Histological Index Research Articles

Water extract of yarrow (Achillea millefolium L.) leaf improves production parameters, tissue antioxidant status and intestinal microbiota activity in turkeys

This study aimed to analyze the effect of water extract of yarrow (Achillea millefolium L.) leaf (WEYL) on tissue oxidative properties, histological indices, gut microbiota composition and activity, and production parameters in turkeys. A total of 360 (1-day-old) female poults were randomly assigned to one of three treatments (8 replications × 15 poults each). The turkeys were fed in a four-phase system for 15 weeks: group C (control)—diet that did not contain WEYL; group E1—diet supplemented with 0.05, 0.1, 0.1, and 0.2 g/kg WEYL; and group E2—diet supplemented with 0.1, 0.2, 0.2, and 0.3 g/kg WEYL. The results of the analyses of body weight, feed intake, and feed conversion indicated that WEYL did not have any effect on these parameters (P > 0.05). However, WEYL increased the proportion of skin with subcutaneous fat (P = 0.006), and when supplemented at higher ratios, it reduced the proportion of liver (P = 0.010) and improved slaughter performance (P = 0.044). Furthermore, consumption of WEYL-supplemented diet led to an improvement in the antioxidative status and glutathione peroxidase activity in the blood and breast muscles, and also increased the superoxide dismutase activity in the blood and liver (P < 0.05). Supplementation with WEYL at a lower dose (E1) resulted in reduced malondialdehyde concentration in the blood, while supplementation at a higher dose (E2) caused a reduction in ascorbic acid concentration in the liver (P < 0.05). Turkeys that were fed with WEYL-containing diet had a higher amount of cholinesterase in the blood (P = 0.045), and those fed with the diet containing a higher dose of WEYL (E2) had a higher level of albumins and total protein (P < 0.05). Turkeys from E2 group had the longest villi and shallowest crypts, but the percentage of proliferating nuclei was found to be the highest in the group that received a diet with a lower dose of WEYL (E1) (P < 0.05). Turkeys from E2 group showed a decreased relative abundance of Lactobacillus spp. in the cecal content as well as reduced β-glucosidase activity, while those from the E1 group showed reduced β-galactosidase activity (P < 0.05). In summary, dietary supplementation with WEYL can help improve tissue antioxidative status and modify the enzymatic activity of the cecal microflora in turkeys, with no negative influence on the production outcomes of these birds.

Histological Indices and Risk of Recurrence in Crohn's Disease: A Retrospective Study of a Cohort of Patients in Endoscopic Remission.

Although histological healing is raising interest in ulcerative colitis to predict recurrence, its meaning in Crohn's disease (CD) remains unknown. We aimed to study the performances of different histological indices to predict recurrence of CD patients with mucosal healing. Crohn's disease patients with mucosal healing diagnosed between 2010 and 2018 were included if there was available clinical and endoscopical data. Nancy Histological index (NHI), Geboes score (GS), Robarts Histopathology index (RHI), Global Histological Disease Activity Score (GHAS), and Inflammatory Bowel Disease-Distribution Chronicity Activity score (IBD-DCA) were independently assessed by 3 pathologists. Eighty-eight patients were included, of which 28 relapsed (32%) within 30.5 months. All 4 histological indices were associated with recurrence, with significant relapse risk (NHI, odds ratio [OR], 1.67; GHAS, OR, 2.33; RHI, OR, 1.19; GS, OR, 2.09; and IBD-DCA, OR, 2.14). Microscopic activity was significantly associated with relapse only with the IBD-DCA score. Predicting performances of all these scores were poor. Calibration curves indicate that the GHAS and IBD-DCA are the closest to the ideal predicted probability curve and thus could better predict recurrence than the other scores. Interobserver agreement varied from poor for GHAS (k = .39) to good for RHI (k = .68). Histological scores are valuable indicators to predict recurrence. Histological assessment of activity seems insufficient to predict CD course with most of the score evaluated, highlighting the need for new indices or adaptation of actual scores to CD specificities.

Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score.

