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Background: Diagnosis of kidney transplant rejection currently relies on manual histopathological assessment, which is subjective and susceptible to interobserver variability, leading to limited reproducibility. We aim to develop a deep learning system for automated assessment of whole-slide images (WSIs) from kidney allograft biopsies to enable detection and subtyping of rejection and to predict the prognosis of rejection. Method: We collected H&E-stained WSIs of kidney allograft biopsies at 400x magnification from January 2015 to September 2023 at two hospitals. These biopsy specimens were classified as T cell-mediated rejection, antibodymediated rejection, and other lesions based on the consensus reached by two experienced transplant pathologists. To achieve feature extraction, feature aggregation, and global classification, we employed multi-instance learning and common convolution neural networks (CNNs). The performance of the developed models was evaluated using various metrics, including confusion matrix, receiver operating characteristic curves, the area under the curve (AUC), classification map, heat map, and pathologist-machine confrontations. Results: In total, 906 WSIs from 302 kidney allograft biopsies were included for analysis. The model based on multi-instance learning enables detection and subtyping of rejection, named renal rejection artificial intelligence model (RRAIM), with the overall 3-category AUC of 0.798 in the independent test set, which is superior to that of three transplant pathologists under nearly routine assessment conditions. Moreover, the prognosis models accurately predicted graft loss within 1 year following rejection and treatment response for rejection, achieving AUC of 0.936 and 0.756, respectively. Conclusion: We first developed deep-learning models utilizing multi-instance learning for the detection and subtyping of rejection and prediction of rejection prognosis in kidney allograft biopsies. These models performed well and may be useful in assisting the pathological diagnosis. [ABSTRACT FROM AUTHOR]

Background. There are no specific morphological signs for sporadic multiglandular disease (MGD) in primary hyperparathyroidism (PHPT).The aim of the study. To study the structure of the morphological substrate of primary, secondary and tertiary hyperparathyroidism and to assess the effectiveness of morphological criteria in the diagnosis of sporadic multiglandular disease in primary hyperparathyroidism. Methods. The study included 69 patients; 18 patients with PHPT and sporadic multiglandular disease (npreparation = 31) formed the main group, 51 patients (npreparations = 104) – the comparison group. The comparison group was divided into 3 subgroups: 1) patients with PHPT and solitary parathyroid gland (PTG) lesions – 26 patients (npreparations = 26); 2) patients with secondary hyperparathyroidism (SHPT) – 15 patients (npreparations = 48); 3) patients with tertiary hyperparathyroidism (TGPT) – 10 patients (npreparations = 30). Results. The morphological structure of the comparison groups is homogeneous: group 1 is represented by parathyroid adenoma (26 (100 %)), groups 2 and 3 – by hyperplasia (48 (100 %) and 30 (100 %), respectively). Most of the PTG specimens of the main group are represented by hyperplasia (25 (80 %)), and in 1/5 cases – by adenomas (6 (19.4 %)). Sporadic multiglandular disease in PHPT was characterized by a predominant frequency of detecting the absence of a capsule and a rim of unchanged tissue, as well as the presence of adipocytes (pχ2 < 0.01). Components of the PTG morphological structure make it possible to identify changes specific to the sporadic multiglandular disease in PHPT, with a diagnostic efficiency of 76.5–90.3 %. Conclusion. Sporadic multiglandular disease in any clinical variant of hyperparathyroidism is characterized by a high prevalence of hyperplasia – 80 % in PHPT and 100 % in SHPT and TGPT. The following morphological criteria for sporadic multiglandular disease in PHPT have been established: the presence of adipocytes in the PTG parenchyma (diagnostic efficiency (DE) – 90 %)); absence of a capsule (DE = 78 %) and a rim of unchanged gland tissue (DE = 76 %).

