Histological Outcomes Research Articles

Emerging Technologies in Endoscopy for Gastrointestinal Neoplasms: A Comprehensive Overview.

Gastrointestinal neoplasms are a growing global health concern, requiring prompt identification and treatment. Endoscopic procedures have revolutionized the detection and treatment of gastrointestinal tumors by providing accurate, minimally invasive methods. Early-stage malignancies can be treated with endoscopic excision, leading to improved outcomes and increased survival rates. Precancerous lesions, like adenomatous polyps, can be prevented by removing them, reducing cancer occurrence and death rates. Advanced techniques like chromoendoscopy, narrow-band imaging, and confocal laser endomicroscopy improve the ability to see the mucosa surface and diagnose conditions. Artificial Intelligence (AI) applications in endoscopy can enhance diagnostic accuracy and predict histology outcomes. However, challenges remain in accurately defining lesions and ensuring precise diagnosis and treatment selection. Molecular imaging approaches and therapeutic modalities like photodynamic therapy and endoscopic ultrasonography-guided therapies hold potential but require further study and clinical confirmation. This study examines the future prospects and obstacles in endoscopic procedures for the timely identification and treatment of gastrointestinal cancers. The focus is on developing technology, limits, and prospective effects on clinical practice.

Efficacy Assessment of Five Policosanol Brands and Damage to Vital Organs in Hyperlipidemic Zebrafish by Six-Week Supplementation: Highlighting the Toxicity of Red Yeast Rice and Safety of Cuban Policosanol (Raydel®).

Policosanol is a mixture of long-chain aliphatic alcohols (LCAAs) derived from various plant and insect origins that are marketed by various companies with distinct formulations and brand names. Policosanols offer several beneficial effects to treat dyslipidemia and hypertension; however, a comprehensive functionality comparison of various policosanol brands has yet to be thoroughly explored. In the present study five distinct policosanol brands from different origins and countries, Raydel-policosanol, Australia (PCO1), Solgar-policosanol, USA (PCO2), NutrioneLife-monacosanol, South Korea (PCO3), Mothernest-policosanol, Australia (PCO4), and Peter & John-policosanol, New Zealand (PCO5) were compared via dietary supplementation (1% in diet, final wt/wt) to zebrafish for six weeks to investigate their impact on survivability, blood lipid profile, and functionality of vital organs under the influence of a high-cholesterol diet (HCD, final 4%, wt/wt). The results revealed that policosanol brands (PCO1-PCO5) had a substantial preventive effect against HCD-induced zebrafish body weight elevation and hyperlipidemia by alleviating total cholesterol (TC) and triglycerides (TG) in blood. Other than PCO3, all the brands significantly reduced the HCD's elevated low-density lipoprotein cholesterol (LDL-C). On the contrary, only PCO1 displayed a significant elevation in high-density lipoprotein cholesterol (HDL-C) level against the consumption of HCD. The divergent effect of PCO1-PCO5 against HCD-induced hepatic damage biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), was observed. PCO1, PCO2, and PCO4 efficiently curtailed the AST and ALT levels; however, PCO3 and PCO5 potentially aggravated the HCD's elevated plasma AST and ALT levels. Consistently, the hepatic histology outcome revealed the least effectiveness of PCO3 and PCO5 against HCD-induced liver damage. On the contrary, PCO1 exhibited a substantial hepatoprotective role by curtailing HCD-induced fatty liver changes, cellular senescent, reactive oxygen species (ROS), and interleukin-6 (IL-6) production. Likewise, the histological outcome from the kidney, testis, and ovary revealed the significant curative effect of PCO1 against the HCD-induced adverse effects. PCO2-PCO5 showed diverse and unequal results, with the least effective being PCO3, followed by PCO5 towards HCD-induced kidney, testis, and ovary damage. The multivariate interpretation based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) validated the superiority of PCO1 over other policosanol brands against the clinical manifestation associated with HCD. Conclusively, different brands displayed distinct impacts against HCD-induced adverse effects, signifying the importance of policosanol formulation and the presence of aliphatic alcohols on the functionality of policosanol products.