The NASH Clinical Research Network histologic scoring system, the gold-standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS). Four liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80-0.85) and interrater (0.60-0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68-0.79), including those extending scores from 0-2 to 0-4. Steatosis measures (interrater ICCs, 0.72-0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory-Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70-0.87. After extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required.

Ethyl acetate fraction of Fagara zanthoxyloides root-bark possess antidiabetic property against alloxan-induced diabetes and its complications in Wistar rat model

Ethnopharmacological relevanceFagara zanthoxyloides Lam., an African traditional medicinal plant, is used for treatment of malaria and diabetes. AimTo investigate the antidiabetic property of ethyl acetate fraction of F. zanthoxyloides root-bark (EAFFZRB) on alloxan-induced diabetic rats. Materials and methodsExtraction, isolation, preliminary phytochemical analysis, and acute toxicity study of ethanol extract and fractions of F. zanthoxyloides root-bark were achieved using standard methods. Phyto-constituents in EAFFZRB were identified using HPLC technique. Forty-eight male Wistar rats (140–185 g) were randomized into 6 groups (n = 8). Groups 1 and 2 served as normal and negative controls, respectively. Diabetes was induced in test groups (2–6) using 150 mg/kg body weight (b.w) Alloxan monohydrate. Rats in groups 4–6 received of 200, 400 and 600 mg/kg b.w. EAFFZRB orally, respectively, for 21 days. Group 3 rats received 5 mg/kg b.w Glibenclamide. The effect of EAFFZRB on alterations in hematological, biochemical, and histological indices of study rats were assessed. ResultsExtraction of 3500 g ethanol extract yielded 15.71 g EAFFZRB. HPLC fingerprint of EAFFZRB indicated presence of luteolin, rutin, quercetin, apigenin, cinnamic acid and catechin. Diabetes triggered significant (p < 0.05) alterations in b.w., hematological, biochemical and histological indices of test rats relative to normal control. Treatment with EAFFZRB (LD50 = 3807.9 mg/kg b.w.) resulted in remarkable improvements in altered b.w. changes, hematological, biochemical and histological parameters of diabetic rats. ConclusionThe study demonstrated the antidiabetic potential of EAFFZRB, providing scientific basis for traditional use of the plant in treatment of diabetes and its complications.

Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.

BackgroundTriple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population.MethodsWe recruited 89 patients with TNBC at Guangdong Provincial People’s Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies.ResultsCases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035).ConclusionsIn TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.

Reproductive potential and histological profiling of the wild female anadromous shad (Tenualosa ilisha) in lower Meghna Estuary, Bangladesh

Hilsha shad (Tenualosa ilisha, Hamilton 1822) is the most commercially important and national fish of Bangladesh, belongs to the family of Clupeidae of the Clupeiformes. The study was conducted to identify the seasonal gonadal cycles through histological study and the peak breeding season combining histological and Gonado Somatic Index (GSI). One hundred and twenty fish samples with an average weight of 756.75±6.25 g was collected from the Tentulia river for the study throughout the year. Monthly mean GSI values of females ranged from 6.36±0.69 to 15.02±1.33. The lowest mean GSI value was found in December and the highest GSI value was in October. From the histological observation of the ovary, early perinucleolar stage, late perinucleolar stage, yolk vesicle stage, yolk granule stage, pre-mature and mature stages were identified. The highest percentage (75%) of mature oocytes and peak breeding season were observed in October and the breeding season continues from October to November. These results will be helpful for fishery managers to impose adequate regulations for sustainable fishery management in Bangladesh.

Expression comparison and clinical significance of PD-L1 (22C3) and PD-L1 (SP142) in triple negative breast cancer

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).