Mersha Asfaw,1 Menur Senbit,2 Mohammed Yesuf,1 Melkie Dagnaw,3 Girma Birhan,1 Anmaw Shite Abat,1 Saddam Mohammed Ibrahim1 1Department of Veterinary Pathobiology, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia; 2Department of Veterinary Epidemiology and Public Health, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia; 3Department of Veterinary Clinical Studies, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Saddam Mohammed Ibrahim, Tel +251 918150427, Email sadimohamed6@gmail.comIntroduction: In this study we aimed to provide preliminary evidence on the safety and efficacy of the currently used ovine pasteurellosis vaccine in Ethiopia using clinical and pathological endpoints.Methods: Twenty, conventionally reared, apparently healthy, seronegative male lambs, were randomly classified into two groups of 10 animals as “vaccinated-challenged” and ”unvaccinated-challenged controls”. The first group received 1 mL of the licensed Pasteurella multocida biotype A based vaccine subcutaneously while the second group received phosphate-buffered saline as a placebo. Following vaccination, lambs were monitored for one month for potential vaccine adverse reactions. Five weeks postvaccination, all lambs were immunosuppressed using dexamethasone, and intratracheally challenged with 5.2× 109 CFU/mL live Mannheimia haemolytica A1 (clinical isolates). Then, all lambs were followed up for eight days for clinical examination and necropsied on the ninth day postchallenge for pathological investigation.Results: There were no safety issues recorded during the study. In terms of clinical signs, lambs developed fever, depression, mucoid bilateral oculonasal discharge, coughing and sneezing regardless of their vaccination status. Fisher’s exact test between vaccination status and each clinical sign showed a statistically insignificant association (p> 0.05). The main pathological findings in both groups were pulmonary congestion, atelectasis, emphysema, and suppurative bronchopneumonia. Consolidation lung lesion score of +1 (5/10 of vaccinated, 6/10 of unvaccinated) and +2 (3/10 of vaccinated, 4/10 of unvaccinated) were recorded in a statistically indifferent manner among both vaccinated and nonvaccinated groups (p> 0.05).Discussion and Conclusion: Collectively, the results suggested that the vaccine posed no safety concern and presumably lacks protective efficacy against local isolates. However, the study did not analyze antibody titer and their functionality using serum bactericidal assays. Further confirmatory studies could provide more evidence on the vaccine efficacy. Safety should further be assessed in a field setting involving a large number of animals to enable detection of rare vaccine adverse events.Keywords: ovine pasteurellosis, pathological assessment, vaccine efficacy, vaccine safety

Due to their increased detection pancreatic cystic space-occupying lesions are becoming increasingly relevant in the clinical routine and represent a morphologically and biologically heterogeneous and thus clinically demanding as well as potentially (pre)malignant entity. As a result, recommendations for the diagnostics and treatment of pancreatic cystic tumors have now been incorporated into the current German S3 guidelines on pancreatic cancer. The diagnostics of pancreatic cystic space-occupying lesions are based on the following three elements: collection of relevant clinical information, performance of high-resolution imaging procedures and if diagnostic uncertainty persists, puncture diagnostics. Differentiated diagnostics are of essential importance as these represent the basis for an adequate treatment decision. Pancreatic cystic lesions with a relevant risk of malignant transformation, e.g., main duct intraductal papillary mucinous neoplasms (IPMN), followed by mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and generally pancreatic cystic lesions with risk factors independent of the entity, should be resected, whereas a differentiated and individualized approach is necessary, especially for branch-duct IPMNs. The serous cystic neoplasms (SCN) have no malignant potential and do not require any treatment if they are asymptomatic. Important principles in surgery of pancreatic cancer, such as adequate surgical resection taking oncological standards into account and standardized appropriate histopathological processing of the specimens as well as intraoperative frozen section analysis also play an important role in pancreatic cystic space-occupying lesions. An annual follow-up seems to be meaningful, especially for IPMNs. [ABSTRACT FROM AUTHOR]

Introduction:This study aimed to evaluate patients who presented with eyelid tumour and to evaluate the masses pathologically.Methods:Between March 1, 2016- April 1, 2019, 2019, age, gender, eyelid side, pathological evaluation results and surgical margin status of the patients who presented to our clinic with eyelid mass were evaluated.Results:During the study period, 212 patients with a mean age of 55±16 years (range, 15-85 years) who underwent surgery because of an eyelid mass were included in the study. Among these patients, 78 (37.8%), 74 (35.9%) and 54 (26.2%) underwent surgery of the right, left and both eyelids, respectively, whereas 55 (26.9%), 128 (62.7%) and 21 (10.2%) underwent surgery of the lower, upper and both lower and upper eyelids, respectively. A total of 376 eyelid mass surgeries were performed. Among these masses, 371 (98.6%) were benign and 5 (1.3%) were malignant. Regarding pathological types of benign masses, 71 (19.1%) were seborrheic keratosis, 70 (18.8%) were squamous papilloma, 53 (14.21%) were fibroepithelial polyps, 52 (14.2%) were xanthelasma, 35 (9%) were intradermal nevus, 22 (5.9%) were epidermoid cyst, 14 (3.8%) were verruca vulgaris and 51 (13.7%) were different types of tumours. Five patients were diagnosed with malignant eyelid tumours; three of them had basal cell carcinoma, one had squamous cell carcinoma and one had malignant melanoma.Conclusion:Although eyelid tumours are mostly benign tumours, malignant tumours may be present in some cases. Pathological evaluation of valve masses obtained surgically is important to determine the prognosis of patients.

