and CEA Levels as Novel Markers in Comparison to Various Histopathological Parameters and TNM Staging in Colorectal Carcinoma: A Research Protocol

Introduction: Colorectal Cancer (CRC) is the third most widespread type of cancer around the globe. Elevated Carcinoembryonic Antigen (CEA) levels, a blood protein, are often observed in CRC patients. Need of the Study: Among gastrointestinal cancers, CRC is the most frequent cause of death. This research aims to investigate the potential link between serum lipid profiles, the levels of CEA, and the risk of developing CRC. Early detection and staging of CRC are crucial for effective management and improved outcomes. Aim: To evaluate the efficacy of serum lipids and CEA levels as novel markers compared to different Tumour Node Metastasis (TNM) staging and histopathological parameters in CRC. Materials and Methods: A cross-sectional study will be conducted in the Department of Pathology at Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Sawangi, Wardha, Maharashtra, India from October 2024 to April 2026. Peripheral blood samples will be collected from CRC patients to determine serum lipid profiles and CEA levels. Resected colon specimens will be processed and graded using TNM staging with appropriate staining. Karl Pearson’s test (data distributed normally) or Spearman’s test (data distributed non normally) will be used to conduct a correlation between continuous variables. A p-value of less than 0.05 will be considered statistically significant.

68Ga-Prostate-Specific Membrane Antigen PET/CT in Endometrial Cancer: A Preliminary Report.

Endometrial cancer is the most common gynecological cancer. Prostate-specific membrane antigen (PSMA) is expressed in prostate cancer cells but can be found in other cancers, such as endometrial cancer, during angiogenesis.The aim of this prospective pilot study was to evaluate the feasibility of using 68Ga-PSMA-11 PET/CT in endometrial cancer patients before surgical treatment. Seven women with a mean age of 58 ± 7.9 years were included in the study. All patients underwent standard imaging studies involving transvaginal ultrasound, ceCT scans of the chest and abdomen, and MRI as qualified for surgery. Additionally, PET/CT was performed on a Siemens Biograph scanner 60 minutes after the injection of 2 MBq/kg 68Ga-PSMA-11. Six of 7 patients had positive 68Ga-PSMA-11 PET/CT images, and histopathology confirmed endometrial cancer. One patient also exhibited uptake in the left ovary, and final histopathology revealed a hemorrhagic cyst. Lymph node involvement was further confirmed after ceCT fusion with 68Ga-PSMA-11. The consensus of histopathological staging of endometrial cancer and ceCT was 4/7, that of MR was 6/7, and that of 68Ga-PSMA-11 PET/CT was 5/7. All methods were consistent in terms of staging in 3/7 patients. The initial experience showed the possibility of using 68Ga-PSMA-11 in endometrial cancer patients. However, prospective large studies are needed to explore the real diagnostic role of radiolabelled PSMA in this field.This study was approved by the Ethical Committee of the Medical University of Warsaw (KB/2/A/2018).

Histopathological Features and Diagnosis of Breast Cancer

In Indonesia, the high number of breast cancer cases is not always followed by complete clinical and histopathological determination, even though clinical and histopathological staging is needed to determine the diagnosis and further management. Breast cancer is a malignant mass originates from the uncontrolled division of cells in breast tissue Breast cancer or mammary carcinoma is a lump that grows and develops abnormally in the cells and tissues located in the breast, such as the fat tissue and connective tissue in the breast, ducts and lobules. The histopathological examination procedure is that the patient must undergo a biopsy. Biopsy results can be used to diagnose breast cancer and also monitor the success of therapy. Mammary carcinoma can spread to surrounding tissue or to other organs through blood vessels. Breast cancer is the most common cancer in Indonesia. The prognosis of breast cancer is determined by the 5 years survival rate. The survival rate for cancer sufferers in Indonesia is low compared to other developing countries, namely 51.07%. This research is in the form of a literature review with 14 papers as references. The results obtained were that invasive ductal carcinoma was the most common mammary carcinoma and grade II-III was found to be the dominant grade.

Impact of COVID-19 Pandemic on Delay of Melanoma Diagnosis: A Systematic Review and Meta-Analysis.