Prognostic Utility of the Ki-67 Labeling Index in Follicular Thyroid Tumors: a 20-Year Experience from a Tertiary Thyroid Center

Follicular thyroid tumors pose a diagnostic challenge on the preoperative level, as the discrimination between follicular thyroid carcinoma (FTC) and adenoma (FTA) demands careful histopathological investigation. Moreover, prognostication of FTCs is mostly based on tumor size and extent of invasive properties, while immunohistochemical markers pinpointing high-risk cases are lacking. We have routinely established a Ki-67 labeling index for follicular thyroid tumors since 1999. To assess the potential value of Ki-67 as an adjunct tool to (1) correctly separate FTCs from FTAs and (2) help identify poor-prognosis FTCs, we collected histopathological and clinical data from 818 follicular thyroid tumors with a histological Ki-67 labeling index established in clinical routine practice (516 FTAs, 252 FTCs, and 50 follicular thyroid tumors of uncertain malignant potential (FT-UMPs)). The Ki-67 labeling index was higher in FTCs (mean 5.8%) than in FTAs (mean 2.6%) (P < 0.001), and a receiver operating characteristic curve analysis revealed a cut-off value of 4% to separate FTC from FTA with a sensitivity and specificity of 65% and 83%, respectively. Similarly, a Ki-67 labeling index above 4% was found to identify FTCs that later metastasized from clinically indolent FTCs with a sensitivity and specificity of 80% and 48%, respectively. Ki-67 constituted an independent predictor of future FTC metastases/recurrence and death of disease, and a value > 4% was a reliable prognostic marker within individual pT staging groups. We conclude that Ki-67 is a potentially valuable marker for the prognostication of FTCs, and future implementation in the histopathological assessments of follicular thyroid tumors could be beneficial if reproduced in international series.

Salvia hispanica L. seeds extract alleviate encephalopathy in streptozotocin-induced diabetes in rats: role of oxidative stress, neurotransmitters, DNA and histological indices

Context Diabetes mellitus (DM) is a metabolic disorder and may lead to cognitive dysfunctions. Objective The aim of this work is to evaluate the potency of Salvia hispanica L. seeds (S. hispanica L.) (chia seeds) petroleum ether extract in attenuating brain complications associated with streptozotocin (STZ) induced diabetes in rats. Materials and methods Phytochemical composition of the seeds extract, macro and micro elements, vitamins, protein, carbohydrate and caloric values were estimated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight (b.wt)). Glibenclamide as a reference drug was also evaluated. The biochemical evaluation was done by measuring levels of glucose, insulin, α- amylase, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), dopamine (DA), serotonin (5-HD), noradrenaline (NE), acetylcholinesterase (AchE), tumour necrosis factor-α (TNF-α), DNA fragmentation pattern and the histopathological profile of the brain hippocampus region. Results Gas chromatography/mass spectrometry (GC/MS) analysis revealed the presence of twenty-five fatty acid esters and twenty-two compounds. Column chromatography led to the isolation of nine compounds. Treatment with the seeds extract revealed improvement of the measured parameters with variable degrees. Conclusion Chia seeds extract succeeded to attenuate the neurodegeneration in diabetic rats. Thereafter, it had a therapeutic effect and could be potentially used as a new dietary supplement against diabetic encephalopathy.

Tumour budding in colorectal carcinoma: Association with other histopathological prognostic parameters

Colorectal carcinoma (CRC) is the third leading cancer in India. Pathologists play a crucial role in assessing stage, analyzing surgical margins and documenting the histopathologic prognostic parameters. Tumour budding is one such prognostic parameter, defined as single cells or small groups of tumour cells (up to 4 cell clusters) at the invasive front of the tumour. The aim of this study is to examine the association of tumour budding with other histopathological prognostic parameters in patients with colorectal carcinoma.TheHematoxylin &amp; Eosin (H &amp;E) stained slides of 52 histopathologically diagnosed CRC resection specimens were reviewed and tumour budding (BD) was assessed into four grades under 200x power. Other histopathological prognostic parameters like tumour size, site, grade, laterality, lymphovascular invasion, perineural invasion, T and N stage were analyzed using descriptive statistics and Chi-square test with Software SPSS version 23.A higher BD score is seen to be more often associated with grade 3 tumour morphology, presence of perineural invasion, tumour size of 5cm or more and tumours located in the sigmoid colon or rectum. No association of tumour budding is seen with TIL’s or tumour of size &amp;#60; 5cm.Tumour budding is a practical and significant histological index for identification of high malignant potential and poor outcome in CRC patients with rectal or sigmoid colon location, size more than 5cm, perineural invasion and higher histological grade. Tumour budding may help identify patients who need a more intensive postoperative follow up and the possibility of adjuvant therapy.