Histological assessment of a novel de-epithelialization method for connective tissue grafts harvested from the palate. An experimental study in cadavers

ObjectivesThis study aims to compare the histological outcomes of three distinct de-epithelialization methods used in (connective tissue grafts) CTG harvested from the palate.Materials and methodsAn experimental study using nine cadaver head specimens was carried out to compare 3 different de-epithelialization techniques for CTG. Eighteen samples were randomly allocated to three study groups: bone scraper, diamond bur and extraoral removal with a scalpel. The main outcome variable was the graft surface percentage without epithelium remains. Additionally, the time employed, and the graft thickness were also measured.ResultsSixteen CTGs were analyzed. The extraoral scalpel group presented a total surface area with no epithelium of 58.84% (22.68) and a mean de-epithelialization time of 3.7 min; the intraoral diamond bur group had 88.24% (41.3) of the surface with no epithelium and took 1.455 min, and the intraoral bone scraper showed 97.98% (5.99) of surface without epithelium and a mean time of 0.815 min (P < 0.05). Histological analysis showed significant differences between the bone scraper and the extraoral group (P = 0.009).ConclusionThe de-epithelialization technique with a bone scraper seems to be the most effective and fastest de-epithelialization technique for CTG. These findings need to be confirmed in future clinical studies with larger samples.Clinical relevanceThe use of bone scrapers, could be a simple, effective and fast technique to de-epithelialize connective tissue grafts harvested from the palatal area for both novice and experienced surgeons.

Comparison of budesonide vehicles in inducing histologic remission in pediatric eosinophilic esophagitis.

Oral viscous budesonide (OVB) is a common medication used to treat eosinophilic esophagitis (EoE). It is typically mixed with Splenda to produce a slurry, but other delivery vehicles have been used in clinical practice. We aimed to evaluate outcomes of pediatric EoE patients treated with OVB using different drug delivery vehicles. We performed a retrospective chart review of pediatric EoE patients treated with OVB. The primary aim was to evaluate rates of histologic remission (defined by <15 eos/HPF in both mid and distal esophagus) after 6-12 weeks of OVB treatment for each delivery vehicle. Secondary aims were to evaluate histologic response and endoscopic response and remission of different delivery vehicles, and to compare the efficacy of different treatment regimens. A total of 111 patients were included in the study. Median treatment duration was 3.4 months. Overall rate of histologic remission with OVB was 52.6%. There was no difference in rates of histologic remission (p = 0.313) or response (p = 0.195 and p = 0.681 in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission and response among the different vehicle types (p = 0.853 and p = 0.727) or treatment regimens (p = 0.244 and p = 0.157). Patients who achieve histologic remission were more likely to be non-Hispanic Caucasian. Our findings suggest there is no difference in histologic and endoscopic outcomes with various delivery vehicles or combination therapy with OVB in the treatment of EoE. More palatable and cost-effective vehicles can be used to treat EoE.

Porocarcinoma: Clinical and Histological Features, Immunohistochemistry and Outcomes: A Systematic Review.

Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and distant metastasis is high. Differential diagnosis with squamous cell carcinoma is difficult, although NUT expression and YAP1 fusion products can be very useful for diagnosis. Currently, wide local excision is the main surgical treatment, although Mohs micrographic surgery is promising. To date, there is no consensus regarding the role of sentinel lymph node biopsy and consequential lymph node dissection. No guidelines exist for radiotherapy, which is mostly performed based on tumor characteristics and excision margins. Only a few studies report systemic treatment for advanced PC, although therapy with pembrolizumab and EGFR inhibitors show promise. In this review, we discuss epidemiology, clinical features, histopathological features, immunohistochemistry and fusion products, surgical management and survival outcomes according to stage, surgical management, radiotherapy and systemic therapy.

