Oncological and functional outcomes of pathological fractures of lower extremities in patients with malignant bone tumors.

As managing pathological fractures of the extremities can be difficult, the present study aimed to present a treatment algorithm for lower extremity bone malignancies. A total of 38 patients with impending and pathological fractures were treated at the Department of Orthopedic Surgery in Kindai University Hospital. Age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcomes, follow-up period and the MSTS scores and ECOG-PS were compared in cases of primary malignant tumors and those cases of metastatic malignant tumors were retrospectively surveyed. Post-treatment MSTS scores in cases of impending and pathological fractures were compared between intramedullary nail fixation and non-intramedullary nail fixation procedures. Disease sites included the sub-trochanteric femur in 10 patients, trochanteric femur in 8, femoral diaphysis in 7, femoral neck in 5, bilateral trochanteric femur in 3, proximal tibia in 3 and distal femur in 2 patients. A total of 10 patients had metastases between 3-20 sites. The median pre-fracture ECOG-PS score was 1. Adjuvant radiotherapy was administered to 5, chemotherapy to 8 and radiotherapy with chemotherapy to 10 patients. Surgical procedures included intramedullary nails in 18 patients, tumor arthroplasty in 4, plate fixation in 3, artificial head replacement in three, compression hip screw (CHS) in 3, conservative treatment in 2, bilateral intramedullary nail fixation in 2 and artificial bone stem with combined intramedullary nail and plate fixation, right-sided artificial head replacement and left-sided CHS in 1 patient each. The MSTS score was 19.9±8.95 for intramedullary nail fixation and 24.3±7.45 for other procedures, with a negative association between the MSTS score and pre-fracture ECOG-PS. The median follow-up period was 8 months. The outcomes were as follows: Alive with disease, 23 patients; continued disease-free, 1 patient; and dead due to disease, 14 patients. The 1-year postoperative overall survival rate was 60.5%. Moreover, the group with metastatic malignant tumors, which had significantly worse ECOG-PS, had significantly lower MSTS scores than the group with primary malignant tumors. The authors' treatment algorithm for malignant bone tumors of the lower extremity was shown to be useful.

A sarcomatoid malignancy originating in the right cervical lymph nodes with atypical pathological characteristics: a case report of an incidental finding.

Background: Primary malignancies of the cervical lymph nodes with special pathological characteristics are relatively uncommon in clinical settings, and there have been few reports on these tumors. The precise basis for their pathogenesis is poorly understood, and their diagnosis can be challenging. In addition, no clinically validated treatments have been established to date for affected patients. Case Description: Here, we describe a case of a 65-year-old male patient who exhibited the enlargement of several lateral and supraclavicular lymph nodes on the right side of his neck that presented as a large mass associated with a high fever and benign leukocytosis. He did not exhibit any relevant prior history. Radiological assessment revealed that this lesion was the primary tumor and that it has since spread to the liver. Histological assessment was unable to definitively classify the pathological characteristics of this tumor. Without any relevant morphological findings, immunohistochemical outcomes were not sufficiently specific to clarify the origin of these cells. When distinguishing it from similar sarcomas of the lymphohematopoietic system, it was found to not be typical of a histiocytic or dendritic cell tumor. Treatment to this patient was performed following multidisciplinary consultation and consisted of one course of a cyclophosphamide plus doxorubicin, vincristine, and dexamethasone regimen and two courses of the cyclophosphamide plus pirarubicin, vincristine, and dexamethasone regimen. However, the tumor exhibited minimal response to such treatment. While radiotherapy was proposed, the patient lacked confidence in the approach and declined treatment. He eventually developed severe tumor-associated complications. In the discussion section of this report, we detail and analyze the pathogenesis, diagnosis, and referential treatments of this rare malignancy. Conclusions: This is the first report describing such a malignancy, and we hope that the publication of these findings can lead to the recognition of this tumor while supporting efforts to acquire greater experience in the diagnosis and treatment of affected patients.

Mapping Emotion Regulation Patterns Within the Alternative Model of Personality Disorders Personality Traits.