Histologic Remission (NANCY Index) is Superior to Endoscopic Mucosal Healing in Predicting Relapse Free Survival in Patients With Ulcerative Colitis in Clinical and Endoscopic Remission.

Histologic activity is recognized as an important predictor of relapse in ulcerative colitis (UC) patients. Current treatment targets aim at mucosal healing; however, many patients continue to have histologic activity. The aim was to assess histologic activity using the validated Nancy histologic index (NHI) score as a predictor of future relapse amongst UC patients in endoscopic and clinical remission. In this retrospective cohort study, UC patients in clinical and endoscopic remission at a single tertiary center between 2015 and 2018, who underwent a surveillance colonoscopy were included. Clinical remission was defined by partial Mayo score (MSp) <2, and endoscopic remission was defined by Mayo endoscopic subscore (MES) ≤1. Histologic remission was defined by NHI <2. Predictive factors associated with the primary endpoint of clinical relapse were analyzed. A total of 74 of 184 UC patients were included in the study. Amongst this cohort, 33 patients (45%) demonstrated histologic activity (NHI >1) at enrollment. The median follow-up time was 42 months (interquartile range: 26 to 63 mo) with median relapse free period of 30 months (interquartile range: 18 to 48 mo). Kaplan-Meier analysis demonstrated patients with MES 0 ( P =0.02) and histologic remission ( P <0.0001) had significantly longer relapse free survival. On multivariate analysis only histologic activity remained an independent risk factor of future clinical relapse (hazard ratio: 4.36, confidence interval: 1.68-11.27, P =0.002). Histologic remission using the NHI independently predicts significantly longer relapse free survival and may be a superior therapeutic target than endoscopic remission.

Growth, fatty acid composition, immune-related gene expression, histology and haematology indices of Penaeus vannamei fed graded levels of Antarctic krill meal at two different fishmeal concentrations

An eight-week feeding trial was conducted to investigate the effect of dietary krill meal inclusion in diets with moderate (12%) and low (6%) fishmeal concentrations for Penaeus vannamei. Inasmuch, eight iso‑nitrogenous and isolipidic diets were formulated to contain 36% crude protein and 5.5% crude lipid. In the moderate-fishmeal diets, krill meal was included at 0, 2, 4 and 6% (called FK12:0, FK12:2, FK12:4 and FK12:6, respectively), likewise in the low-fishmeal diets, krill meal was included at the same concentrations of 0–6% (called FK6:0, FK6:2, FK6:4 and FK6:6, respectively). Shrimp with a starting body weight of 0.55 ± 0.02 g were stocked at 22 animals per tank of 350 l capacity and fed three times daily. Results revealed that dietary krill meal and fish meal inclusion levels significantly increased growth performance (P < 0.05)and there was no significant effect on interaction between fishmeal and krill meal levels. Shrimp fed 6% krill meal diet had the highest final body weight of 11.61 g, weight gain of 11.05 g, weight gain % of 1969.38%, specific growth rate of 5.41%/d and yield of 229.42 g/tank. The weight gain % and SGR showed non significant difference between 4 and 6% krill meal containing groups. Dietary change did not affect feed conversion ratio, protein efficiency ratio and apparent protein utilization(P > 0.05). Survival was significantly increased in the groups containing 6 and 4% krill meal diets compared to 0% krill meal diet (P < 0.05). Inclusion levels of krill meal showed non-significant differences in post-fed body composition except for crude lipid and crude fibre content. Fishmeal inclusion levels showed significant (P < 0.05) variation in C14:0, C16:0, C18:0, C16:1,C18:1n-9, C18:2n-6, C22:6n-3, n-3/n-6 ratio, whereas krill meal inclusion levels showed significant variation in the all n-3 fatty acids only. Immune-related gene expression was significantly (P < 0.05) upregulated in the shrimp fed high fishmeal diets (12%) for all the analyzed genes ProPhenoloxidase (ProPO), ProPhenoloxidase activating enzyme (PPAE), Serine Protease (SP), β-1, 3-glucan-binding protein (BGBP), Superoxide dismutase (SOD), and Hemocyanin (HC). The dietary change led to a significant difference in both histology and haematology parameters (P < 0.05). The results inferred that krill meal could be used as a potential functional feed ingredient in Penaeus vannamei.The present study suggested beneficial effects of krill meal in shrimp diets. The levels of fishmeal inclusion (12 and 6%) also showed significant (P < 0.05) variations in various growth performance parameters. It is plausible that an inclusion level of 4% is the minimum for a measurable difference in growth performance.