#1039 Characteristics and outcome of IgA nephropathy in Switzerland – a single center perspective

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide leading to end-stage kidney disease (ESKD) in roughly 40% of affected patients by ten years. Geographic differences in clinical course and response to treatment may partly result from different disease entities. The purpose of this retrospective cohort analysis was to study all cases of IgAN from a single tertiary center with respect to clinical and histological characteristics, treatment practices and outcome. Method This retrospective cohort analysis identified 158 cases of adult biopsy-proven IgAN by chart review diagnosed between 1980 and 2017. Detailed phenotypisation including clinical, paraclinical, histological, treatment and outcome parameters was performed. Remission status was defined as described previously (Reich 2007). Statistical analysis was performed using Excel and SPSS software and included standard descriptive methods and included standard descriptive methods and student's t-test on a significance level of 0.05. Results Subjects were majorly male and of Caucasian descent. Mean estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration formula at diagnosis was 55.3 ml/min/1.73 m2, mean proteinuria was 3.2 g/d. 70.3% of patients were hypertensive at presentation. Clinical presentation varied according to age. Thus, younger patients (18-39 years) presented more frequently with macrohematuria, asymptomatic urine abnormalities and by trend acute kidney injury whereas nephrotic syndrome and extrarenal symptoms were recorded in similar proportions of patients (Fig. 1). 28.5% of initial biopsies showed moderate to severe tubular atrophy and interstitial fibrosis (IFTA), 38% included crescents, 1.9% &amp;gt; 50% crescents. 86.1% of the patients were treated by renin-angiotensin-aldosterone-system inhibitors, 46.8% received immunosuppressive therapy including steroids in 46.2% and other immunosuppressive medications in 19.6% the most common being azathioprine (Fig. 2). There were 33.5% complete and 13.3% partial remissions. Progression to ESKD was noted in 42.1%. 51.4% of patients treated with immunosuppressive therapy experienced remission. Recurrence rate after transplantation was 18.4%. Patients treated by immunosuppressants had higher levels of baseline proteinuria (3.2 ± 2.3 vs. 1.6 ± 1.6 g/d, p &amp;lt; 0.00001), lower baseline eGFR (50 ± 31 vs. 61 ± 30 ml/min/1.73 m2, p = 0.04), higher number of crescents (9.4 ± 15.0 vs 2.3 ± 8.5%, p = 0.001), higher IFTA scores (1.7 ± 0.8 vs. 1.3 ± 0.6, p = 0.007) and higher fluorescence intensity scores for C3 (2.0 ± 0.9 vs. 1.6 ± 0.9, p = 0.02) on initial biopsy as compared to patients treated conservatively. Patients progressing to ESKD presented with higher blood pressure (146 ± 26 vs. 135 ± 18 mmHg systolic, p = 0.005; 89 ± 14 vs. 82 ± 14 mmHg diastolic, p = 0.006), lower eGFR (41 ± 29 vs. 64 ± 28 ml/min/1.73 m2, p = 0.00001), higher levels of proteinuria (3.4 ± 2.0 vs. 1.8 ± 1.9 g/d, p = 0.0001), higher number of crescents (9 ± 17 vs. 4 ± 9%, p = 0.03) and higher IFTA scores (1.8 ± 0.8 vs. 1.3 ± 0.6, p = 0.00001) as compared to patients without ESKD at last follow up. Baseline blood pressure (134 ± 18 vs. 147 ± 26 mmHg systolic, p = 0.004; 82 ± 14 vs. 89 ± 15 mmHg diastolic, p = 0.01), eGFR (60 ± 29 vs. 41 ± 27 mmHg, p = 0.0007), proteinuria (2.3 ± 1.9 vs. 3.2 ± 2.3 g/d, p = 0.03) and severity of IFTA (1.4 ± 0.6 vs. 1.8 ± 0.9, p = 0.003) differed significantly between patients who experienced any remission vs. those who did not achieve remission respectively. Conclusion This analysis gives insight into the characteristics and treatment practices of a Swiss single center cohort of IgAN patients from 1980-2017.