Assessment of the estrous cycle of mature female mammals is an important component of verifying the efficacy and safety of drug candidates. The common pathological approach of relying on expert observation has several drawbacks, including laborious work and inter-viewer variability. The recent advent of image recognition technologies using deep learning is expected to bring substantial benefits to such pathological assessments. We herein propose 2 distinct deep learning-based workflows to classify the estrous cycle stage from tissue images of the uterine horn and vagina, respectively. These constructed models were able to classify the estrous cycle stages with accuracy comparable with that of expert pathologists. Our digital workflows allow efficient pathological assessments of the estrous cycle stage in rats and are thus expected to accelerate drug research and development.

Background: Diagnosis of kidney transplant rejection currently relies on manual histopathological assessment, which is subjective and susceptible to inter-observer variability, leading to limited reproducibility. We aim to develop a deep learning system for automated assessment of whole-slide images (WSIs) from kidney allograft biopsies to enable detection and subtyping of rejection and to predict the prognosis of rejection., Method: We collected H&E-stained WSIs of kidney allograft biopsies at 400x magnification from January 2015 to September 2023 at two hospitals. These biopsy specimens were classified as T cell-mediated rejection, antibody-mediated rejection, and other lesions based on the consensus reached by two experienced transplant pathologists. To achieve feature extraction, feature aggregation, and global classification, we employed multi-instance learning and common convolution neural networks (CNNs). The performance of the developed models was evaluated using various metrics, including confusion matrix, receiver operating characteristic curves, the area under the curve (AUC), classification map, heat map, and pathologist-machine confrontations., Results: In total, 906 WSIs from 302 kidney allograft biopsies were included for analysis. The model based on multi-instance learning enables detection and subtyping of rejection, named renal rejection artificial intelligence model (RRAIM), with the overall 3-category AUC of 0.798 in the independent test set, which is superior to that of three transplant pathologists under nearly routine assessment conditions. Moreover, the prognosis models accurately predicted graft loss within 1 year following rejection and treatment response for rejection, achieving AUC of 0.936 and 0.756, respectively., Conclusion: We first developed deep-learning models utilizing multi-instance learning for the detection and subtyping of rejection and prediction of rejection prognosis in kidney allograft biopsies. These models performed well and may be useful in assisting the pathological diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ye, Xia, Yang, Luo, Tang, Li, Han, Xie, Ren and Na.)

Background: This study aimed to assess the clinical effect of the pathological axillary assessment method in breast cancer without clinical lymph node metastasis. Methods: Data of patients with clinically node-negative breast cancer were retrospectively reviewed. The study period was divided into early (January 2000–July 2007) and late (August 2007–December 2014) periods based on the pathological assessment method used (single-sectional and detailed multi-sectional lymph node processing). In the late period, lymph nodes were evaluated at six levels including immunohistochemistry on each 1.5–2 mm interval section. The axillary diagnostic accuracy and role of chemotherapy were assessed. Results: In 1698 patients, 27 isolated tumor cells (ITCs), 39 micrometastases, and 205 macrometastases were noted. The sensitivity for pathological N0 diagnosis was dependent on clinical T stage, Tis (97.8%), T1 (83.0%), T2 (74.2%), T3 (54.5%), and T4 (63.6%). ITCs and micrometastases were detected only in the late period, and 84.7% and 91.6% of cases in the early and late period, respectively, did not have macrometastases. The 5-year disease-free interval (DFI) rates were 95.2% in node-negative cases, 98.4% in ITCs/micrometastases, and 91.4% in macrometastases (P < 0.001). In multivariate analysis, the predictor for DFI was estrogen receptor negativity (P = 0.013). Chemotherapy did not improve DFI in patients with node-positive breast cancer. Conclusions: The detailed multi-sectional pathological assessment of axillary lymph nodes detected ITCs and micrometastases. Implementation of chemotherapy should not be based on the minimal nodal metastasis and this type of serially nodal sectioned processing had little clinical significance. [ABSTRACT FROM AUTHOR]

