Histopathological Data Research Articles

Clinicopathological and molecular markers for the identification of Hashimoto’s thyroiditis as a possible predisposing and prognostic factor of papillary thyroid carcinoma

Background: The papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, while Hashimoto’s thyroiditis (HT) is the most common inflam¬matory thyroid disease. The coincidental coexistence or the possible predisposing, protective or aggravating role of HT in the development of PTC have been repeatedly examined. Aim: The aim of the present study was to eval¬uate histopathological and clinical data obtained from pa¬tients with HT, PTC, and PTC+HT so as to investigate the possible association of HT with PTC. Methodology: The study’s cohort consisted of 114 patients (67 PTC, 29 PTC+HT, and 18 HT patients). A full record of their clini¬copathological and clinical laboratory data was followed by extensive statistical analysis in order to reveal possi¬ble correlations between the existence of each disease and various clinicopathological parameters. The study was conducted from 2019 to 2023 at the Hippokration General Hospital of Athens (Greece). Results: A signifi¬cant increase in the levels of thyroid-stimulating hormone (TSH; p=0.031), anti-thyroglobulin antibodies (Anti-Tg; p<0.001), and anti-thyroid peroxidase antibodies (Anti-TPO; p<0.001) was observed in the PTC+HT group. These patients also have smaller tumors (p=0.015) and a younger age of disease onset (p<0.001), while the ma¬jority of PTC+HT patients were women (p=0.023) and had infiltrated lymph nodes (p=0.002). Furthermore, the majority of patients with infiltration of the capsule be¬longed to the PTC+HT group (57.1%; p=0.032). Conclu¬sion: PTC+HT represents a less aggressive clinical state, as good prognostic markers of PTC correlate with the presence of HT. In PTC+HT patients, the PTC tends to have early onset age and the primary tumor is often small, while the majority of PTC+HT patients are women.

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

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Targeted Therapy in Salivary Gland Cancer: Prevalence of a Selected Panel of Actionable Molecular Alterations in a German Tertiary Referral Center Patient Cohort.

Salivary gland carcinomas (SGC) are a heterogeneous group of malignancies, with 24 subtypes defined by the World Health Organization (WHO). The standard of therapy is surgical resection, with adjuvant radiotherapy in most cases. However, disease recurrence (R) or metastasis (M) is common and no active systemic therapies are currently available for RM-SGC resulting in a 5-year survival rate of only 20%. Overall, 55 SGC patients with seven different histological tumor subtypes were included in this study. formalin-fixed paraffin-embedded (FFPE) tissue samples were used for immunohistochemical (IHC) staining targeting HER2/neu, androgen receptor (AR), PD-L1, EGFR, panTRK, and TROP2. Fluorescence in situ hybridization (FISH) was performed for detecting HER2/neu amplifications and NTRK1/2/3 translocations in selected cases with relevant HER2/neu and panTRK protein expression, respectively. IHC and FISH results were correlated with patients' clinical and histopathological data. The overall prevalence of druggable molecular alterations, defined as an immunoreactive score ≥ 9 in at least one of the analyzed targets, was 54.4% with the highest percentage in oncocytic carcinomas (100%) and lowest percentage in acinic cell carcinomas (10%). EGFR overexpression proved to be the most common alteration (32.7% of cases) followed by overexpression of TROP2 (27.3%), AR (10.9%), HER2/neu (7.3%), PD-L1 (1.8%), and panTRK (1.8%). HER2/neu amplifications were found in 50% and NTRK translocations were found in 100% of all cases with elevated Her2/neu and panTRK protein expression, respectively. Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.