#2724 Renal amyloidosis cohort registry in our health area

Abstract Background and Aims Renal amyloidosis is the pathological phenomenon of amyloid deposition in the kidney with marked differences in renal function impairment, proteinuria, need for renal replacement therapy (RRT) and exitus, depending on the protein involved. Light chain amyloidosis (AL) and serum protein A (AA) amyloidosis are the most common. Typical symptoms are severe proteinuria, nephrotic syndrome, and end-stage chronic kidney disease (ESRD). Method Retrospective study of a cohort of patients with renal amyloidosis. Data extracted from the biopsy registry of the HUVM Nephrology Service (2013-2022). We collected demographic, clinical, analytical, histological and clinical outcome variables (RTT, Exitus). Results are analyzed using Mayo Clinic staging criteria. Results 19 patients with a mean age of 63.4a; 57.9% male. Mean laboratory values at diagnosis: creatinine (Cr) 1.56 mg/dl and proteinuria 3.9 g/24 h. Abdominal fat biopsy in 13 cases; 3 (23%) tested positive. Comparative analysis of AL vs non-AL forms, Cr values (1.14 vs 2.27 mg/dl respectively) (p=0.57) differed. Proteinuria according to the histological location of the amyloid: 4.6 g/24 h in glomerular involvement vs. 0.3 g/24 h in those who did not present it (p&amp;lt;0.05). 31.6% required RTT with a mean onset time of 250.6 d from biopsy. Exitus of 21.1%: average time of 426.5 d. (See analysis in attached table). Conclusion We did not observe significant deterioration of renal function, which is greater in non-AL forms of amyloidosis. Fat biopsy was less cost-effective than reported in the literature. Significantly lower levels of proteinuria were found in the amyloidosis group without glomerular involvement. In our series, the prognostic capacity associated with the MAYO staging was confirmed.

#57 Tubular biomarkers in proteinuric kidney diseases

Abstract Background and Aims Proteinuria is not only a biomarker of chronic kidney disease (CKD) and a risk predictor of adverse outcomes but also a driver of kidney disease progression. The excessive filtration of plasma proteins through the glomerular filtration barrier exerts a toxic effect on tubular cells which ultimately leads to fibrosis and end-stage kidney disease (ESKD. The aim of this study was to assess the levels of various tubular biomarkers in both serum and urine in patients with biopsied glomerular and proteinuric kidney diseases, and correlate them with renal histology and kidney outcomes. Method A retrospective study and observational study was conducted at a single center from January 2016 to December 2021. Serum and urine samples were collected on the same day of renal biopsy and were correlated with histological data from a cohort of 156 patients with proteinuric kidney diseases. Kidney outcomes were registered during a median follow-up period of 26 months and defined as a decrease in eGFR ≥ 40% from baseline or the development of end-stage kidney disease. The following urinary markers, adjusted to urine creatinine, were analyzed: β2-mcg (beta 2 microglobulin), α1-mcg (alpha 1 microglobulin), NGAL (Neutrophil Gelatinase-Associated Lipocalin), uKIM-1 (Kidney Injury Molecule-1), MCP-1 (Monocyte Chemoattractant Protein-1), uDKK-3 (urinary Dickkopf-3), and uUMOD (uromodulin). Serum markers sKIM-1 and uUMOD were also collected. Results Regarding the etiology of proteinuric kidney disease, the majority corresponded to glomerular disease (68.6%) followed by diabetic kidney disease (12.8%). Higher levels of proteinuria were associated with increased values of β2-mcg and α1-mcg levels and low levels of uUMOD and sUMOD. A significant correlation between the extent of interstitial fibrosis and specific biomarkers was observed: uDKK3 (rho = 0.804, p &amp;lt; 0.001), sKIM-1 (rho = 0.472, p &amp;lt; 0.001), sUMOD (rho = −0.370, p &amp;lt; 0.001), uUMOD (rho = −0.317, p &amp;lt; 0.001), MCP-1 (rho = 0.374, p &amp;lt; 0.001), uKIM-1 (rho = 0.368, p &amp;lt; 0.001), and β2-mcg (rho = 0.392, p &amp;lt; 0.001). Multivariate regression analysis identified uDKK3 as an independent predictor of interstitial fibrosis (Beta 0.728, p &amp;lt; 0.001) adjusted for age, serum creatinine and proteinuria. Elevated levels of MCP-1 and uKIM-1 were associated with a higher risk of significant cortical interstitial inflammation &amp;gt;10% in the logistic regression analysis adjusted for eGFR, proteinuria, and microhematuria: MCP-1 OR = 5.14, 95% CI (2.27−11.62), p &amp;lt; 0.001 and uKIM-1 OR = 1.64, 95% CI (1.05−2.58), p = 0.031. Patients with higher tertiles of β2mcg, MCP1, uDKK3, and KIM1s, and lower tertiles of uUMOD and sUMOD experienced a significantly reduced renal event-free survival in the analysis of Kaplan-Meier model (Fig.). Moreover, of all the evaluated markers, uDKK3 was identified as the best predictor of renal events [HR = 1.03, 95% CI (1.01−1.06), p = 0.008], independently of age, baseline eGFR, proteinuria, and the extent of interstitial fibrosis at the time of renal biopsy. Conclusion Tubular biomarkers may offer prognostic value in proteinuric kidney diseases, particularly uDKK3, exhibiting a notable correlation with interstitial fibrosis and serving as a potential predictor of CKD progression.