Several studies have described how the restrictive measures due to COVID-19 have delayed melanoma diagnoses, resulting in an increased rate of more severe cases. Summarizing the sparse results in this context might help to understand the real impact of the COVID-19 pandemic on melanoma. We conducted a systematic review and meta-analysis to investigate how the clinical and prognostic factors of new melanoma diagnoses changed after COVID-19. A literature search in MEDLINE, EMBASE, and Scopus was conducted in September 2023. We included studies published in peer-reviewed journals reporting histopathological data on new diagnoses of cutaneous melanoma in adult patients during and/or after the lockdown compared to those diagnosed before the COVID-19 pandemic. A meta-analysis was conducted utilizing a random effects model. The between-study heterogeneity was assessed via Higgins's I2 statistic. Publication bias was assessed using the Begg and Egger test. This study adhered to the updated PRISMA guidelines. The primary outcome was a comparison of melanoma thickness between the pre-COVID-19 and post-lockdown periods. The secondary outcomes were evaluations of the histopathological subtype, stage, and presence of ulceration and mitosis in melanomas diagnosed in these two pandemic phases. The study included 45 articles. We found a significantly higher proportion of all factors indicating worse prognosis in the post-lockdown period compared to the pre-COVID-19 phase, including high thickness (SOR = 1.14, 95%CI 1.08-1.20 for 1-2 mm; SOR = 1.62, 95%CI 1.08-2.40, for >2 mm), the presence of ulcerations (SOR = 1.35, 95%CI 1.18-1.54), nodular subtype (SOR = 1.19, 95%CI 1.07-1.32), the presence of mitosis (SOR = 1.57, 95% CI 1.17-2.11), and stage III (SOR = 1.39, 95%CI 1.19-1.52) and IV (SOR = 1.44, 95%CI 1.26-1.63). Limitations include the limited studies' geographical distribution and moderate heterogeneity affecting meta-analysis estimates. Our meta-analysis provided evidence of more advanced melanomas diagnosed in the post-COVID-19 pandemic period, emphasizing the importance of creating and updating pandemic preparedness plans to limit the impact of any future events on oncological care.

The oncogenic functions of SPARCL1 in bladder cancer.

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) belongs to the SPARC family of matricellular proteins. However, underlying functions of SPARCL1 in bladder cancer (BCa) remain understudied. We performed an integrated search for the expression patterns of SPARCL1 in relation to various clinicopathological features of BCa. We then carried out Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA). Furthermore, we investigated the correlations between SPARCL1 and immunological features, such as tumour mutation burden (TMB), immune activation processes, immune checkpoint expression, tumour immune dysfunction and exclusion (TIDE) scores, and chemotherapeutic sensitivity in BCa. Our analysis revealed that SPARCL1 was downregulated across multiple cancers. In BCa, elevated SPARCL1 was linked with advanced histopathologic stage, higher T and N stage, and poorer prognosis in the clinical cohort. Invitro experiments demonstrated that increased SPARCL1 expression inhibited cell proliferation, migration, and invasion. Additionally, highly expressed SPARCL1 was linked to elevated immune, stromal and ESTIMATE scores, as well as an increase in naive B cells, M2 macrophages, and resting mast cells. We observed a moderate correlation between SPARCL1 expression and CD163, VSIG4 and MS4A4A, which are markers of M2 macrophages. Furthermore, SPARCL1 expression was positively related to TMB, immune activation processes, TIDE scores, immune checkpoint expression, and chemotherapeutic sensitivity in BCa. Our study highlights the potential involvement of SPARCL1 in macrophage recruitment and polarization and suggests its utility as a biomarker for prognosis in BCa.

Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors

The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms. We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts). The ICI benefit group was enriched for propionate (P=0.01) and butyrate/isobutyrate (P=0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P<0.001, butyrate/isobutyrate P=0.002). The acetyl-CoA pathway (P=0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P=0.07), which was validated in the Routy cohort (P=0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P=0.03), propionic acid (P=0.09), and butyric acid (P=0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P<0.05). Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088). This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).

Role of artificial intelligence in staging and assessing of treatment response in MASH patients.

The risk of disease progression in MASH increases proportionally to the pathological stage of fibrosis. This latter is evaluated through a semi-quantitative process, which has limited sensitivity in reflecting changes in disease or response to treatment. This study aims to test the clinical impact of Artificial Intelligence (AI) in characterizing liver fibrosis in MASH patients. The study included 60 patients with clinical pathological diagnosis of MASH. Among these, 17 received a medical treatment and underwent a post-treatment biopsy. For each biopsy (n = 77) a Sirius Red digital slide (SR-WSI) was obtained. AI extracts >30 features from SR-WSI, including estimated collagen area (ECA) and entropy of collagen (EnC). AI highlighted that different histopathological stages are associated with progressive and significant increase of ECA (F2: 2.6% ± 0.4; F3: 5.7% ± 0.4; F4: 10.9% ± 0.8; p: 0.0001) and EnC (F2: 0.96 ± 0.05; F3: 1.24 ± 0.06; F4: 1.80 ± 0.11, p: 0.0001); disclosed the heterogeneity of fibrosis among pathological homogenous cases; revealed post treatment fibrosis modification in 76% of the cases (vs 56% detected by histopathology). AI characterizes the fibrosis process by its true, continuous, and non-categorical nature, thus allowing for better identification of the response to anti-MASH treatment.

Evaluation of the role of EGFR exon 19 747-750 deletion mutation and plasma amino acid profile in the development of lung cancer.

Lung cancer (LC) is the most common form of cancer in the world. Of the proteins involved in cell differentiation and proliferation, the epidermal growth factor receptor (EGFR) is among the most significant. Amino acids play a crucial role in cell physiology as metabolic regulators. The benefits of liquid biopsies are their non-invasive nature, ease of collection, and ability to depict the entire tumor's status. The present study is designed to detect the relation between the EGFR exon 19 747-750 deletion mutation and lung cancer and investigate the patterns of alterations of plasma-free amino acids (PFAA) in lung cancer patients of different histopathological types and stages as biomarkers for early detection of lung cancer. The study sample comprised 60 lung cancer patients and 60 age- and sex-matched healthy individuals as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the EGFR exon 19 747-750 deletion mutation, and an AA analyzer was used to quantify the plasma free amino acid (PFAA) profile. Compared with controls, LC patients had significantly higher levels of three AAs and significantly lower levels of fifteen AAs. Thirteen AAs varied significantly between stages I and II. In the lung cancer group, the percentage of cases of mutant EGFR exon-19 deletion increased to 30% from 13.3% in the control group. The histological forms of lung cancer did not significantly differ in this rise. Valine and citrulline plasma levels were substantially greater in the mutant than in the wild-type. Lysine, histidine, and methionine were the independent predictors of the LC group in multivariate analysis. Lung cancer development is influenced by the EGFR exon 19 747-750 deletion mutation, and the prognosis and early prediction of lung cancer are greatly affected by the amino acid profile concentrations.

Distinguishing of Histopathological Staging Features of H-E Stained Human cSCC by Microscopical Multispectral Imaging.

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignant skin tumor. Early and precise diagnosis of tumor staging is crucial for long-term outcomes. While pathological diagnosis has traditionally served as the gold standard, the assessment of differentiation levels heavily depends on subjective judgments. Therefore, how to improve the diagnosis accuracy and objectivity of pathologists has become an urgent problem to be solved. We used multispectral imaging (MSI) to enhance tumor classification. The hematoxylin and eosin (H&E) stained cSCC slides were from Shanghai Ruijin Hospital. Scale-invariant feature transform was applied to multispectral images for image stitching, while the adaptive threshold segmentation method and random forest segmentation method were used for image segmentation, respectively. Synthetic pseudo-color images effectively highlight tissue differences. Quantitative analysis confirms significant variation in the nuclear area between normal and cSCC tissues (p < 0.001), supported by an AUC of 1 in ROC analysis. The AUC within cSCC tissues is 0.57. Further study shows higher nuclear atypia in poorly differentiated cSCC tissues compared to well-differentiated cSCC (p < 0.001), also with an AUC of 1. Lastly, well differentiated cSCC tissues show more and larger keratin pearls. These results have shown that combined MSI with imaging processing techniques will improve H&E stained human cSCC diagnosis accuracy, and it will be well utilized to distinguish histopathological staging features.

The added value of 68Ga-PSMA PET/CT in anatomical staging of prostatic carcinoma in correlation with the histopathological zonal staging

BackgroundProstate cancer is well known as the commonest cancer in men and the second leading cause of cancer-related death. CT, MRI and bone scintigraphy are considered the commonly widely used imaging diagnostic tools for detection, staging and follow-up of prostate cancer. Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, that can be concentrated in prostate cancer cells up to 100 times higher than in normal cells. PSMA-targeted imaging modalities have now proven their efficacy in diagnosis, staging and follow-up of prostate cancer. The use of 68Ga PSMA PET-CT has efficiently improved the detection of loco-regional and metastatic disease. 68Ga PSMA PET-CT also has an effective role in the primary diagnosis, staging, and detecting biochemical recurrence after curative treatment and in metastasis-targeted therapy. This work aims to review the role of 68Ga PSMA PET-CT in anatomical staging of prostate cancer in correlation with histopathological staging.ResultsZonal correlation between 68Ga PSMA findings and biopsy results showed sensitivity ranging between 76.9 and 90.6% and specificity ranging from 85.7 to 100%. There was high significant correlation between the SUVmax uptake and the biopsy results, between the SUVmax uptake and the local staging as well as between the Gleason score and 68Ga PSMA PET/CT findings.Conclusions68Ga PSMA PET/CT is a highly promising imaging modality with an effective role in detection of prostate cancer showing high sensitivity and specificity in prediction of zonal histopathological results and loco-regional Gleason score staging with significant positive correlation between the SUV uptake results, Gleason score and the PSA levels.