Lupus anticoagulant-hypoprothrombinemia syndrome with lupus nephritis in a girl misdiagnosed with immunoglobulin A nephropathy: a case report

Distinguishing lupus nephritis (LN) from other glomerulopathies, such as immunoglobulin A nephropathy (IgAN), poses a diagnostic challenge owing to overlapping clinical and histopathologic findings. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare and potentially fatal disorder characterized by the presence of lupus anticoagulant and acquired factor II deficiency. We report a pediatric case of LN with LAHPS, which was initially diagnosed as IgAN. An 8-year-old girl presented with gross hematuria with nephrotic syndrome. Based on the kidney biopsy results, treatment for IgAN with membranoproliferative pattern was initiated. Two months later, she developed left upper extremity swelling with multiple vein thromboses requiring anticoagulation; treatment led to remission, allowing discontinuation of immunosuppressants within 8 months. Gross hematuria recurred 10 months later and was accompanied by hypocomplementemia; positive antinuclear, anti-double stranded DNA, and triple antiphospholipid antibodies; and factor II deficiency, prompting revision of the diagnosis to LN and LAHPS. Initial delay in LN diagnosis was attributed to the patient’s young age, nonspecific symptoms, and inconclusive laboratory and histopathological findings. Immunosuppressive therapy for IgAN partially improved LN, further complicating the diagnosis. This case emphasized the importance of clinical suspicion; integrating clinical, serological, and histopathological data; and considering LAHPS in differential diagnosis of glomerulonephritis with coagulopathy.

PSMA PET/CT Accuracy in Diagnosing Prostate Cancer Nodes Metastases.

This study aimed to evaluate the diagnostic accuracy of prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) in pelvic nodal staging, using postoperative histopathology data as the reference standard. From January 2020 to June 2024, 78 patients with clinically significant prostate cancer (PCa) (ISUP Grade Group 2) underwent radical prostatectomy plus extended pelvic lymph node dissection (ePLND): 60 (77%) vs. 18 (23%) men had an intermediate vs. high risk PCa. All the patients underwent PSMA PET/TC before surgery for clinical staging and nodes focal uptake (standardized uptake value "SUVmax) was evaluated to rule out the presence of metastases. PSMA PET/CT was suspicious for nodes metastases in 16/78 (20.5%) men (median SUVmax 26.2), conversely, histology demonstrated nodes metastases in 18/78 (23.1%). PSMA PET/CT was negative for nodal involvement in all Grade Group 2 (GG2) PCa, positive in 4/4 (100%) GG3 PCa, and in 10/14 (71.4%) GG5 PCa. In detail, PSMA PET/CT was false negative in 2/4 PCa, characterized by GG5 plus ductal adenocarcinoma. Overall, PSMA PET/CT sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy in diagnosing nodal metastases were equal to 87.5, 96.8, 87.5 96.7, and 92.3%, respectively. PSMA PET/CT demonstrated an overall diagnostic accuracy of 92.3% in nodal staging (100% in GG2 PCa), which decreased to 63.6% in GG5 PCa. In high-risk patients or in case of ductal adenocarcinoma, a negative PSMA PET/CT does not rule out the need for ePLND.

Evaluating the performance of multi-omics integration: a thyroid toxicity case study.

Multi-omics data integration has been repeatedly discussed as the way forward to more comprehensively cover the molecular responses of cells or organisms to chemical exposure in systems toxicology and regulatory risk assessment. In Canzler etal. (Arch Toxicol 94(2):371-388. https://doi.org/10.1007/s00204-020-02656-y ), we reviewed the state of the art in applying multi-omics approaches in toxicological research and chemical risk assessment. We developed best practices for the experimental design of multi-omics studies, omics data acquisition, and subsequent omics data integration. We found that multi-omics data sets for toxicological research questions were generally rare, with no datasets comprising more than two omics layers adhering to these best practices. Due to these limitations, we could not fully assess the benefits of different data integration approaches or quantitatively evaluate the contribution of various omics layers for toxicological research questions. Here, we report on a multi-omics study on thyroid toxicity that we conducted in compliance with these best practices. We induced direct and indirect thyroid toxicity through Propylthiouracil (PTU) and Phenytoin, respectively, in a 28-day plus 14-day recovery oral rat toxicity study. We collected clinical and histopathological data and six omics layers, including the long and short transcriptome, proteome, phosphoproteome, and metabolome from plasma, thyroid, and liver. We demonstrate that the multi-omics approach is superior to single-omics in detecting responses at the regulatory pathway level. We also show how combining omics data with clinical and histopathological parameters facilitates the interpretation of the data. Furthermore, we illustrate how multi-omics integration can hint at the involvement of non-coding RNAs in post-transcriptional regulation. Also, we show that multi-omics facilitates grouping, and we assess how much information individual and combinations of omics layers contribute to this approach.