Malignant risk of pediatric Bethesda category III thyroid nodules subcategorized by nuclear atypia and other: A single institution experience.

The 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) divides AUS diagnoses into two major subcategories: atypia of undetermined significance (AUS) nuclear atypia (AUS-N) and other (AUS-O). This study aims to compare the histological outcome and malignant rate of pediatric AUS thyroid nodules classified into AUS-N and AUS-O subcategories. A search of our institutional electronic pathology database for the period from January 2012 to July 2023 was conducted to identify pediatric (<21 years old) thyroid nodules that were interpreted as AUS and subsequently had surgery. Cases were further divided into AUS-N and AUS-O subcategories. Results of follow-up surgical resections were collected. The malignant rate was calculated and compared between AUS-N and AUS-O groups. The study identified 62 thyroid nodules from 58 pediatric patients. Among these nodules, 29 and 33 were subcategorized as AUS-N and AUS-O, respectively. Both groups exhibited a female predominance and displayed a similar nodule size distribution. Histological analysis revealed 15 carcinomas in AUS-N nodules, including 11 cases of classic papillary thyroid carcinoma (PTC) and four cases of follicular type of PTC. In contrast, in the AUS-O group, a total of five carcinomas were documented, including two PTCs and three oncocytic thyroid carcinomas. Notably, the malignant rate of AUS-N nodules (52%) is significantly higher than that of AUS-O nodules (15%) (p=.002). In pediatric AUS thyroid nodules, the malignant risk in AUS-N is significantly higher than that in AUS-O. These findings may guide more appropriate clinical triage and/or improve management of pediatric patients with AUS thyroid nodules.

Gastroscopy Yield in the Young: Comprehensive Assessment of Endoscopic and Histologic Findings—A Comparative Study

Background. The escalating utilization of gastroscopy in young individuals necessitates an in-depth examination of its diagnostic yield and outcomes in this population. This study aims to investigate and compare various aspects of gastroscopy between young and older adults, shedding light on age-related differences in indications, endoscopic findings, histologic outcomes, and clinically significant findings (CSFs). Methods. A retrospective, large cohort study spanning five years, focused on consecutive patients undergoing gastroscopy. We analyzed age subgroups, specifically categorizing patients into those aged 30 and below, 30–39, 40–49, and a control group aged 50 and above. The investigation aimed to compare various aspects of gastroscopy outcomes among these distinct age categories. Indication-based analyses were conducted to assess the yield and outcomes in these subgroups, focusing on CSFs and the number needed to investigate (NNTI). Results. A total of 1313 young patients aged 16–49 and 3396 controls aged 50 and above were included. Among the young patients, unspecified epigastric pain and dyspepsia emerged as a prevalent indication, accounting for 41.5% of cases. Endoscopic findings revealed a significantly higher diagnosis rate of gastritis than controls (48.2% vs. 35.7%; p&lt;0.001). Histologic analysis demonstrated a substantially elevated rate of H. pylori-associated gastritis in the young (41.1% vs. 29%; p&lt;0.001). Notably, although significantly lower than older controls, precancerous lesions were detected in 7.5% of young patients. CSFs’ diagnosis rate displayed a clear age-dependent increase. Particularly, gastroscopy for upper gastrointestinal bleeding and iron deficiency anemia were associated with higher CSF rates across all young-age subgroups. In multivariate analysis, age and indications of upper gastrointestinal bleeding and iron deficiency anemia were predictors of CSFs’ detection in young patients. Conclusion. This study comprehensively delineates various facets of gastroscopy in the young population, elucidating age and indication-specific patterns in endoscopic and histologic findings, and clinically significant outcomes.