PICaSSO virtual electronic chromendoscopy accurately reflects combined endoscopic and histological assessment for prediction of clinical outcomes in ulcerative colitis.

Background and AimsA composite endoscopic‐histologic remission is increasingly explored as an important endpoint in ulcerative colitis (UC). We investigated combined endoscopic‐histologic remission for predicting clinical outcomes at 12 months compared with endoscopic remission alone using the high definition virtual chromoendoscopy (VCE) Paddington International virtual ChromoendoScopy ScOre (PICaSSO) and histology scores.MethodsUlcerative colitis patients, prospectively enrolled from 11 international centres, underwent VCE with targeted biopsies and followed up for 12 months. Endoscopic activity was assessed by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index Severity (UCEIS) followed by VCE‐PICaSSO. Robarts Histopathological Index|Robarts Histological index≤3 without neutrophils in mucosa, and Nancy Histological index (NHI)≤ 1 were used to define histologic remission. Combined endoscopic‐histologic remission was compared with endoscopic remission alone by Cox proportional hazards model and by two‐ and three‐proportion analysis using pre‐specified clinical outcomes.Results307 patients were recruited and 302 analysed. There was no difference in survival without specified clinical outcomes between PICaSSO defined endoscopic remission alone and endoscopic plus histologic remission in the rectum (HR 0.42, 95%CI 0.16‐1.11 and HR 1.03, 95%CI 0.42‐2.52 for Robarts Histological index and NHI respectively) at 12 months. There was however a significant survival advantage without specified clinical outcome events for UCEIS combined with histology compared with UCEIS alone (HR 0.30, 95%CI 0.12‐0.75, p = 0.02) at 12 months (but not combined with NHI). For MES there was no advantage for predicting specified clinical outcomes at 12 months for endoscopy alone versus endoscopy plus histology, but there were differences in two and three proportion analysis at 6 months.ConclusionEndoscopic remission by VCE‐PICaSSO alone was similar to combined endoscopic and histologic remission for predicting specified clinical outcomes at 12 months. Larger studies with specific therapeutic interventions are required to further confirm the findings.

Reproducibility of the electronic chromoendoscopy PICaSSO score (Paddington International Virtual ChromoendoScopy ScOre) in ulcerative colitis using multiple endoscopic platforms: a prospective multicenter international study (with video)

Endoscopic and histologic remission (HR) are key therapeutic targets in the management of ulcerative colitis (UC). The aim of this study was to evaluate the reproducibility of the Paddington International virtual ChromoendoScopy ScOre (PICaSSO), a virtual chromoendoscopy score originally validated by use of the iSCAN platform, with the narrow-band imaging (NBI), linked-color imaging (LCI), and blue-laser imaging (BLI) platforms. We evaluated endoscopic activity using the Mayo Endoscopic Score (MES), the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and PICaSSO in 159 UC patients (78 NBI and 81 BLI/LCI) who underwent colonoscopy in 2 tertiary referral centers. HR was defined by the Robarts Histopathology Index (RHI) and the Nancy Histologic Index (NHI). Receiver operating characteristic curves were plotted to evaluate endoscopic scores for the prediction of HR. Intraclass correlation coefficients (ICC) between endoscopists were evaluated. PICaSSO had an ICC of 0.825 when the NBI and BLI/LCI cohorts were combined, higher than MES and UCEIS. The correlation between PICaSSO and RHI and NHI was 0.83 and 0.79 in the NBI cohort and between 0.63 and 0.65 in LCI/BLI. In the NBI cohort, the accuracy of MES, UCEIS, and PICaSSO was 0.936, 0.897, and 0.808 for HR measured by RHI and 0.897, 0.885, and 0.821 by NHI, respectively. In the BLI/LCI cohort, the accuracy of MES, UCEIS, LCI PICaSSO and BLI PICaSSO was 0.765, 0.778, 0.827, and 0.79 to predict HR with RHI and NHI, respectively. The PICaSSO score can be consistently and accurately reproduced with NBI and LCI/BLI and therefore can be applied to all virtual electronic chromoendoscopy platforms.

PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system

Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply...

Abstract P1-03-01: Heterogeneity between core needle biopsy and primary tumor tissue in early breast cancer patients: Comparison of intrinsic subtypes after different treatment regimes

Abstract Background: All initial therapeutic decisions in early breast cancer are commonly based on the expression profiles of estrogen (ER), progesterone (PR) and the human epidermal growth factor 2 (HER2) receptors. However, breast cancer is a very heterogeneous disease, and receptor changes were manifold reported during progression. Only little data is known about receptor changes after upfront therapy. Here, we compared receptor expression profiles between core needle biopsy (CNB) tissue and primary tumor tissue after different treatment regimes. Methods: In a German single center study, we retrospectively analyzed 248 breast cancer patients during primary treatment regime between 2014 and 2020. Patients had either neoadjuvant chemotherapy, neoadjuvant endocrine therapy or no upfront therapy. Tumor material was obtained by core needle biopsy (CNB) at primary diagnosis and during primary oncological surgery of the axilla and breast. Analysis of histological subtype, grading, Ki67 index and expression profiling of ER, PR, HER2, was performed using formalin-fixed, paraffin-embedded (FFPE) specimens. Immunohistochemical examination was performed according to the ASCO/CAP guidelines using the Ventana-platform. Tumors were grouped into different intrinsic subtypes according to the international St. Gallen classification in either Luminal A, Luminal B, HER2-enriched or triple negative. 35 patients were excluded because the intrinsic subtype was not specified in the CNB and final postoperative specimen, therefore 213 patients were included in the primary analysis. Results: In the primary analysis (n=213), median age was 53 years (IQR 43 - 64). Based on the initial CNB receptor profile 105 (49%) patients had a Luminal A carcinoma, 46 (22%) patients had a Luminal B HER2 negative carcinoma, 22 (10%) patients had a Luminal B HER2 positive carcinoma, 6 (3%) patients had a HER2 enriched carcinoma and 33 (16%) patients had a triple negative carcinoma. In the primary analysis 84 (39%) patients had neoadjuvant chemotherapy, 48 (23%) patients had neoadjuvant endocrine therapy and 81 (38%) patients had no upfront therapy. Overall, 77 (36%) patients had an intrinsic subtype change between CNB and definitive surgical treatment, 139 (64 %) patients had no subtype change. There were 44 (52%) changes after neoadjuvant chemotherapy, 17 (35%) changes after neoadjuvant endocrine therapy and 16 (20%) subtype changes after no upfront therapy (p&amp;lt;0.0001 for the effect of neoadjuvant chemotherapy). ER receptor status changed in 5 (6%) patients after neoadjuvant chemotherapy, 6 (13%) changes were observed after neoadjuvant endocrine therapy and 2 (2%) ER changes occurred after no upfront therapy. Concerning the PR receptor there were 23 (27%) receptor changes after neoadjuvant chemotherapy, 17 (35%) changes after neoadjuvant endocrine therapy and 9 (11%) changes after no upfront therapy (p&amp;lt;0.0001 for the effect of neoadjuvant endocrine therapy). Regarding the HER2 receptor, there were 18 (21%) receptor status changes after neoadjuvant chemotherapy, 2 (4%) changes after neoadjuvant endocrine therapy and 2 (2%) subtype changes after no upfront therapy (p=0.0001 for the effect of neoadjuvant chemotherapy).Neoadjuvant chemotherapy led significantly more often to a decrease of HER2 expression, compared to neoadjuvant endocrine therapy or no upfront therapy. Conclusions: Our results imply the high frequency of intrinsic subtype changes after neoadjuvant therapy. Subtype changes should be taken into account for an optimal and individual treatment. Further research needs to be conducted to investigate whether an individual treatment decision based on the receptor profile after primary treatment might improve clinical outcome of breast cancer patients. Citation Format: Laura Weydandt, Anne Kreklau, Ivonne Nel, Lars-Christian Horn, Bahriye Aktas. Heterogeneity between core needle biopsy and primary tumor tissue in early breast cancer patients: Comparison of intrinsic subtypes after different treatment regimes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-03-01.