Abstract Background Targeted therapy for non-small cell lung cancer is histology dependent. However, histological classification by routine pathological assessment with hematoxylin-eosin staining and immunostaining for poorly differentiated tumors, particularly those from small biopsies, is still challenging. Additionally, the effectiveness of immunomarkers is limited by technical inconsistencies of immunostaining and lack of standardization for staining interpretation. Results Using gene expression profiles of pathologically-determined lung adenocarcinomas and squamous cell carcinomas, denoted as pADC and pSCC respectively, we developed a qualitative transcriptional signature, based on the within-sample relative gene expression orderings (REOs) of gene pairs, to distinguish ADC from SCC. The signature consists of two genes, KRT5 and AGR2, which has the stable REO pattern of KRT5 > AGR2 in pSCC and KRT5

Purpose Tumor regression grade (TRG) has been widely used in gastrointestinal carcinoma to assess pathological responses to neoadjuvant chemotherapy (NCT). There are various standards without a consensus, and it is still unclear which kind of system has better predictive value. This study aims to investigate and compare the predictive ability of the Mandard and Becker TRGs in patients with locally advanced gastric cancer. Materials and Methods A total of 290 patients with locally advanced gastric adenocarcinoma who underwent NCT and curative surgery were studied. Survival analysis for overall survival (OS) and disease-free survival (DFS) were based on the Kaplan-Meier method and Cox proportional hazards method. Predictive values of TRGs and models were assessed by time-dependent receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), nomogram, and calibration curve. Results In multivariable analysis, the Mandard TRG was associated with OS (hazard ratio [HR], 1.806; p=0.026) and DFS (HR, 1.792; p=0.017). The Becker TRG was also related to OS (HR, 1.880; p=0.014) and DFS (HR, 1.919; p=0.006). The Mandard and Becker TRG AUCs for 5-year survival were 0.72 and 0.71, respectively. The whole models showed an increased predictive value, with AUCs of 0.85 and 0.86, respectively. There was no significant difference between the two TRGs and two models. Conclusion TRG was an independent predictor for survival, and there was no significant difference between these two systems. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate patients who presented with eyelid tumour and to evaluate the masses pathologically. Methods: Between March 1, 2016- April 1, 2019, 2019, age, gender, eyelid side, pathological evaluation results and surgical margin status of the patients who presented to our clinic with eyelid mass were evaluated. Results: During the study period, 212 patients with a mean age of 55±16 years (range, 15-85 years) who underwent surgery because of an eyelid mass were included in the study. Among these patients, 78 (37.8%), 74 (35.9%) and 54 (26.2%) underwent surgery of the right, left and both eyelids, respectively, whereas 55 (26.9%), 128 (62.7%) and 21 (10.2%) underwent surgery of the lower, upper and both lower and upper eyelids, respectively. A total of 376 eyelid mass surgeries were performed. Among these masses, 371 (98.6%) were benign and 5 (1.3%) were malignant. Regarding pathological types of benign masses, 71 (19.1%) were seborrheic keratosis, 70 (18.8%) were squamous papilloma, 53 (14.21%) were fibroepithelial polyps, 52 (14.2%) were xanthelasma, 35 (9%) were intradermal nevus, 22 (5.9%) were epidermoid cyst, 14 (3.8%) were verruca vulgaris and 51 (13.7%) were different types of tumours. Five patients were diagnosed with malignant eyelid tumours; three of them had basal cell carcinoma, one had squamous cell carcinoma and one had malignant melanoma. Conclusion: Although eyelid tumours are mostly benign tumours, malignant tumours may be present in some cases. Pathological evaluation of valve masses obtained surgically is important to determine the prognosis of patients. [ABSTRACT FROM AUTHOR]

During clamping operation for minimally invasive intestinal surgery, patients often suffer from small intestine trauma. This phenomenon will lead to various complications, increase recovery time and cause pain for patients. In this paper, preliminary simulations of small intestine clamping operations in the minimally invasive surgery were made by conducting compression tests under different clamping stresses, durations and loading rates. A pathological grading system was designed after microscope observation to quantitatively evaluate the trauma of small intestine tissue. Results showed that different traumas: inflammatory cell infiltration, hyperemia, hemorrhage and rupture between serosa and muscularis, as well as villi destruction could be observed on the clamping sites of the small intestine tissue. When the clamping parameters (clamping stress, duration and loading rate) increased, the degree of the tissue trauma increased. There existed safe thresholds for clamping operations, at which severe trauma of small intestine tissues could be avoided in the clamping process. As the clamping parameters increased, the strain, that is the deformation of the small intestine tissue increased. The increase in the deformation would induce the aggravation of trauma degree. • Small intestine traumas under different clamping parameters were studied. • Pathological grading system was designed to quantitatively assess tissue damage. • Trauma degree was increasingly serious with the increasing clamping parameters. • Traumas were related to the variation of mechanical properties of soft tissue. • Safe thresholds were determined for prevention of severe trauma. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) (Oncotype DXVR ; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologicgenomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n¼322) and the RS<18 low-risk group (3.4%, n¼703), as well as between the AAMC high-risk group (22.8%, n¼230) and the RS>30 high-risk group (23.0%, n¼141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n¼739) and 24.2% for the high-risk group (n¼272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate differences in the histological features of rectal cancer between patients treated with preoperative chemoradiotherapy and those treated with preoperative chemotherapy. Area of residual tumor (ART) was also evaluated for its utility as a potential prognostic marker between them. Sixty‐eight patients with rectal cancer who underwent sphincter‐saving surgery were enrolled in this study. Of these, 39 patients received preoperative chemoradiotherapy (CRT group) and 29 patients received preoperative (neoadjuvant) chemotherapy (NAC group). Area of residual tumor was determined by using morphometric software. Tumors in the two groups were compared for differences in their histological features and clinical outcomes. Tumors in the CRT and NAC groups varied greatly with regard to their histological features after preoperative therapy. Tumors in the CRT group showed more marked fibrosis than those in the NAC group. The total ART were significantly smaller in tumors in the CRT group than those in the NAC group. However, in circumferential resection margin‐negative pathologic stage 0‐III cases, clinical outcomes were not statistically different between the CRT and NAC groups. Both ART and pathologic TNM classification were associated with clinical outcome in preoperative CRT and NAC groups, but Dworak regression grade and fibrotic change were not. Tumors in those undergoing preoperative CRT and NAC were shown to differ significantly in their histological features. Area of residual tumor‐based assessment may provide useful prognostic information, regardless of preoperative therapy. [ABSTRACT FROM AUTHOR]

Background: Tissue grasping damage often occurs in minimally invasive surgery, which would increase the postoperative recovery time and the risk of surgical complications. The purpose of this study was to evaluate the relationship between liver tissue trauma and compression stress magnitude and duration during tissue clamping operation. Methods: The clamping experiments of liver tissues in vivo were conducted by using a universal soft tissue mechanical testing machine under different clamping stress magnitudes and durations. The rabbit liver was used to simulate human liver. A minimally invasive surgery grasper was used in these tests to simulate the real tissue-surgical operation condition. A pathological grading system was created to quantitatively assess the trauma within the liver tissue. The hyperbolic regression models were utilized to predict the trauma degree of liver tissue. Findings: Obvious hyperemia, hemorrhage, hepatic capsule rupture and inflammatory cell infiltration appeared in the clamping sites of the liver. Assessment results indicated that the trauma degree increased nonlinearly with the increasing clamping stress and duration time. There exist safe thresholds, in which the severe trauma of the studied tissue can be avoided during grasping operation. Interpretation: The results could provide the safety margins and the trauma prediction models for surgeons during grasping and palpation tasks in minimally invasive surgery. [ABSTRACT FROM AUTHOR]

We explored clinicopathological features and treatment strategies for thoracic SMARCA4 -deficient undifferentiated tumor ( SMARCA4 -UT). Thoracic SMARCA4 -UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4 -UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4 -UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4 -UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4 -deficient tumors. SMARCA4 -deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4 -UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4 -deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4 -UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4 -UT should enlighten significance for various kinds of SMARCA4 -deficient tumors.

To the best of our knowledge, this is the first report of post-partum hemorrhage (PPH) caused by an occult abnormal artery detected shortly after delivery on pelvic angiography (PAG). Initially, a diagnosis of uterine atony was made because the apparent cause of hemorrhage was not detected via the usual obstetrical examination. An abnormal artery, however, was suspected on PAG and confirmed on pathology. This case suggests a novel cause of persistent PPH resistant to obstetric management. Obstetricians should be aware that an abnormal artery may cause PPH, and that radiology may be required for diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to analyze the influence of variations in clinical practice regarding the timing of surgery with short-course chemoradiotherapy with delayed surgery (SCRT-delay) for lower rectal cancer. Methods: A total of 171 patients with T3 N0-2 lower rectal cancer treated with SCRT-delay (25 Gy/10 fractions/5 days (S-1); days 1-10) were retrospectively evaluated. The median waiting period of 30 days was used as a discriminator (group A: waiting period, ≤30 days; group B: waiting period, ≥31 days). Preoperative treatment responses and oncological outcomes were analyzed. Results: The mean waiting periods for groups A and B were 24.4 ± 5.3 and 41.4 ± 12.3 days, respectively. There were no statistically significant differences between the two groups in any of the clinical variables. The clinicopathological outcomes were as follows: T downstaging (43.5 vs 37.2 %; p = 0.400), negative yp N (67.1 vs 75.6 %; p = 0.218), pCR (7.1 vs 1.2 %; p = 0.119). The 5-year local recurrence-free survival (89.3 vs 87.6 %; p = 0.956), the recurrence-free survival (82.2 vs 78.8 %; p = 0.662), and the overall survival (88.5 vs 84.4 %; p = 0.741), all of which were similar between the two groups. Conclusions: The longer waiting period did not increase the tumor downstaging and not improve the oncological outcomes for T3 lower rectal cancer treated with SCRT-delay. In addition, considering that the impaired leukocyte response occurred during the sub-acute period, any time after the sub-acute period (day 12) up to 30 days after radiotherapy would be a suitable waiting period. [ABSTRACT FROM AUTHOR]

Purpose: The tumor volume or extent measurement in radical prostatectomy (RP) specimens is time-consuming and technically difficult. We aimed at studying the independent prognostic value of tumor extent for biochemical progression-free following RP once it is controversial. Methods: This retrospective study was based on 305 consecutive patients submitted to RP. In whole-mount and totally embedded surgical specimens, tumor extent was evaluated with a point-count semi-quantitative method and correlated to several clinical and pathological variables. Biochemical progression was defined as PSA ≥ 0.2 ng/ml; time to progression-free outcome was studied using the Kaplan-Meier product-limit analysis and univariate and multivariate analyses using the Cox stepwise logistic regression. Results: More extensive tumors showed significantly higher preoperative PSA ( P < 0.01), higher clinical stage ( P = 0.03), higher positive surgical margins ( P < 0.01), higher pathological stage ( P < 0.01), and higher Gleason score on needle biopsies ( P < 0.01) and on surgical specimens ( P < 0.01). On univariate analysis, biochemical progression correlated with tumor extension ( P < 0.01), preoperative PSA ( P < 0.01), Gleason score on needle biopsies ( P = 0.02) and on surgical specimens ( P < 0.01), positive surgical margins ( P = 0.01), and pathological stage ( P = 0.01). There was no difference related to time of biochemical recurrence comparing less extensive with more extensive tumors ( P = 0.20). In multivariate analysis, tumor extent was not predictive of biochemical progression combined to any one of the variables studied ( P > 0.05). Conclusions: Tumor extent did not provide in our study additional predictive information for biochemical progression following RP beyond preoperative PSA, Gleason score, positive surgical margins, and pathological stage. [ABSTRACT FROM AUTHOR]

Budesonide is an anti-inflammatory drug of choice for treatment of ulcerative colitis which affects the rectum and a part of or the entire colon. Delivery of budesonide specifically to the colon would increase the efficacy of the drug and reduce the side-effects. The aim of this study was to develop an oral matrix system formulation for budesonide to deliver the major part of the drug to the colon for treatment of ulcerative colitis that has not been reported before. Directly compressed matrix tablets were prepared using different molecular weights of dextran and three ratios of drug-to-polymer. The physical properties of the tablets including weight variation, hardness, content uniformity, and release profile in HCl 0.1 N, phosphate buffer pH 7.4 and 6.8 containing 4% rat caecal and colonic contents were studied. The efficacy of the desired formulation was also evaluated against acetic acid-induced colitis in rats. Physical properties of the tablets were in the ranges recommended by official references. More than 10% of the drug was released in HCl 0.1 N and pH 7.4, while a very drastic increase was observed after exposure to pH 6.8 containing rat caecal contents. The efficacy of the selected formulation against rat-induced colitis was also increased in comparison to the non-targeted formulation of budesonide. In conclusion, matrix tablets with a 1:10 drug-to-dextran ratio with high molecular weight could deliver the drug specifically to the colon and are promising for treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Summary: Sentinel lymph node biopsy is rapidly becoming the standard of care in staging the axilla for early-stage, clinically node-negative breast carcinoma. This paper discusses the rationale and methods of sentinel lymph node biopsy and critically analyses the data concerning its accuracy and usefulness. The impact of axillary surgery as a staging technique and as a therapeutic intervention on breast cancer prognosis is discussed. The pathological methods for handling and assessing sentinel lymph nodes are described and evaluated. Broad guidelines on how to dissect, process, stain, assess and report sentinel lymph nodes are provided. [Copyright &y& Elsevier]

Background and aims. Most clinical practice guidelines today recommend total mesorectal excision (TME) for carcinoma of the middle and lower rectal thirds and partial mesorectal excision (PME) for the upper rectal third. However, these procedures may not always fulfill the oncological requirements. The pathological examination of resected rectal carcinomas should always include a visual assessment of the mesorectal excision to ensure oncological adequacy and appropriate quality. The clinical practice guideline of the German Cancer Society recommends reporting of the distal extent of mesorectal excision (total or partial without coning) and the excision in an inviolate fascial envelope. Patients and methods. Reporting schemas of assessment and documentation for daily use and for studies are presented. Results. Careful macroscopic evaluation of the resection specimen should be standardized. This may be supplemented by stain marking after postoperative filling the inferior mesenteric or superior rectal artery with ink or methylene blue solution. Photodocumentation is highly desirable. The pathological assessment of adequacy of mesorectal excision should be taken into account in selection for adjuvant radiotherapy. Objective macro- and microscopic assessment of mesorectal excision by pathologists is essential for quality management throughout patient care and in clinical trials. [ABSTRACT FROM AUTHOR]

Assessment of the estrous cycle of mature female mammals is an important component of verifying the efficacy and safety of drug candidates. The common pathological approach of relying on expert observation has several drawbacks, including laborious work and inter-viewer variability. The recent advent of image recognition technologies using deep learning is expected to bring substantial benefits to such pathological assessments. We herein propose 2 distinct deep learning-based workflows to classify the estrous cycle stage from tissue images of the uterine horn and vagina, respectively. These constructed models were able to classify the estrous cycle stages with accuracy comparable with that of expert pathologists. Our digital workflows allow efficient pathological assessments of the estrous cycle stage in rats and are thus expected to accelerate drug research and development., (© 2022 The Authors.)

Due to their increased detection pancreatic cystic space-occupying lesions are becoming increasingly relevant in the clinical routine and represent a morphologically and biologically heterogeneous and thus clinically demanding as well as potentially (pre)malignant entity. As a result, recommendations for the diagnostics and treatment of pancreatic cystic tumors have now been incorporated into the current German S3 guidelines on pancreatic cancer. The diagnostics of pancreatic cystic space-occupying lesions are based on the following three elements: collection of relevant clinical information, performance of high-resolution imaging procedures and if diagnostic uncertainty persists, puncture diagnostics. Differentiated diagnostics are of essential importance as these represent the basis for an adequate treatment decision. Pancreatic cystic lesions with a relevant risk of malignant transformation, e.g., main duct intraductal papillary mucinous neoplasms (IPMN), followed by mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and generally pancreatic cystic lesions with risk factors independent of the entity, should be resected, whereas a differentiated and individualized approach is necessary, especially for branch-duct IPMNs. The serous cystic neoplasms (SCN) have no malignant potential and do not require any treatment if they are asymptomatic. Important principles in surgery of pancreatic cancer, such as adequate surgical resection taking oncological standards into account and standardized appropriate histopathological processing of the specimens as well as intraoperative frozen section analysis also play an important role in pancreatic cystic space-occupying lesions. An annual follow-up seems to be meaningful, especially for IPMNs., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

High doses of the oil-soluble antimalarial artemisinin derivatives artemether and arteether, given by intramuscular injection to experimental mammals, produce an unusual pattern of selective damage to brainstem centres predominantly involved in auditory processing and vestibular reflexes. We have shown recently, in adult Swiss albino mice, that constant exposure either from depot intramuscular injection of oil-based artemisinin derivatives, or constant oral intake carries relatively greater neurotoxic potential than other methods of drug administration. Using the same model, oral dihydroartemisinin suspended in water was administered once or twice daily at different doses ranging from 50 to 300 mg/kg/day for 28 days. The neurotoxic potential of the oral dihydroartemisinin was assessed and compared to that of oral artemether and artesunate. Oral artemether, artesunate, and dihydroartemisinin had similar neurotoxic effects with no significant clinical or neuropathological evidence of toxicity at doses below 200 mg/kg/day. These data indicate that once and twice daily oral administration of artemether, artesunate and dihydroartemisinin is relatively safe when compared to intramuscular administration of the oil-based compounds. [Copyright &y& Elsevier]

Purpose: Tumor regression grade (TRG) has been widely used in gastrointestinal carcinoma to assess pathological responses to neoadjuvant chemotherapy (NCT). There are various standards without a consensus, and it is still unclear which kind of system has better predictive value. This study aims to investigate and compare the predictive ability of the Mandard and Becker TRGs in patients with locally advanced gastric cancer., Materials and Methods: A total of 290 patients with locally advanced gastric adenocarcinoma who underwent NCT and curative surgery were studied. Survival analysis for overall survival (OS) and disease-free survival (DFS) were based on the Kaplan-Meier method and Cox proportional hazards method. Predictive values of TRGs and models were assessed by time-dependent receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), nomogram, and calibration curve., Results: In multivariable analysis, the Mandard TRG was associated with OS (hazard ratio [HR], 1.806; p=0.026) and DFS (HR, 1.792; p=0.017). The Becker TRG was also related to OS (HR, 1.880; p=0.014) and DFS (HR, 1.919; p=0.006). The Mandard and Becker TRG AUCs for 5-year survival were 0.72 and 0.71, respectively. The whole models showed an increased predictive value, with AUCs of 0.85 and 0.86, respectively. There was no significant difference between the two TRGs and two models., Conclusion: TRG was an independent predictor for survival, and there was no significant difference between these two systems.

The large force applied by laparoscopic grasper during clamping operation can cause tissue damage and induce various complications. In this research, the security of graspers with different radii of curvature and teeth were evaluated by using experimental investigation, finite element simulation and tissue damage assessment method based on in vivo compression tests with rabbit large intestines models. Results showed that the most serious tissue damages appeared in areas that were in contact with the jaw edges, which were the regions of stress concentration. The increase in radii of curvature of the edges or teeth could alleviate the tissue damages. The results could provide basic data for choosing and designing noninvasive graspers.

Objective: Total mesorectal excision (TME) is the standard of care for patients with rectal cancer. Pathological evaluation of the quality of the TME specimen is an important prognostic factor that correlates with local recurrence but is potentially subjective. The objective of this study is to determine the degree of variation in grading, both between assessors and between fresh and formalinfixed specimens. Methods: The raters included surgeons, pathologists, pathologists' assistants (PAs), residents and PA students. Specimens were assessed by up to 6 raters in the fresh state and by 2 raters post fixation. The 4 parameters evaluated were: mesorectal bulk, surface regularity, presence/absence of defects and coning. Based on this assessment, the specimen was assigned an overall score. Inter-rater agreement was measured using an ordinal alpha value from a polychoric correlation matrix. Results: A total of 18 TME specimens were assessed. Interrater agreement varied across the parameters. Reliability between all raters for fresh specimens for mesorectal bulk, surface regularity, defects, coning and overall grade were 0.88, 0.90, 0.94, 0.87, and 0.93, respectively. Reliability among PAs grading fresh specimens ranged from 0.34 to 0.73 for all parameters. The agreement among PAs grading formalin fixed specimens ranged from 0.59 to 0.82 for all parameters and was better than for fresh specimens for all parameters except defects. Conclusions: The results indicate variability between assessors, with some parameters yielding better inter-rater agreement than others. This study highlights the need for additional knowledge-transfer, to ensure good consistency and accurate grading of TME specimens. [ABSTRACT FROM AUTHOR]

Background: Tissue grasping damage often occurs in minimally invasive surgery, which would increase the postoperative recovery time and the risk of surgical complications. The purpose of this study was to evaluate the relationship between liver tissue trauma and compression stress magnitude and duration during tissue clamping operation., Methods: The clamping experiments of liver tissues in vivo were conducted by using a universal soft tissue mechanical testing machine under different clamping stress magnitudes and durations. The rabbit liver was used to simulate human liver. A minimally invasive surgery grasper was used in these tests to simulate the real tissue-surgical operation condition. A pathological grading system was created to quantitatively assess the trauma within the liver tissue. The hyperbolic regression models were utilized to predict the trauma degree of liver tissue., Findings: Obvious hyperemia, hemorrhage, hepatic capsule rupture and inflammatory cell infiltration appeared in the clamping sites of the liver. Assessment results indicated that the trauma degree increased nonlinearly with the increasing clamping stress and duration time. There exist safe thresholds, in which the severe trauma of the studied tissue can be avoided during grasping operation., Interpretation: The results could provide the safety margins and the trauma prediction models for surgeons during grasping and palpation tasks in minimally invasive surgery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)