Myoepithelial Tumors of Bone With EWSR1::PBX3 Fusion: A Spectrum From Benign to Malignant

The EWSR1::PBX3 fusion gene, commonly associated with cutaneous syncytial myoepitheliomas, is also found in myoepithelial tumors (METs) of bone and soft tissue. These tumors typically demonstrate benign histology and favorable outcomes. This study examines 6 previously unreported intraosseous METs harboring the EWSR1::PBX3 fusion, focusing on their histopathologic characteristics, immunophenotype, clinical and radiographic profiles, and patient outcomes. The cohort comprised 5 men and 1 woman, aged 25 to 65 years (median age: 31 years), with tumors located in the proximal tibia (3 cases), distal radius (2 cases), and ilium (1 case) and sizes between 3.2 and 12.2 cm (median size: 3.9 cm). Imaging showed osteolytic lesions with varying degrees of cortical involvement and soft tissue extension in 3 cases. Histologically, 4 tumors showed mainly uniform oval-to-spindled cells in syncytial or fascicular arrangements within a collagenous matrix, displaying either bland nuclear features or mild atypia, and low to slightly elevated mitotic activity (≤1 per 10 high-power fields in 3 cases and 6 per 10 high-power fields in 1), classifying them as benign or atypical METs. In contrast, 2 tumors exhibited pronounced nuclear atypia with ovoid, spindled, epithelioid and round cells, hyperchromatic nuclei, inconspicuous nucleoli, increased N/C ratios, high mitotic rates (17 and 19 per 10 high-power fields), and extensive necrosis. Both tumors behaved aggressively—one patient underwent amputation after neoadjuvant chemotherapy and radiation, and the other died within 7 months with the disease still present. Immunohistochemically, the tumors consistently expressed epithelial membrane antigen and S100 but lacked keratin (AE1/AE3) expression. Our study demonstrated that bone METs with EWSR1::PBX3 fusions encompass a histologic continuum from benign to malignant, with benign/atypical METs mirroring their cutaneous analogs in morphology, and malignant variants distinguished by heterogeneous cytologic and architectural features, pronounced nuclear atypia, and high mitotic rates.

Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation.

The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.

Comparison of short-term outcomes of laparoscopic surgery, robot-assisted laparoscopic surgery, and open surgery for lateral lymph-node dissection for rectal cancer: a network meta-analysis.

This study attempted to compare short-term outcomes of laparoscopic surgery (LS), robot-assisted laparoscopic surgery (RS), and open surgery (OS) for lateral lymph-node dissection (LLND) in treatment of rectal cancer through network meta-analysis.Embase, Web of Science, PubMed, and The Cochrane Library databases were searched to collect cohort studies on outcomes of LS, RS, and OS for LLND for rectal cancer. Newcastle-Ottawa Scale (NOS) was utilized to evaluate the quality of cohort studies. Primary outcomes should at least include one of the following clinical outcome measures: operative time, blood loss, total lymph-node harvest, positive resection margin rate, postoperative complications, and postoperative hospital stay. A network meta-analysis was conducted using STATA software.Fourteen cohort studies including 8612 patients were eligible for inclusion. The network meta-analysis results showed that, in terms of intraoperative outcomes, the RS group had the longest operative time, while the OS group had the shortest; the LS and RS groups had significantly less blood loss than the OS group. In terms of histological outcomes, there were no significant differences in the total number of lymph nodes harvested and the positive margin rate among the LS, RS, and OS groups (P > 0.05). Regarding postoperative outcomes, the OS group had the highest probability of postoperative complications and the longest hospital stay, followed by the LS group, with the RS group being the lowest.RS was the best method in blood loss, postoperative complication rate, and postoperative hospital stay, followed by LS. OS had the shortest operative time and the highest blood loss.

Non-Hispanic Black Persons With Nonalcoholic Fatty Liver Disease Have Lower Rates of Advanced Fibrosis, Cirrhosis, and Liver-Related Events Even After Controlling for Clinical Risk Factors and PNPLA3 Genotype.