Personality pathology is associated with emotional problems that are potentially attributable to problematic emotion regulation strategy patterns. We evaluated the emotion regulation strategies associated with the pathological personality traits in the Alternative Model of Personality Disorders (AMPD). A total of 504 participants completed measures of AMPD traits and strategy usage, which were analyzed using hierarchical regressions and latent profile analysis (LPA). Regression results demonstrated that each trait was associated with a unique strategy pattern: negative affect with emotional overengagement, detachment with socialemotional avoidance, antagonism with emotional externalization/avoidance, disinhibition with emotional avoidance and overengagement, and psychoticism with strategies linked to psychotic/dissociative experiences. The LPA identified three profiles with heightened AMPD traits: an internalizing/distressed profile, an externalizing/distressed profile, and a schizoid-schizotypal profile; each had a unique strategy pattern that varied depending on trait composition. This research highlights the relevance of emotion regulation strategy patterns in the assessment, conceptualization, and treatment of personality pathology.

The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.

Rectal adenocarcinoma: Ex vivo 9.4T MRI-correlation with histopathologic treatment response to neoadjuvant chemoradiotherapy.

OBJECTIVES: To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo. METHODS: Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether-filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI-based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings. RESULTS: The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images. CONCLUSION: Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.

Association between homologous recombination deficiency status and carboplatin treatment response in early triple-negative breast cancer.

BACKGROUND: The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients. METHODS: Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients. RESULTS: HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment. CONCLUSION: TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.

Characteristics and clinical significance of tertiary lymphoid structures in OSCC.

OBJECTIVES: This study aimed to investigate the characteristics of tertiary lymphoid structures (TLSs) in oral squamous cell carcinoma (OSCC) and their association with clinical and pathological features. MATERIALS AND METHODS: 12 TLS-related chemokines in TCGA database were analyzed to investigate the TLSs in OSCC. The density, maturity, and location of TLSs in a large cohort of 189 OSCC patients (114 of which had clinical and prognostic information) were assessed. And the significance between TLSs and clinicopathologic characteristics was analyzed. RESULTS: Bioinformatics and analysis showed that TLSs were associated with better clinical outcomes in OSCC. Histological staining and analysis showed that the overall survival rate of the high-density group (71/112, 63.4%) was significantly higher (p < 0.0001) than that of the low-density group (41/112, 36.6%), and the high-density group had fewer lymph node metastases (50.0%/68.3%, p = 0.021). And TLSs were divided into 4 types according to the maturity and location. Different types of TLSs are associated with prognosis (OS, p < 0.0001), clinical features (T stage, p = 0.028; degree of differentiation, p = 0.043), and precancerous lesion types (OSF, p = 0.049) of OSCC patients. CONCLUSION: TLSs were closely associated with better OSCC prognosis, and a more systematic classification may better guide the formulation of further treatment options.

Ultrasound and diffuse optical tomography-transformer model for assessing pathological complete response to neoadjuvant chemotherapy in breast cancer.

Significance: We evaluate the efficiency of integrating ultrasound (US) and diffuse optical tomography (DOT) images for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. The ultrasound-diffuse optical tomography (USDOT)-Transformer model represents a significant step toward accurate prediction of pCR, which is critical for personalized treatment planning. Aim: We aim to develop and assess the performance of the USDOT-Transformer model, which combines US and DOT images with tumor receptor biomarkers to predict the pCR of breast cancer patients under NAC. Approach: We developed the USDOT-Transformer model using a dual-input transformer to process co-registered US and DOT images along with tumor receptor biomarkers. Our dataset comprised imaging data from 60 patients at multiple time points during their chemotherapy treatment. We used fivefold cross-validation to assess the model's performance, comparing its results against a single modality of US or DOT. Results: The USDOT-Transformer model demonstrated excellent predictive performance, with a mean area under the receiving characteristic curve of 0.96 (95%CI: 0.93 to 0.99) across the fivefold cross-validation. The integration of US and DOT images significantly enhanced the model's ability to predict pCR, outperforming models that relied on a single imaging modality (0.87 for US and 0.82 for DOT). This performance indicates the potential of advanced deep learning techniques and multimodal imaging data for improving the accuracy (ACC) of pCR prediction. Conclusion: The USDOT-Transformer model offers a promising non-invasive approach for predicting pCR to NAC in breast cancer patients. By leveraging the structural and functional information from US and DOT images, the model offers a faster and more reliable tool for personalized treatment planning. Future work will focus on expanding the dataset and refining the model to further improve its accuracy and generalizability.

Liposomes Loaded with 5-Fluorouracil Can Improve the Efficacy in Pathological Scars.

Introduction: Pathological scars, such as hypertrophic scars and keloids, are characterized by the proliferation of fibroblasts and the deposition of collagen that often cause pruritus, pain, and disfigurement. Due to their high incidence and deformity, pathological scars have resulted in severe physical and psychological trauma for patients. Intralesional injection of 5-fluorouracil (5-Fu) is a recommended option for treating pathological scars. However, the efficacy of 5-Fu injection was limited and unstable due to limited drug penetration and short retention time. Methods: Liposomes are promising carriers that have advantages, such as high biocompatibility, controlled release property, and enhanced clinical efficacy. Here, we constructed a transdermal 5-Fu-loaded liposome (5-Fu-Lip) to provide a more effective and safer modality to scar treatment. Results: Compared to 5-Fu, 5-Fu-Lip showed superior ability in inhibiting primary keloid fibroblasts proliferation, migration, and collagen deposition, and also significantly inhibited human umbilical vein endothelial cells (HUVECs) proliferation and microvessel construction. In vivo experiments demonstrated that 5-Fu-Lip can significantly reduce the severity of hypertrophic scars in a rabbit ear wounding model. Discussion: 5-Fu-Lip provides a promising strategy to improve drug efficacy, which has great potential in the treatment of pathological scars.

TP53 signature predicts pathological complete response after neoadjuvant chemotherapy for breast cancer: Observational and confirmational study using prospective study cohorts.

The TP53 signature is considered a predictor of neoadjuvant chemotherapy (NAC) response and prognostic factor in breast cancer. The objective of this study was to confirm TP53 signature can predict pathological complete response (pCR) and prognosis in cohorts of breast cancer patients who received NAC in prospective studies. Development cohorts (retrospective [n = 37] and prospective [n = 216] cohorts) and validation cohorts (NAC administered prospective study cohorts [n = 407] and retrospective perioperative chemotherapy (PC)-naïve, hormone receptor (HrR)-positive cohort [PC-naïve_HrR+ cohort] [n = 322]) were used. TP53 signature diagnosis kit was developed using the development cohorts. TP53 signature predictability for pCR and the relationship between recurrence-free survival (RFS), overall survival (OS), and the TP53 signature were analyzed. The pCR rate of the mutant (mt) signature group was significantly higher than that of the wild-type (wt) signature group (odds ratio, 5.599; 95 % confidence interval = 1.876-16.705; P = 0.0008). The comparison of the RFS and OS between the HrR+ and HER2- subgroup of the NAC cohort and of the PC-naïve_HrR+ cohort indicated that the RFS and OS benefit of NAC was greater in the mt signature group than in the wt signature group. From post hoc analyses, the RFS and OS benefit from adding capecitabine to FEC+T as NAC might be observed only in the mt signature group. The TP53 signature can predict the pCR after NAC, and the RFS and OS benefit from NAC may be greater in the mt signature group than in the wt signature group.

Predictive values of cervix length measurement based on transvaginal ultrasonography.

BACKGROUND: Pregnancy is an important process in women's life, which is widely concerned by women. In recent years, the incidence of premature delivery (PTD) becomes more and more higher due to the development of auxiliary reproduction and ovulation induction technologies and the changes of pregnant women's lifestyle and physical quality. PTD not only affects postpartum recovery and causes great physical pains, but it also has adverse effects on the birth state of neonates and even leads to neonatal death. OBJECTIVE: The predictive values of cervix length (CL) measurement based on transvaginal ultrasonography (TVUS) and pathological examination of placenta for premature delivery (PTD) were investigated and the correlation between PTD and infection was analyzed. METHODS: 120 pregnant women with PTD or high-risk factors for PTD admitted to The Affiliated Hospital of Southwest Medical University between February 2020 and March 2022 were included as the subjects and underwent pathological examination of placenta and TVUS for CL measurement. The final gestational age was set as the standard for the evaluation on the predictive values of pathological examination of placenta and TVUS. What's more, 36 subjects in PTD group and 84 in normal delivery group (control group) underwent pathological examination of placenta for the analysis of the correlation between PTD and infection. RESULTS: The joint inspection method showed significantly better sensitivity, specificity, PPV, and NPV compared to single CL or pathological examination of the placenta (P< 0.05). Among pregnant women, those with CL ⩽ 30 mm and positive placental pathology had a higher proportion compared to those with CL > 30 mm and negative placental pathology (P< 0.05). Furthermore, the incidence of Ureaplasma Urealyticum (UU), Chlamydia Trachomatis (CT), and Chorioamnionitis (CA) in vaginal discharge of the preterm delivery (PTD) group was significantly higher than that of the control group (P< 0.05). CONCLUSION: The combination of CL ⩽ 30 mm and positive placental pathology could effectively predict PTD and placental infection was notably correlated with the occurrence of PTD.

Surgical outcomes of proximal femoral bone cysts in pediatric patients: a retrospective study of 41 cases.

Purpose: The aim of this study was to evaluate the surgical outcomes of proximal femoral bone cysts in pediatric patients. Methods: We retrospectively analyzed 41 pediatric patients (31 males and 10 females, mean age 7.47 ± 2.67 years, range 2.03-14.67 years) diagnosed with proximal femoral bone cysts treated at a single institute between March 2009 and November 2021. Data included demographics, preoperative details, intraoperative conditions, surgical techniques, postoperative outcomes, recurrence, and complications. Results: Of the participants, 68% presented with simple bone cysts and 32% with aneurysmal bone cysts. Prior to surgery, 32% exhibited pathological fractures. Surgical methods included lesion curettage, defect filling using allograft bone and Minimally-Invasive Injectable Graft ×3, and varied fixation techniques. Postoperative recurrence (17%) was associated with cyst location between the capital femoral epiphysis and the linea intertrochanterica (P = 0.010). At the final assessment (mean follow-up: 26.51 ± 18.99 months), all showed radiological bony union with 93% rated as "good" and 7% as 'fair' based on Ratliff hip scores. Complications arose in 20% of patients, significantly correlated with prior pathological fractures (P = 0.007) and their association with the linea intertrochanterica (P = 0.004). Those with fractures reported higher intraoperative blood loss (P = 0.015) and longer surgery durations (P = 0.012) compared to those without. Conclusion: Treating pediatric proximal femoral bone cysts using techniques such as lesion curettage, defect filling, and selective internal fixation yields favorable outcomes. The presence of pathological fractures can prolong surgical time, increase intraoperative blood loss, and elevate postoperative complication risks. Hence, early surgical intervention for these cysts is recommended to prevent fractures.

Carnosol suppresses cardiomyocyte hypertrophy via promoting the activation of AMPK pathway.

Pathological cardiac hypertrophy is associated with adverse cardiovascular events and can gradually lead to heart failure, arrhythmia, and even sudden death. However, the current development of treatment strategies has been unsatisfactory. Therefore, it is of great significance to find new and effective drugs for the treatment of myocardial hypertrophy. We found that carnosol can inhibit myocardial hypertrophy induced by PE stimulation, and the effect is very significant at 5 µM. Moreover, we demonstrated that 50 mg/kg of carnosol protect against cardiac hypertrophy and fibrosis induced by TAC surgery in mice. Mechanically, we proved that the inhibitory effect of carnosol on cardiac hypertrophy depends on its regulation on the phosphorylation activation of AMPK. In conclusion, our study suggested that carnosol may be a novel drug component for the treatment of pathological cardiac hypertrophy.

Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report.

BACKGROUND: No reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies. CASE PRESENTATION: A 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening. CONCLUSIONS: This is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.

Successful treatment of enormous locally advanced breast cancer through neoadjuvant chemotherapy and surgical intervention: a case report.

Background: Breast cancer has become a critical international healthcare issue. Specifically, among the different subtypes, breast cancer marked by human epidermal growth factor receptor 2 (HER2)-overexpression usually correlates with low survival and a poor prognosis and poses challenges in treatment, thus leading to high mortality. Case Description: A 54-year-old female patient was diagnosed with a large T4cN2aM0 stage IIIB breast tumor with HER2 overexpression. The tumor size was large, and there was a lack of opportunity for surgery. However, after neoadjuvant chemotherapy (NACT), the size of the tumor continuously shrank, and the patient successfully underwent a modified radical mastectomy. Even though a certain amount of mass remained and she did not complete six courses of NACT, our patient's postoperative pathological result still revealed that a pathological complete response (pCR) was achieved. The appropriate time window for choosing surgical intervention should be determined based on the patient's general condition instead of complying with the treatment guidelines. Also, imaging findings may be misleading in patients who have undergone NACT. Moreover, the regimen should be chosen flexibly. Conclusions: Patients with locally advanced breast cancer can still achieve a radical surgical resection following appropriate comprehensive treatment. Hopefully, this case can provide new ideas for surgeons when they face similar conditions.

Causal relationship between gut microbiota and pathological scars: a two-sample Mendelian randomization study.

Background: Pathological scars, including keloids and hypertrophic scars, represent a significant dermatological challenge, and emerging evidence suggests a potential role for the gut microbiota in this process. Methods: Utilizing a two-sample Mendelian randomization (MR) methodology, this study meticulously analyzed data from genome-wide association studies (GWASs) relevant to the gut microbiota, keloids, and hypertrophic scars. The integrity and reliability of the results were rigorously evaluated through sensitivity, heterogeneity, pleiotropy, and directionality analyses. Results: By employing inverse variance weighted (IVW) method, our findings revealed a causal influence of five bacterial taxa on keloid formation: class Melainabacteria, class Negativicutes, order Selenomonadales, family XIII, and genus Coprococcus2. Seven gut microbiota have been identified as having causal relationships with hypertrophic scars: class Alphaproteobacteria, family Clostridiaceae1, family Desulfovibrionaceae, genus Eubacterium coprostanoligenes group, genus Eubacterium fissicatena group, genus Erysipelotrichaceae UCG003 and genus Subdoligranulum. Additional sensitivity analyses further validated the robustness of the associations above. Conclusion: Overall, our MR analysis supports the hypothesis that gut microbiota is causally linked to pathological scar formation, providing pivotal insights for future mechanistic and clinical research in this domain.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment: A Case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of patients with Epidermal growth factor receptor (EGFR) sensitive mutations in non-small cell lung cancer (NSCLC). CASE SUMMARY: A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment. Secondary pathological tissue biopsy confirmed squamous cell carcinoma (SCC) transformation. Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time, while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC. Notably, EGFR-TKIs resistance includes primary and acquired. Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs, with SCC transformation being relatively rare. Our results provide more detailed results of the patient's diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma. CONCLUSION: Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

Pathological Changes Following Neoadjuvant Endocrine Therapy (NAET): A Multicentre Study of 391 Breast Cancers.

Oestrogen receptor (ER)-positive breast cancer (BC) is generally well responsive to endocrine therapy. Neoadjuvant endocrine therapy (NAET) is increasingly being used for downstaging ER-positive tumours. This study aims to analyse the effect of NAET on a well-characterised cohort of ER-positive BC with particular emphasis on receptor expression. This is a retrospective United Kingdom (UK) multicentre study of 391 patients who received NAET between October 2012 and October 2020. Detailed analyses of the paired pre- and post-NAET morphological changes and hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression were performed. The median duration of NAET was 86 days, with median survival and overall survival rates of 380 days and 93.4%, respectively. A total of 90.3% of cases achieved a pathological partial response, with a significantly higher rate of response in the HER2-low cancers. Following NAET, BC displayed some pathological changes involving the tumour stroma including central scarring and an increase in tumour infiltrating lymphocytes (TILs) and tumour cell morphology. Significant changes associated with the duration of NAET were observed in tumour grade (30.6% of cases), with downgrading identified in 19.3% of tumours (p < 0.001). The conversion of ER status from positive to low or negative was insignificant. The conversion of progesterone receptor (PR) and HER2 status to negative status was observed in 31.3% and 38.1% of cases, respectively (p < 0.001). HER2-low breast cancer decreased from 63% to 37% following NAET in the paired samples. Significant morphological and biomarker changes involving PR and HER2 expression occurred following NAET. The findings support biomarker testing on pre-treatment core biopsies and post-treatment residual carcinoma.

Deep Residual Learning-Based Classification with Identification of Incorrect Predictions and Quantification of Cellularity and Nuclear Morphological Features in Digital Pathological Images of Common Astrocytic Tumors.

Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.