Baseline Amide Proton Transfer Imaging at 3T Fails to Predict Early Response to Induction Chemotherapy in Nasopharyngeal Carcinoma.

BackgroundEarly identification of nasopharyngeal carcinoma (NPC) patients with high risk of failure to induction chemotherapy (IC) would facilitate prompt individualized treatment decisions and thus reduce toxicity and improve overall survival rate. This study aims to investigate the value of amide proton transfer (APT) imaging in predicting short-term response of NPC to IC and its potential correlation with well-established prognosis-related clinical characteristics.Methods and MaterialsA total of 80 pathologically confirmed NPC patients receiving pre-treatment APT imaging at 3T were retrospectively enrolled. Using asymmetry analysis, APT maps were calculated with mean (APTmean), 90th percentile (APT90) of APT signals in manually segmented NPC measured. APT values were compared among groups with different histopathological subtypes, clinical stages (namely, T, M, N, and overall stages), EBV-related indices (EBV-DNA), or responses to induction chemotherapy, using Mann–Whitney U test or Kruskal–Wallis H test.ResultsNPC showed significantly higher APTmean than normal nasopharyngeal tissues (1.81 ± 0.62% vs.1.32 ± 0.56%, P <0.001). APT signals showed no significant difference between undifferentiated and differentiated NPC subtypes groups, different EBV-DNA groups, or among T, N, M stages and overall clinical stages of II, III, IVA and IVB (all P >0.05). Similarly, baseline APT-related parameters did not differ significantly among different treatment response groups after IC, no matter if evaluated with RECIST criteria or sum volumetric regression ratio (SVRR) (all P >0.05).ConclusionNPC showed significantly stronger APT effect than normal nasopharyngeal tissue, facilitating NPC lesion detection and early identification. However, stationary baseline APT values exhibited no significant correlation with histologic subtypes, clinical stages and EBV-related indices, and showed limited value to predict short-term treatment response to IC.

Supplementing Sulfate-Based Alginate Polysaccharide Improves Pacific White Shrimp (Litopenaeus vannamei) Fed Fishmeal Replacement with Cottonseed Protein Concentrate: Effects on Growth, Intestinal Health, and Disease Resistance

Sulfate-based alginate polysaccharide (SAP) is a novelty marine prebiotic. To investigate the beneficial effects of SAP in Pacific white shrimp (Litopenaeus vannamei) fed low-fishmeal diets, six diets (whole fishmeal group: FM; fishmeal replacement with cottonseed protein concentrate and SAP supplementary groups: SAP0, SAP1, SAP2, SAP3, and SAP4) were formulated and fed shrimp for 56 days. The results showed that SAP2 and SAP3 groups reached the best weight gain and specific growth rate ( P &lt; 0.05 ). In serum, the activities of lysozyme and acid phosphatase showed the trend of firstly increased and then decreased ( P &lt; 0.05 ). In the gut, the highest activities of trypsin, lipase, and amylase were found in SAP2 and SAP3 groups ( P &lt; 0.05 ); the histological indexes gradually improved with SAP levels increased ( P &lt; 0.05 ); sequencing of microbiota revealed that the composition and structure of microbiota have been improved, especially in the decreasing abundance of Vibrio, Pseudoalteromonas, and Candidatus Bacilloplasma at genus level. Besides, transcriptomics revealed a degree of similarity in differential gene expression patterns in shrimp; the comparison of RNA-Seq and qRT-PCR verified that SAP improved antioxidant and immunity in shrimp. The challenge revealed that SAP strengthened the resistance against Vibrio parahaemolyticus. Totally, the supplementary SAP to low-fishmeal diets improved growth, intestinal health, and disease resistance in shrimp. Based on the polynomial curve analysis of specific growth rate among SAPs groups, the optimum SAP supplementary level was 1.91%.

Molecular mechanism of the TGF‑β/Smad7 signaling pathway in ulcerative colitis.

Aberrant TGF-β/Smad7 signaling has been reported to be an important mechanism underlying the pathogenesis of ulcerative colitis. Therefore, the present study aimed to investigate the effects of a number of potential anti-colitis agents on intestinal epithelial permeability and the TGF-β/Smad7 signaling pathway in an experimental model of colitis. A mouse model of colitis was first established before anti-TNF-α and 5-aminosalicyclic acid (5-ASA) were administered intraperitoneally and orally, respectively. Myeloperoxidase (MPO) activity, histological index (HI) of the colon and the disease activity index (DAI) scores were then detected in each mouse. Transmission electron microscopy (TEM), immunohistochemical and functional tests, including Evans blue (EB) and FITC-dextran (FD-4) staining, were used to evaluate intestinal mucosal permeability. The expression of epithelial phenotype markers E-cadherin, occludin, zona occludens (ZO-1), TGF-β and Smad7 were measured. In addition, epithelial myosin light chain kinase (MLCK) expression and activity were measured. Anti-TNF-α and 5-ASA treatments was both found to effectively reduce the DAI score and HI, whilst decreasing colonic MPO activity, plasma levels of FD-4 and EB permeation of the intestine. Furthermore, anti-TNF-α and 5-ASA treatments decreased MLCK expression and activity, reduced the expression of Smad7 in the small intestine epithelium, but increased the expression of TGF-β. In mice with colitis, TEM revealed partial epithelial injury in the ileum, where the number of intercellular tight junctions and the expression levels of E-cadherin, ZO-1 and occludin were decreased, all of which were alleviated by anti-TNF-α and 5-ASA treatment. In conclusion, anti-TNF-α and 5-ASA both exerted protective effects on intestinal epithelial permeability in an experimental mouse model of colitis. The underlying mechanism may be mediated at least in part by the increase in TGF-β expression and/or the reduction in Smad7 expression, which can inhibit epithelial MLCK activity and in turn reduce mucosal permeability during the pathogenesis of ulcerative colitis.

Impact of Diagnostic Delays on Lung Cancer Survival Outcomes: A Population Study of the US SEER-Medicare Database.

Time from diagnosis to treatment has been associated with worse survival outcomes in non-small-cell lung cancer (NSCLC). However, little is known about the impact of delay in time to diagnosis. We aimed to evaluate the impact of time from radiographic suspicion to histologic diagnosis on survival outcomes using the US SEER-Medicare population database. We identified patients from the SEER-Medicare data set diagnosed with any stage NSCLC between January 1, 2011, and December 31, 2015, who received stage-appropriate treatment and had a computed tomography scan within 1 year of diagnosis. Time to confirmation was determined as the interval between most recent computed tomography imaging and date of histologic diagnosis. Our primary outcome was overall survival (OS). In total, 10,824 eligible patients were identified. The median time to confirmation was 20 (range 0-363) days. Using multivariate Cox regression models, longer time to confirmation was associated with improved OS in all comers driven by stage IV patients after adjustment for age, sex, diagnosis year, histology, and comorbidity index. In a separate landmark analysis excluding patients deceased within 6 months of diagnosis, the association between time to diagnosis and survival was no longer evident. Time to confirmation of NSCLC was inversely associated with OS in this US SEER population study. This association was lost when patients deceased within 6 months of diagnosis were excluded, suggesting that retrospective registry-claims databases may not be the optimal data source to study time to diagnosis as a quality metric because of the unaccounted confounding effects of tumor behavior. Prospective evaluations of clinically enriched data sources may better serve this purpose.