Nonalcoholic fatty liver disease (NAFLD) is less frequent in non-Hispanic persons (NHB), but there are knowledge gaps in our understanding of disease severity and outcomes of NAFLD in NHB. We compared liver histology and clinical outcomes of NAFLD in non-Hispanic Black persons (NHB) and non-Hispanic White persons (NHW). We compared liver histology and outcomes of 109 NHB and 1,910 NHW adults with biopsy-proven NAFLD participating in the Nonalcoholic Steatohepatitis Clinical Research Network observational studies. The relationship between self-reported NHB race/ethnicity and advanced fibrosis was assessed through multivariable logistic regression after controlling for clinical covariates and PNPLA3 genotype. NHB and NHW with NAFLD had similar NAFLD activity scores (NAS, 4.4 vs 4.3, P = 0.87) and proportions with definite metabolic dysfunction-associated steatohepatitis (59% vs 58%, P = 1.0), but NHB had significantly lower rates of advanced fibrosis (22% vs 34%, P = 0.01) or cirrhosis (4.6% vs 12.1%, P = 0.010). Compared with NHW, NHB had significantly lower frequency of advanced fibrosis (Odds Ratio: 0.48, 95% Confidence Interval: 27-0.86, P = 0.01). In a comparison between 24 NHB and 655 NHW with advanced fibrosis, the NAS (5.6 vs 4.9, P = 0.01) and lobular inflammation grade (2.2 vs 1.7, P < 0.002) were significantly higher among NHB with advanced fibrosis. One NHB and 23 NHW died during follow-up (0.30 vs 0.28 per 100 person-year follow-up). Seven and zero liver-related deaths occurred in NHW and NHB with NAFLD, respectively. The risk of advanced fibrosis in NHB with NAFLD is significantly lower, after controlling for clinical risk factors and PNPLA3 genotype. Although their risk of advanced fibrosis was low, NHB with NAFLD and advanced fibrosis had higher NAS and lobular inflammation, indicating a difference in their relationship between necroinflammation and fibrosis.

Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study

ObjectivesDeveloping a deep learning radiomics model from longitudinal breast ultrasound and sonographer’s axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer.MethodsBreast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model’s performance against sonographer’s diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection.ResultsIn the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer’s diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer’s diagnostic ability, increasing accuracy from 71.9% to 79.2%.ConclusionThe deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery.Clinical relevance statementOur AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer’s axillary diagnosis.Key PointsAxillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound.Our AI model outperformed sonographer’s visual diagnosis on axillary ultrasound.Our deep learning radiomics model can improve sonographers’ diagnosis and might assist in surgical decision-making.

Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers.

Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes. A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (β2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months. Multivariate regression analysis identified sUMOD (β-0.357, P<.001) and uDKK3 (β 0.483, P<.001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52-69.20] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04-4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria. Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain.

B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro and cerebral ischemia in vivo. However, its other biological functions remain unclear. This study aims to investigate whether B355252 suppresses neuroinflammatory responses and cell death in the brain. C57BL/6j mice were intraperitoneally injected with a single dosage of lipopolysaccharide (LPS, 1 mg/kg) to induce inflammation. B355252 (1 mg/kg) intervention was started two days prior to the LPS injection. The animal behavioral changes were assessed pre- and post-LPS injections. The animal brains were harvested at 4 and 24 h post-LPS injection, and histological, biochemical, and cytokine array outcomes were examined. Results showed that B355252 improved LPS-induced behavioral deterioration, mitigated brain tissue damage, and suppressed the activation of microglial and astrocytes. Furthermore, B355252 reduced the protein levels of key pyroptotic markers TLR4, NLRP3, and caspase-1 and inhibited the LPS-induced increases in IL-1β, IL-18, and cytokines. In conclusion, B355252 demonstrates a potent anti-neuroinflammatory effect in vivo, suggesting that its potential therapeutic value warrants further investigation.

Histological Outcomes of Pharmacological Interventions in Eosinophilic Esophagitis for Adults and Children: A Network Meta-analysis of Randomized Controlled Trials.

Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children. We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes. Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5mg twice daily, fluticasone 3mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3mg daily, cendakimab 180mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5mg daily, OVB low dose, reslizumab 3mg/kg, reslizumab 1mg/kg, and reslizumab 2mg/kg. Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.