Effect of castor oil on esophageal stricture in rats and expression of ST-2, neopterin proteins in corrosive burn model

Corrosive esophageal burn (CEB) is a disease with high mortality and morbidity rates. The aim of this study was to determine the efficacy of castor oil, in preventing stricture development at the experimental CEB model. In addition to studying standard histopathological damage data, neopterin, IL-33, and ST-2 proteins were also studied for the first time. Fifty Wistar-Albino rats were divided into randomized 5 groups. [Sham group (G1) (n:10), Control group (G2) (n:10), Early Stage Topical Application group (G3)(n:10), Late Stage Topical Application group (G4) (n:10), Oral Application group (G5) (n:10)]. Weight measurement, esophageal length, histopathological damage score (HDS) and total stenosis score (TSS), tissue caspase-3 and VEGF staining, tissue hydroxyproline (HYP), blood TNF-alpha, IL-6, IL-33, Neopterin, and ST-2 levels were measured. In the castor oil application groups, weight gain was observed, the acute phase reaction decreased, submucosal/tunica muscularis fibrosis (TMF) and muscularis mucosal damage (MMD) were reduced, and TSS and HDS decreased. While no significant difference was detected in the ST-2 protein, which was used for the first time in this study model, a significant increase in neopterin protein was observed in the application groups. Results indicate the nutritional contribution of castor oil, as well as its tissue healing and esophageal stricture-preventing efficacy at histopathological and immune-histochemical levels.

Formulation and characterization of cholesterol-based nanoparticles of gabapentin protecting from retinal injury.

This study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats. We prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10-20mg/kg), and diabetic + GAB-SLNs (10-20mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41nm), high negative Zeta potential (-32.18 ± 0.98mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape. GAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF). The preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders.

A Single-Center Analysis of Patient Characteristics and Overall Survival in Patients with Resectable Gallbladder Cancer.

Gallbladder cancer (GBC) is a rare and aggressive hepatobiliary malignancy with poor prognosis. The symptoms of GBC are insidious and non-specific in its early stages, and most patients are diagnosed at advanced or late stages. Surgical resection is the only potentially curative treatment for GBC for select patients. There is a lack of robust data for patients with GBC, leading to heterogenous practices in management strategies and outcomes. In this study, we aimed to identify patient characteristics and cumulative overall survival (OS) in patients with GBC who underwent surgical resection with curative intent. All adult patients (age ≥18 years) with localized or locoregionally advanced GBC who underwent definitive surgery with curative intent at our tertiary institution between 1/2013 and 12/2023 were retrospectively identified. Clinical, laboratory, radiology, histopathology, treatment, and survival data were collected from electronic medical records. Postoperative data included the use of adjuvant chemotherapy or radiotherapy, and patient survival mortality at a cut-off date of 1 February, 2024, calculated from the date of curative surgery. Continuous variables are reported as median and quartile 1 (Q1) and quartile 3 (Q3), while categorical variables are reported as counts and percentages. A total of 94 patients with GBC were included in the study. Median age was 71 (62-77) years and 58 (61.7%) patients were female. Median tumor size was 3.3 (1.9-5.0) cm. Perineural invasion was seen in 48.9% and vascular invasion in 38.3% of patients. A positive surgical margin was present in 50% of the patients, and incidental GBC (IGBC) was seen in 48.9% of patients. Tumor grade was well differentiated in 7.6%, moderately differentiated in 53.3%, and poorly differentiated in 39.1% of the patients. Patients with stage T1a (2.1%) and T1b (11.7%) tumors comprised the minority, and the majority of the tumors were stage T2 (55.3%), followed by T3 (31.9%). A total of 60.6% of patients with GBC underwent adjuvant chemotherapy, and 17% underwent adjuvant radiotherapy after surgical resection. Overall, 62 (66.0%) patients died, and the median OS was 1.88 years. The 1-year OS was 68.7%, 3-year OS was 37.4%, and 5-year OS was 32.2%. A higher absolute median OS was seen in patients who had adjuvant chemotherapy (2.1 years) compared to no chemotherapy (1.9 years); however, this finding was not statistically significant (p = 0.36). The median survival was 2.3 years in IGBC compared to 1.6 years in non-IGBC (p = 0.63). GBC is an aggressive hepatobiliary malignancy that is often diagnosed at advanced stages. Our study showed high rates of local and systemic involvement and high mortality, and the need for prospective and randomized studies on adjuvant therapies to assess their survival benefit. Real-world patient data remain important to identify patients at risk of worse outcomes and to stratify risks prior to surgery.

Value of Quantitative Intraoperative Electrocorticography During Anterior Temporal Lobectomy in Temporal Lobe Epilepsy Patients

Introduction: There is debate on the predictive usefulness of electrocorticography (ECoG) during anterior temporal lobectomy (ATL) in temporal lobe epilepsy (TLE) patients. The purpose of this study was to determine the usefulness of quantitative intraoperative ECoG monitoring for postoperative seizure outcomes after ATL in TLE patients. Methods: The study enrolled thirteen TLE patients who underwent ECoG-assisted ATL. Pre- and post-resection ECoG spike frequency (/min) and spike amplitude (μv/mm) were analyzed with histopathological and preoperative video-electroencephalography (EEG) data. After one year of follow-up, patients were classified as seizure-free (Engel Class I) or with residual seizure outcomes using the Engel Seizure Outcome Classification Scheme. Results: The pre-resection and post-resection ECoG showed significant differences in spike frequency (/min) and amplitude (μv/mm) (P-value < 0.001). Patients with residual seizures (15.4%) showed significantly greater pre- and post-resection ECoG spike frequency and amplitude, as well as significantly higher seizure frequency before surgery, compared to patients with postoperative seizure freedom (84.6%). The pre-resection ECoG spike frequency was significantly greater in TLE patients with histopathology focal cortical dysplasia (FCD) than in those with non-FCD. The post-resection ECoG revealed a sensitivity of 100%, a specificity of 50%, a negative predictive value of 100%, and a positive predictive value of 91.67%. Conclusions: Pre-resection ECoG spike frequency and amplitude can be used as a predictive tool for postoperative seizure outcomes, particularly when video-EEG can't identify the epileptogenic zone (EZ) in TLE patients undergoing ATL.

Diagnostic Accuracy of Bethesda Classification of Thyroid Nodules at a Kenyan Hospital: A Retrospective Study

Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was developed to standardize the reporting of thyroid nodule fine-needle aspiration cytology (FNAC) results. The adoption of TBSRTC is based on the implied risk of malignancy per category, but this has shown wide variation in different regions worldwide. Aim: The aim of this study is to determine the diagnostic accuracy of the Bethesda classification of thyroid nodules in a Kenyan hospital. Methods: A retrospective longitudinal study examined FNAC and histopathology data of thyroid gland nodules at a Kenyan hospital from 2010 to 2019; specimens from 347 patients were found. An analysis was performed to determine the diagnostic accuracy of the Bethesda classification in detecting malignancy among these patients. Results: The malignancy rate was 16.1%. The risk of malignancy as per the Bethesda category was as follows: non-diagnostic— 19.6%, benign—6%, atypia of undetermined significance—20%, follicular neoplasm—16.7%, suspicious for malignancy—80%, and malignant—85.7%. The diagnostic properties of FNAC defining “malignant” and “suspicious for malignancy” categories as malignant were as follows: sensitivity—64.7%, specificity—97.6%, and accuracy—92.7%. Conclusion: The Bethesda classification had high diagnostic accuracy, with the risk of malignancy consistent with the Bethesda findings. Classifying malignancy as “malignant” and “suspicious for malignancy” yielded the most favorable diagnostic properties for FNAC.

Pathogenicity of psychrotolerant strains of Antarctic Pseudogmynoascus fungi reveals potential opportunistic profiles

Recent studies have demonstrated the presence of fungal taxa in the extreme ecosystems of Antarctica that are known to opportunistically infect humans and animals. Among these are members of the genus Pseudogymnoascus, including some that are genetically similar to P. destructans, known to be pathogenic to bats. We evaluated the in vitro and in vivo pathogenic potential of 11 Pseudogymnoascus spp. strains recovered from Antarctica. All strains were able to grow at temperatures up to 28 °C and displayed in vitro pathogenicity through hemolytic activity, growth at different pH levels, production of hydrolytic enzymes, spore diameters, tolerance to oxidative stress, hypoxia, and halotolerance. Among them, Pseudogymnoascus sp. UFMG 8532 exhibited strong in vitro pathogenicity and in preliminary in vivo assay killed 100 % of Tenebrio molitor larvae within one day. The pathogenicity of the same strain was also tested using immunosuppressed BALB/c mouse models. Survival of BALB/c mice was affected, with oscillations between weight gain and loss, and impacts on sensory function, reflexes and autonomic function. Histopathological data from the organs of infected mice showed evidence of inflammatory processes, with numerous neutrophils, a small number of macrophages, fluid accumulation inside the lungs and intense hyperemia. Our results indicate that Antarctic Pseudogymnoascus spp. strains obtained from various substrates/habitats in maritime Antarctica may possess intrinsic virulence factors and pathogenic potential for immunosuppressed animals and humans in the region. Given that the Antarctic environment is an important reservoir for Pseudogymnoascus species, which display growth performance across a range of temperatures, it is possible that increasing temperatures in the maritime Antarctic could activate dormant genes or biochemical pathways, select virulent species and/or strains, and facilitate their spread within and beyond the region. The ability of Pseudogymnoascus species to grow slowly even at 28°C, coupled with their potential in vitro and in vivo virulence factors, suggests that these fungi might be undergoing an opportunistic transition due to the effects of climate change on the Antarctic Peninsula.

Immortelle Essential-Oil-Enriched Hydrogel for Diabetic Wound Repair: Development, Characterization, and In Vivo Efficacy Assessment

Background: Alarming data revealed that 19% to 34% of adults with diabetes mellitus develop chronic wounds, which are characterized by impaired healing and a higher risk of infections. Inspired by the traditional use of immortelle for wound healing and the lack of scientific evidence regarding how it thoroughly influences tissue regeneration, we aimed to formulate a hydrogel loaded with immortelle essential oil and assess its effectiveness on diabetic excision wounds. Methods: The rheological properties of the hydrogel, an in vivo safety test, as well as wound healing capacity, were determined in rats with induced diabetes and excision wounds. Diabetic rats were divided into four groups: untreated, treated with 1% silver sulfadiazine ointment, treated with a gel base, and treated with the immortelle essential oil-based hydrogel. Results: It was revealed that the hydrogel exerts pseudoplastic behavior and has no potential to act as an irritant, thus highlighting its suitability for skin application. Moreover, analysis of macroscopic, biochemical, and histopathological data revealed that the immortelle essential oil-based hydrogel significantly improves wound repair. Superior re-epithelialization, scar maturation, and increased collagen fiber density were achieved after immortelle essential oil-based gel application. Conclusions: These findings suggest that the immortelle essential oil-based hydrogel could be a natural, safe, and effective wound-healing dressing.

Graph neural networks in multi-stained pathological imaging: extended comparative analysis of Radiomic features.

This study investigates the application of Radiomic features within graph neural networks (GNNs) for the classification of multiple-epitope-ligand cartography (MELC) pathology samples. It aims to enhance the diagnosis of often misdiagnosed skin diseases such as eczema, lymphoma, and melanoma. The novel contribution lies in integrating Radiomic features with GNNs and comparing their efficacy against traditional multi-stain profiles. We utilized GNNs to process multiple pathological slides as cell-level graphs, comparing their performance with XGBoost and Random Forest classifiers. The analysis included two feature types: multi-stain profiles and Radiomic features. Dimensionality reduction techniques such as UMAP and t-SNE were applied to optimize the feature space, and graph connectivity was based on spatial and feature closeness. Integrating Radiomic features into spatially connected graphs significantly improved classification accuracy over traditional models. The application of UMAP further enhanced the performance of GNNs, particularly in classifying diseases with similar pathological features. The GNN model outperformed baseline methods, demonstrating its robustness in handling complex histopathological data. Radiomic features processed through GNNs show significant promise for multi-disease classification, improving diagnostic accuracy. This study's findings suggest that integrating advanced imaging analysis with graph-based modeling can lead to better diagnostic tools. Future research should expand these methods to a wider range of diseases to validate their generalizability and effectiveness.

7090 The Largest Study on Asymptomatic Primary Hyperparathyroidism (APHPT) Conducted at the Tertiary Care Riga East Clinical University Hospital (RECUH)— Three Years of Data

Abstract Disclosure: D. Stūrīte: None. I. Rasa: None. Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder and a leading cause of hypercalcemia in the outpatient setting. The study aimed to assess the characteristics, management and outcomes of pts with APHPT. Methods: A retrospective analysis of data from 168 pts with APHPT, evaluated at RECUH from January 2021 to November 2023 was conducted. Information obtained included medical records, laboratory data, imaging results, surgical protocols, histopathology data. Statistical analysis was performed using IBM SPSS 29.0. Results: From the 168 pts (mean age: 63.7±11.8 years), 86.3% (n=145) were females. Predominantly, 67.3% (n=113) exhibited mild hypercalcemia (2.6-3.0mmol/L), while 22.6% (n=38) had moderate hypercalcemia (3.0-3.49mmol/L), and 4.8% (n=8) -severe hypercalcemia (≥3.5mmol/L). 5.3% (n=9) had normocalcaemic PHPT. The mean preoperative maximal calcium level was 2.9±0.3mmol/L, iPTH level - 247.6±224.9pg/mL, minimal phosphorus - 1.3±6.7mmol/L and 25-OH vitamin D level - 28.3±14.7ng/mL. The mean preoperative eGFR was 90.6±28.2 ml/min/1.73m2, creatinine - 72.5±23.9μmol/L. Parathyroid adenoma sizes ranged from 0.3x0.4cm to 5.3x3.7cm. Calcium levels positively correlated with adenoma cross-sectional area (ρ=0.187, p=0.029) and maximal adenoma dimension (ρ=0.215, p=0.011). Ultrasonography convincingly detected parathyroid adenomas in 63.9% (107/168), SPECT/CT - 68.4% (52/76), 99mTc-sestamibi scintigraphy - 65.6% (61/93), 3D-CT - 70.6% (24/34), contrast-enhanced ultrasonography - 84% (21/25) and MRI in - 40% (2/5) cases. 12.5% (n=21) pts had unlocated parathyroid adenoma. 34.5% (n=58) of pts had osteoporosis, 47.6% (n=80) osteopenia, 12.5% (n=21) had a history of osteoporotic fracture, 17.3% (n=29) had gallstones and 22.0% (n=37) - kidney stones. 80.4% (n=135) of pts had thyroid nodules, 48.2% (n=81) - nontoxic goitre, 24.4% (n=31) - autoimmune thyroiditis, 41.7% (n=70) - hypertension, 10.5% (n=18) - type 2 diabetes. 18.5% (n=31) pts were found to have a diagnosis of malignancy. 61.9% (n=104) of pts underwent parathyroidectomy. Histopathology and radiologic imaging revealed single parathyroid adenoma in 95.2% (n=99), double parathyroid adenomas in 1.9% (n=2), parathyroid hyperplasia in 2.9% (n=3) and parathyroid carcinoma in 1.9% (n=2) pts. The mean maximal postoperative calcium level (n=103) was 2.4±0.1mmol/L, iPTH (n=101) - 63.5±27.7pg/mL, 25-OH vitamin D - 41.5±13.3ng/mL, and the mean minimal phosphorus (n=56) - 1.1±0.2mmol/L. Conclusions: APHPT remains frequently encountered and often showcases bone manifestations. It's crucial to consider the diverse clinical manifestations and associated conditions in patients with APHPT. Presentation: 6/2/2024

The prognostic value of the 8th American Joint Committee on cancer anatomic and prognostic stage groups for penile cancer: A multicenter collaboration study

ObjectiveThe aim of this study was to investigate the value of 8th American Joint Committee on Cancer (AJCC) anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement. MethodsThe clinical and histopathologic data from 16 centers between 2000 and 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups. Kaplan–Meier plots were used to estimate the disease-specific survival (DSS) of the patients. The accuracy of the staging systems was investigated using the Harrell's concordance index (C-index). ResultsThe 5-year DSS rates for patients with stages 0is/a, I, IIA, IIB, IIIA, IIIB, and IV (stage 0 to stage IV) disease were 100 %, 98.9 %, 85.5 %, 81.1 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–IIA<0.001, pIIA–IIB=0.486, pIIB–IIIA<0.001, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). According to the modified model 1 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 98.9 %, 87.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–II<0.001, pII–IIIA=0.002, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). Similarly, according to the modified model 2 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 99.0 %, 85.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.757, pI–II<0.001, pII–IIIA=0.008, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). The C-index of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups. These results were confirmed by the bootstrap internal validation. ConclusionThere is still room for improvement about 8th AJCC anatomic and prognostic stage groups. The improved models, which are more concise and convenient, had a similar predictive value.

The sensitivity and specificity of fine needle aspiration cytology in detecting thyroid malignancy according to Bethesda system at a teaching hospital in Saudi Arabia

ABSTRACT Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) aims to standardize the terminology and morphologic criteria associated with thyroid fine-needle aspiration cytology (FNAC) results while also providing corresponding risk assessments for malignancy. contributing to more consistent and standardized reporting of thyroid nodules and aiding clinicians in making informed decisions. Since then, it has been undergoing revisions and updates to further improve its utility and accuracy. Materials and Methods: This is a retrospective study conducted at a tertiary care center. All patients with a history of thyroid gland swelling who had previously undergone FNA were included. The procedure included cytopathologists performing FNAC for all cases of midline neck swelling. Demographic and histopathology data were correlated with the cytological diagnosis. Results: We included 288 cases. Of those, 234 (81.3%) were female and 54 (18.8%) were male. The presentation age range was 18–91 years. The most reported category was benign, which constituted 30.9% of the cases followed by malignancy (27.1%). As for thyroid lesions, papillary carcinoma was the most prevalent (43.6%). The correlation on cyto-histopathology was presented in every diagnostic category, showing high heterogeneity in diagnostic specificity and sensitivity. The overall diagnostic specificity and sensitivity were 56.05% (95% confidence interval [CI]: 47.92–63.95%) and 80.92% (95% CI: 73.13–87.25%), respectively. Positive and negative predictive values were 60.57% and 77.88%, respectively. Conclusion: Our data suggests that the TBSRTC system promotes similar sensitivity and specificity to those reported elsewhere. It standardizes reporting and improves communication between cytopathologists and clinicians.

Multicenter evaluation of CT deep radiomics model in predicting Leibovich score risk groups for non-metastatic clear cell renal cell carcinoma

BackgroundNon-metastatic clear cell renal cell carcinoma (nccRCC) poses a significant risk of postoperative recurrence and metastasis, underscoring the importance of accurate preoperative risk assessment. While the Leibovich score is effective, it relies on postoperative histopathological data. This study aims to evaluate the efficacy of CT radiomics and deep learning models in predicting Leibovich score risk groups in nccRCC, and to explore the interrelationship between CT and pathological features. Patients and MethodsThis research analyzed 600 nccRCC patients from four datasets, dividing them into low (Leibovich scores of 0–2) and intermediate to high risk (Leibovichscores exceeding 3) groups. Radiological models were developed from CT subjective features, and radiomics and deep learning models were constructed from CT images. Additionally, a deep radiomics model and a fusion model integrating radiological, radiomics, and deep learning features were introduced. Model performance was assessed by AUC values, while survival differences across predicted groups were analyzed using survival curves and the DeLong test. Moreover, the research investigated the connection between CT and pathological features derived from whole-slide pathological images in the second validation dataset. ResultsWithin the training dataset, four radiological, three radiomics, and thirteen deep learning features were selected to develop models predicting nccRCC Leibovich score risk groups. The deep radiomics model demonstrated superior predictive accuracy, evidenced by AUC values of 0.881, 0.829, and 0.819 in external validation datasets. Notably, significant differences in overall survival were observed among patients classified by this model (DeLong test p < 0.05 across all datasets). Furthermore, a correlation and complementarity were observed between deep radiomics features and pathological deep learning features. ConclusionsThe CT deep radiomics model precisely predicts nccRCC Leibovich score risk groups preoperatively and highlights the synergistic effect between CT and pathological data.

Sorafenib plus memory-like natural killer cell immunochemotherapy boosts treatment response in liver cancer

BackgroundHeterogeneity of hepatocellular carcinoma (HCC) presents significant challenges for therapeutic strategies and necessitates combinatorial treatment approaches to counteract suppressive behavior of tumor microenvironment and achieve improved outcomes. Here, we employed cytokines to induce memory-like behavior in natural killer (NK) cells, thereby enhancing their cytotoxicity against HCC. Additionally, we evaluated the potential benefits of combining sorafenib with this newly developed memory-like NK cell (pNK) immunochemotherapy in a preclinical model.MethodsHCC tumors were grown in SD rats using subcapsular implantation. Interleukin 12/18 cytokines were supplemented to NK cells to enhance cytotoxicity through memory activation. Tumors were diagnosed using MRI, and animals were randomly assigned to control, pNK immunotherapy, sorafenib chemotherapy, or combination therapy groups. NK cells were delivered locally via the gastrointestinal tract, while sorafenib was administered systemically. Therapeutic responses were monitored with weekly multi-parametric MRI scans over three weeks. Afterward, tumor tissues were harvested for histopathological analysis. Structural and functional changes in tumors were evaluated by analyzing MRI and histopathology data using ANOVA and pairwise T-test analyses.ResultsThe tumors were allowed to grow for six days post-cell implantation before treatment commenced. At baseline, tumor diameter averaged 5.27 mm without significant difference between groups (p = 0.16). Both sorafenib and combination therapy imposed greater burden on tumor dimensions compared to immunotherapy alone in the first week. By the second week of treatment, combination therapy had markedly expanded its therapeutic efficacy, resulting in the most significant tumor regression observed (6.05 ± 1.99 vs. 13.99 ± 8.01 mm). Histological analysis demonstrated significantly improved cell destruction in the tumor microenvironment associated with combination treatment (63.79%). Interestingly, we observed fewer viable tumor regions in the sorafenib group (38.9%) compared to the immunotherapy group (45.6%). Notably, there was a significantly higher presence of NK cells in the tumor microenvironment with combination therapy (34.79%) compared to other groups (ranging from 2.21 to 26.50%). Although the tumor sizes in the monotherapy groups were similar, histological analysis revealed a stronger response in pNK cell immunotherapy group compared to the sorafenib group.ConclusionsExperimental results indicated that combination therapy significantly enhanced treatment response, resulting in substantial tumor growth reduction in alignment with histological analysis.

Sidedness and Molecular Pattern in Defining the Risk of Lymph Node Metastasis in Nonmetastatic Colorectal Cancer: Single-Center Retrospective Study.

Background: Lymphadenectomy plays a central role in the treatment of localized colon cancer. While in left colon cancer the D3 lymphadenectomy/CME is considered the standard of care, lymphatic stations to be removed in right colon cancer are still a matter of discussion. The individuation of LNM risk factors could help in choosing the lymphadenectomy in right-sided tumors. This study aims to analyze the correlation of histopathological and molecular characteristics with lymph node metastasis, both in right- and left-sided colon cancer, and their impact on survival; Methods: We conducted a single-center observational retrospective study. The following data were collected and analyzed for each patient: demographics, histopathological and molecular data, and intraoperative and perioperative data. Statistical analyses were performed, including descriptive statistics, multivariate logistic regression and survival analysis; Results: An association between tumor size (pT, p < 0.001), grading (p = 0.013), budding (p < 0.001), LVI (79,4% p < 0.001) and LNM was observed. A multivariate analysis identified pT4 (OR 5.45, p < 0.001) and LVI+ (OR 10.7, p < 0.001) as significant predictors of LNM. Right-sided patients presented a worse OS when associated with LNM, while no significant difference was observed in N0 patients; Conclusions: histological and molecular analysis can help identify high risk patients, which could benefit from extended lymphadenectomies. These patients could be ideal candidates for the D3 lymphadenectomy/CME.