Correlation of preoperative sonographic staging and postoperative histopathologic staging in patients with invasive breast cancer.

To assess the accuracy of preoperative sonographic staging in patients with primary invasive breast cancer. We retrospectively analyzed a prospectively kept service database of patients with newly diagnosed, unifocal, cT1-3, invasive breast cancer. All patients were diagnosed at a single center institution between January 2013 and December 2021. Clinical T stage was assessed preoperatively by ultrasound and correlated with the definite postoperative pathologic T stage. Demographics, clinical and pathological characteristics were collected. Factors influencing accuracy, over- and underdiagnosis of sonographic staging were analyzed with multivariable regression analysis. A total of 2478 patients were included in the analysis. Median patients' age was 65years. 1577 patients (63.6%) had clinical T1 stage, 864 (34.9%) T2 and 37 (1.5%) T3 stage. The overall accuracy of sonography and histology was 76.5% (n = 1896), overestimation was observed in 9.1% (n = 225) of all cases, while underestimation occurred in 14.4% (n = 357) of all cases. Accuracy increased when clinical tumor stage cT was higher (OR 1.23; 95% CI 1.10-1.38, p ≤ 0.001). The highest accuracy was seen for patients with T2 stage (82.8%). The accuracy was lower in Luminal B tumors compared to Luminal A tumors (OR 0.71; 95% CI 0.59-0.87, p ≤ 0.001). We could not find any association between sonographic accuracy in HER2 positive patients, and demographic characteristics, or tumor-related factors. Our unicentric study showed a high accuracy of sonography in predicting T stage, especially for tumors with clinical T2 stage. Tumor stage and biological tumor factors do affect the accuracy of sonographic staging.

Study of histopathological and ultrastructural changes in the lungs of COVID-19 patients

BackgroundCOVID 19 infection is a multi-systemic disease with the lungs bearing the maximum brunt. Very few autopsy studies have been done on the deceased patients. The present study aimed to study the clinical spectrum and lab parameters of COVID-19 patients along with the morphological spectrum of the lung changes in these patients by histology, Immunohistochemistry and Electron microscopy. We also compared the Clinical severity and Lab parameters with the histopathological phase of the lung involvement. MethodsWe conducted a cross sectional observational study between Jun 2021 to Dec 2022 where in needle necropsy of lung tissue of COVID 19 confirmed fatal cases were studied by histopathology, immunohistochemistry (using CD3, CD4, CD8, CD19, CD20, CD68 and Pan CK markers) and Electron microscopy. Various hematological, histopathological and ultrastructural parameters were studied. The results were analyzed using SPSS 25.0 software. ResultsA total of 24 cases were studied. The mean age was 65.9 yrs, male: female ratio was 2:1. Five had moderately severe COVID while 19 had severe COVID infection. Diffuse alveolar damage (DAD) was seen in 83% of all the cases. On the basis of clinical severity and histopathological staging, broadly two histopathological groups were made (Proliferative and Organizing). Difference between TLC, N/L ratio and L/Platelet ratio in two histopathological groups was assessed using unpaired t test, however no significant difference was noted. We did not find any correlation between clinical severity and histopathological groups though severe cases of COVID-19 were found to have a shorter time between admission to the hospital and death. All the biopsies were subjected to electron microscopy and in two of the cases we could demonstrate corona virus particles. ConclusionOur study has shown that severe cases of COVID 19 are associated with a shorter time between admission to hospital and death. While the histopathology of the lung showed diffuse alveolar damage as the most common finding; the Transmission Electron Microscopy (TEM) played an important role in characterizing the ultrastructure of these cells and demonstrating corona virus particles.

637. UPFRONT SURGERY IN ESOPHAGEAL CANCER: ACCURACY OF PREOPERATIVE CLINICAL STAGING

Abstract Background Treatment of locally limited esophageal cancer is still a frequently discussed topic. Especially, the inaccuracy of clinical staging in lymph node-negative T2-carcinomas has to be considered further in the treatment pathway. Aim of this study was to evaluate the accuracy of clinical staging in patients treated with esophagectomy without neoadjuvant treatment. Methods We conducted a retrospective multicenter analysis at the departments of surgery from two university clinics. All patients between January 2016 and December 2023, who underwent an esophagectomy because of an esophageal adenocarcinoma or squamous cell carcinoma without neoadjuvant treatment were included. Advanced tumor stage, T staging greater than T2, was defined as exclusion criteria. Results Fifty-three patients after upfront esophagectomy were included in the analysis. In 40 (75%) patients a gastroesophageal junction adenocarcinoma was diagnosed, and 13 (25%) patients were treated because of a squamous cell carcinoma of the esophagus. Clinical T staging was T1 or T2 and all lymph node stages were included. The endosonographic preoperative staging of invasion depth was accurate in 32 (60%) patients in comparison to the histopathological staging. In 7 (13%) cases the T-values were upstaged one level and in 5 (9%) cases one level downstaged after resection. The endosonographic preoperative staging of nodal spread was accurate in 32 (60%) patients. Furthermore, in 7 (13%) cases node status was upstaged and in 5 (9%) patients downstaged. Nine (17%) patients did not undergo a sufficient endosonographic staging, mainly due to prior endoscopic submucosal dissection or stenosis. In these patients, clinical lymph node staging was accurate in 4 patients. Conclusion Preoperative staging using endoscopic ultrasound and computed tomography is not accurate enough in a high number of patients, therefore we are seeking to identify other predictive factors underlying advanced stage esophageal cancer.

Distribution Patterns of Morphologies of Colorectal Carcinoma: A Descriptive, Cross-Sectional Study

Background: Colorectal malignancies are one of the commonest cancers throughout the world which is often diagnosed at advanced stages. Several lifestyle factors contribute to the development of this cancer such as a high intake of processed meats and low intake of fruits and vegetables, sedentary lifestyle, obesity, smoking and excessive alcohol consumption. Methods: This cross-sectional study was conducted in BIRDEM General Hospital in Dhaka in the Department of Pathology with 109 resected colectomy specimens during the period of March 2020 to February 2022. Relevant findings were recorded and analyzed for determining the morphological characteristics based on histopathological types, grading and staging of the malignancy. Results: Maximum patients belonged to 51-60 years of age; were males, hailing from urban regions and found to indulge in smoking. Per rectal bleeding, alteration of bowel habits and abdominal pain were the most frequently reported clinical symptoms. The commonest areas of occurrence of the tumors were rectum, recto-sigmoid junction and caecum. Out of all the 109 cases, 48, 45 and 16 belonged to non-mucinous, mucinous and signet-ring types as per histological classification respectively. Among these, 39 of non-mucinous and 24 of mucinous types belonged to Dukes’ B staging whereas 11 of the signet-ring variants fell in Dukes’ C stage. Regarding grading, maximum patients, meaning 68 out of 109, belonged to Grade II. After performing Fisher’s exact test, associations between staging and grading, grading and types and types and grading were found statistically significant. Conclusion: Colon and rectal mucin-secreting and signet-ring cell adenocarcinomas are high grade cancers that usually show up at an advanced stage.

Targeted gene sequencing reveals disparate genomic mutations between young and older adults in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated.MethodsClinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator.ResultsOur analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs.ConclusionOur findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Can the Briganti 2019 nomogram be modified to predict lymph node metastasis risk in patients with prostate cancer detected with in-bore biopsy?

We aimed to modify the Briganti 2019 nomogram and to test whether it is valid for patients who were diagnosed with prostate cancer through in-bore prostate biopsies. Data for 204 patients with positive multiparametric prostate MRI and prostate cancer identified either by mpMRI-cognitive/software fusion or in-bore biopsy and who underwent robot-assisted radical prostatectomy and extended pelvic lymph node dissection between 2012 and 2023 were retrospectively analyzed. The Briganti 2019 nomogram was applied to the mpMRI-cognitive/software fusion biopsy group (142 patients) in the original form, and then, two modifications were tested for the targeted component. Original and modified scores were compared. These modifications were adapted for the in-bore biopsy group (62 patients). The final histopathologic stage was regarded as the gold standard. Nodal metastases were identified in 18/142 (12.6%) of mpMRI-cognitive/software fusion biopsy patients and 8/62 (12.9%) of the in-bore biopsy patients. In the mpMRI-cognitive/software fusion biopsy group, tumor size/core size (%) of targeted biopsy cores and positive core percentage on systematic biopsy were significant parameters for lymph node metastasis based on univariate logistic regression analyses (p < 0.05). With the modifications of these parameters for the in-bore biopsy group, V1 modification of the Briganti 2019 nomogram provided 100% sensitivity and 31.5% specificity (AUC:0.627), while V2 modification provided 75% sensitivity and 46.3% specificity (AUC:0.645). Briganti 2019 nomogram may be modified by utilizing tumor size/core size (%) for targeted biopsy cores instead of positive core percentage on systematic biopsy or by not taking both parameters into consideration to detect node metastasis risk of patients diagnosed with in-bore biopsies.

Dynamics of the thymic transcriptome at stages of acute thymic involution in Japanese Black calves with a poor prognosis

Transcriptome analysis was performed on the thymus of Japanese Black calves that were necropsied due to poor prognosis, to characterize changes associated with acute thymic involution. Gene expression profiles obtained by DNA microarray analysis of eight calf thymuses were classified into three patterns that correlated with the histopathological stage of acute thymic involution. Using principal component analysis, the first principal component of the global gene expression levels in the calf thymus was associated with the stage of acute thymic involution, suggesting that histopathological changes greatly influence the gene expression profile. Gene ontology enrichment analysis revealed that genes related to cell proliferation, wound healing, and inflammatory responses were the main contributors to the first principal component. Real-time RT-PCR showed that the thymus had lower expression of PCNA, KIFC1, and HES6, and higher expression of SYNPO2, PDGFRB, and TWIST1 during acute thymic involution. Immunohistochemistry demonstrated a decrease in the rate of Ki67-positive cells in the thymic cortex during the late stage of acute thymic involution. The rate of cleaved caspase-1-positive cells increased in the thymic cortex at an earlier stage than the increase in the rate of cleaved caspase-3-positive cells. Vimentin, which was almost absent in the non-involuted thymic cortex, appeared in the thymic cortex during acute thymic involution. These results suggest that in farmed calves with a poor prognosis, inflammatory responses and impaired thymocyte proliferation are primarily involved in acute thymic involution.

Advancing Tau PET Quantification in Alzheimer Disease with Machine Learning: Introducing THETA, a Novel Tau Summary Measure.

Alzheimer disease (AD) exhibits spatially heterogeneous 3- or 4-repeat tau deposition across participants. Our overall goal was to develop an automated method to quantify the heterogeneous burden of tau deposition into a single number that would be clinically useful. Methods: We used tau PET scans from 3 independent cohorts: the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center (Mayo, n = 1,290), the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 831), and the Open Access Series of Imaging Studies (OASIS-3, n = 430). A machine learning binary classification model was trained on Mayo data and validated on ADNI and OASIS-3 with the goal of predicting visual tau positivity (as determined by 3 raters following Food and Drug Administration criteria for 18F-flortaucipir). The machine learning model used region-specific SUV ratios scaled to cerebellar crus uptake. We estimated feature contributions based on an artificial intelligence-explainable method (Shapley additive explanations) and formulated a global tau summary measure, Tau Heterogeneity Evaluation in Alzheimer's Disease (THETA) score, using SUV ratios and Shapley additive explanations for each participant. We compared the performance of THETA with that of commonly used meta-regions of interest (ROIs) using the Mini-Mental State Examination, the Clinical Dementia Rating-Sum of Boxes, clinical diagnosis, and histopathologic staging. Results: The model achieved a balanced accuracy of 95% on the Mayo test set and at least 87% on the validation sets. It classified tau-positive and -negative participants with an AUC of 1.00, 0.96, and 0.94 on the Mayo, ADNI, and OASIS-3 cohorts, respectively. Across all cohorts, THETA showed a better correlation with the Mini-Mental State Examination and the Clinical Dementia Rating-Sum of Boxes (ρ ≥ 0.45, P < 0.05) than did meta-ROIs (ρ < 0.44, P < 0.05) and discriminated between participants who were cognitively unimpaired and those who had mild cognitive impairment with an effect size of 10.09, compared with an effect size of 3.08 for meta-ROIs. Conclusion: Our proposed approach identifies positive tau PET scans and provides a quantitative summary measure, THETA, that effectively captures heterogeneous tau deposition observed in AD. The application of THETA for quantifying tau PET in AD exhibits great potential.