Abstract PS16-08: Histologic Pattern and Outcomes in High-Grade Metaplastic Breast Cancer Compared to Triple-Negative Ductal Breast Cancer Counterparts: A Single Institution Retrospective Study

Abstract Background Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer that presents with high tumor stage and a poor prognosis. MpBC tumors tend to have worse outcomes compared to other non-metaplastic triple-negative breast cancers (TNBC). Although MpBC has been described as chemotherapy resistant, chemotherapy remains a mainstay of treatment. MpBC tumors can be further characterized by their specific histologic pattern. The existing literature on outcomes of MpBC by histologic pattern is limited, with varying results regarding response rate and overall survival (OS). Identifying a pattern of MpBC that has better response to treatment could help tailor treatment recommendations. Methods A retrospective chart review was performed and identified 106 patients with early-stage, high-grade MpBC who were diagnosed at Levine Cancer Institute between January 1, 2010 and September 1, 2021. A matched control cohort (n=106) of patients diagnosed with non-metaplastic TNBC was selected based on propensity score matching on diagnosis date, age at diagnosis, race, pathologic staging, and tumor grade. Patient demographics, tumor characteristics, therapeutic interventions, residual cancer burden (RCB), and outcomes were collected. The associations between the histologic patterns of MpBC and disease characteristics were evaluated using chi-squared tests for categorical variables and Wilcoxon tests for continuous variables. We also examined the differences in RCB scores between the MpBC cohort and the non-metaplastic TNBC cohort who received neoadjuvant chemotherapy. Additionally, Kaplan-Meier and Cox proportional hazard analysis was performed to assess differences in recurrence free survival (RFS) and OS between the spindle cell/sarcomatous pattern versus all other patterns. Results For the entire group (n=212), median age at diagnosis was 58 years (range, 24-92); all patients were female; 66% White, 29% Black, and 5% unknown race. Most tumors were triple-negative (91%); 19%, 56% and 14% with Clinical Stage I, II, and III disease, respectively. A total of 63% of patients underwent radiation treatment and 76% received chemotherapy (43% neoadjuvant and 57% adjuvant). Recurrence after treatment occurred in 16% of all patients. In the MpBC cohort (n=106), the histologic patterns included spindle cell/sarcomatous (34%), squamous (17%), heterologous mesenchymal (31%), mixed (17%), and other (1%). Of those with MpBC who received neoadjuvant chemotherapy (n=32), RCB among the different histologic patterns was assessed. When comparing spindle cell/sarcomatous versus the other histologic patterns combined, there was no significant difference in RCB (p = 0.81), although more RCB III scores were recorded in the spindle cell/sarcomatous pattern compared to the other MpBC patterns (40% versus 30%). When assessing RFS and OS by histologic pattern in the entire MpBC cohort, spindle cell/sarcomatous tumors had inferior RFS (p = 0.0194) and OS (p = 0.0039) compared to the other MpBC patterns combined. When comparing RCB values between MpBC and non-metaplastic TNBC, there were numerically more RCB-III classes in the MpBC cohort as compared to the non-metaplastic TNBC. Conclusion MpBC is an aggressive and difficult breast malignancy to treat. Based on our single institution review, no correlation between RCB and the histologic pattern of MpBC was found, however, RFS and OS were worse among the spindle cell/sarcomatous pattern. Furthermore, the MpBC cohort had numerically higher RCB-III scores than the TNBC control cohort, which is in line with historical data. Citation Format: Ashley Matusz-Fisher, Annabel Chen, Erin Donahue, Courtney Schepel, Michelle Wallander, Chad Livasy, Richard White, Antoinette Tan, Lejla Hadzikadic-Gusic. Histologic Pattern and Outcomes in High-Grade Metaplastic Breast Cancer Compared to Triple-Negative Ductal Breast Cancer Counterparts: A Single Institution Retrospective Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-08.

Recurrent postmenopausal bleeding: Pathological findings andpredictive factors. A multicenter, prospective, observational study.

Recurrent postmenopausal bleeding (PMB) occurs in 6%-25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB. A multicenter prospective cohort study was conducted over a 5-year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode vs recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB. A total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow-up of 61 months (IQR (Interquartile range)44-73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p-value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p-value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75-23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64-6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07-3.04). Recurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy.