Pathological Subtypes Research Articles

Post-marketing surveillance data for avelumab + axitinib treatment in patients with advanced renal cell carcinoma in Japan: Subgroup analyses by pathological classification.

Clinical trials have demonstrated the efficacy and safety of avelumab + axitinib in patients with advanced clear cell renal cell carcinoma (ccRCC). However, information is limited regarding the activity of avelumab + axitinib in patients with non-clear cell RCC (nccRCC). In Japan, post-marketing surveillance (PMS) of patients with RCC receiving avelumab + axitinib treatment in general clinical practice was undertaken. We report ad hoc analyses of PMS data according to RCC pathological classification. Of 328 patients with RCC who received ≥1 dose of avelumab and were enrolled between December 2019 and May 2021, 271 (82.6%) had ccRCC, 22 (6.7%) had nccRCC, and 35 (10.7%) had missing or unknown RCC pathology. Among patients with nccRCC, pathological subtypes were papillary in 12 (3.7%), translocation in 3 (0.9%), acquired cystic disease associated in 3 (0.9%), chromophobe in 2 (0.6%), mucinous tubular and spindle cell in 1 (0.3%), and Bellini duct in 1 (0.3%). Among patients with ccRCC or nccRCC, any-grade adverse drug reactions of safety specifications occurred in 140 (51.7%) and 15 (68.2%), and of grade ≥3 in 48 (17.7%) and 6 (27.3%), respectively. The objective response rate in patients with ccRCC or nccRCC was 36.9% and 22.7%, respectively; in patients with papillary tumors, it was 33.3%. Median overall survival was not reached in patients with ccRCC or nccRCC, and 12-month overall survival rates were 86.8% and 76.7%, respectively. Overall, subgroup analyses of PMS data suggest that avelumab + axitinib improved clinical outcomes in nccRCC in addition to ccRCC.

Longitudinal Testing of Circulating Tumor DNA in Patients With Metastatic Renal Cell Carcinoma.

Tumor-informed circulating tumor DNA (ctDNA) has shown promise as a biomarker for treatment response monitoring (TRM) in a variety of tumor types, with the potential to improve clinical outcomes. We evaluated ctDNA status and dynamics during surveillance and as part of TRM with clinical outcomes in both patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC) treated with standard-of-care immunotherapy or targeted therapy regimens. This was a multicenter retrospective analysis of real-world data obtained from commercial ctDNA testing (Signatera, Natera, Inc) in patients with metastatic RCC. Clinical data were collected on International Metastatic RCC Database Consortium (IMDC) risk category, pathologic subtype, and grade. The cohort comprised 92 patients (490 plasma samples) including both clear cell and non-clear cell histological subtypes (ccRCC: 79.3%; nccRCC: 14.1%; unclassified: 6.5%). Most of the patients belonged to the IMDC intermediate-risk category (75%, 69/92). Median follow-up was 10 months (range, 4.2-25.8). ctDNA dynamics were assessed in 56 patients on treatment, and ctDNA status was analyzed in the surveillance cohort (n = 32 patients). Serial ctDNA negativity or clearance correlated with improved progression-free survival (PFS) compared with those who became or were persistently ctDNA positive on therapy (hazard ratio [HR], 3.2; P = .012). In the surveillance cohort, patients with positive ctDNA longitudinally experienced significantly inferior PFS (HR, 18; P = .00026) compared with those who were serially negative. Collectively, we show that serial ctDNA monitoring provides prognostic information for patients undergoing treatment or surveillance, and our findings demonstrate high concordance between ctDNA status/dynamics and subsequent clinical outcomes.

CT-based radiomics analysis for prediction of pathological subtypes of lung adenocarcinoma

ObjectiveLung cancer is a leading cause of cancer-related deaths worldwide, and its early and accurate diagnosis is crucial for improving patient survival. This paper developed an artificial intelligence (AI) model based on machine learning combined with radiomics for predicting the pathologic type of ground glass nodules (GGN). It explored its potential and challenges in practical applications. MethodsA total of 179 GGN patients with postoperative pathologically confirmed lung adenocarcinoma from June 2022 to June 2024 were collected from a hospital, including 22 cases of atypical adenomatous hyperplasia (AAH), 61 cases of adenocarcinoma in situ (AIS), 55 cases of invasive adenocarcinoma (IAC), and 41 cases of minimally invasive adenocarcinoma (MIA). Two experienced radiologists outlined the imaging data's regions of interest (ROI). Radiomic features were extracted and selected through normalization, mutual information, Spearman correlation coefficient, recursive feature elimination, and LASSO regression. Different machine learning models were developed and the best model was determined based on classification accuracy. ResultsDifferent machine learning models were trained and tested, and a variety of deep learning models were selected for comparison, among which Random Forest had the highest accuracy of 83.3%, and the AUC value of 0.892(95%CI, 0.846-0.923) in recognizing lung adenocarcinoma types. The AUC values reached 0.92 and 0.94 respectively in diagnosing AIS and IAC. ConclusionRadiomics combined with machine learning models, such as Random Forest, outperform average physician diagnostic accuracy in identifying lung adenocarcinoma types. The model is valuable for early and precise lung adenocarcinoma diagnosis, enhancing clinical decision-making.

Endoscopic Endonasal Approach for Calcified Sellar/Parasellar Region Pathologies: Report of 11 Pituitary Adenoma Cases

Calcification in pituitary adenomas is a rare occurence and its differential diagnosis typically includes other sellar masses.Common calcifications in pituitary adenomas are classified into two morphological forms: capsular(eggshell-like)and multiple small nodular calcifications located within the adenoma.Also,there is a pituitary stone term.This study aims to present the results of calcified pituitary adenoma case series who underwent endoscopic endonasal approach(EEA)and the clinical,histopathological characteristics and surgical outcomes of these cases. This study conducted a retrospective cohort analysis of patients with calcified pituitary adenoma operated on by EEA between August 1997 and February 2024.The inclusion criteria were as follows:proven radiological calcification on pre-operative neuroimaging,intraoperative findings of calcification and definitive histopathological diagnosis of calcification.Among these patients,11 cases were included. The mean follow-up duration was 51.45±37.24 (6-118)months.Based on the pre-operative paranasal sinus computed tomography(CT)scans of patients,nine patients(81.8%)had intratumoral calcification,one(9.1%)had capsular(eggshell like)calcification and one(9.1%)had both intratumoral and capsular calcification.Moreover,stone-like calcifications were observed in four patients(36.4%),soft type calcifications in three(27.3%),hard-type calcifications in three(27.3%)and soft and hard-type calcifications in one(9%).Gross total resection(GTR)was achieved in nine patients(81.8%).Pathologic subtypes included non-functioning(n = 4),prolactin secreting(n = 3),growth hormone secreting adenoma(n = 2)and pituitary apoplexy(n = 2).Ten patients had psammomatous type calcifications and one had extensive ossification and osteoid metaplasia. Pre-operative radiological evaluation,intraoperative classification of calcification,and post-operative histopathological assessments are crucial in the treatment of calcified adenomas.Bases on these findings,the EEA,with its advantages,is an approach that can be effectively used in the management of these calcified adenomas.

A case report of an individual with Creutzfeldt–Jakob disease characterized by prolonged isolated thalamic lesions and rare MM2-cortical-type pathology

BackgroundDiffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing Creutzfeldt–Jakob disease (CJD). Thalamic lesions are rarely detected by DWI in sporadic CJD (sCJD) cases with methionine homozygosity at polymorphic codon 129 (129MM) of the prion protein (PrP) gene. Here, we describe an unusual sCJD case, characterized by prolonged isolated thalamic diffusion hyperintensities and atypical brain pathology, in combination with the 129MM genotype.Case presentationA 72-year-old Japanese man developed a mild unsteady gait that had persisted for 1 year. DWI revealed isolated thalamic diffusion hyperintensities. Over the following 4 years, his condition progressed to include ataxia and cognitive decline. Repeated cerebrospinal fluid tests were negative for 14-3-3 protein, total tau protein, and real-time quaking-induced conversion assay. Electroencephalography did not show periodic sharp wave complexes or generalized periodic discharges. Despite these findings, thalamic DWI abnormalities persisted and evolved to include cortical lesions in the later stage of the disease. Genetic testing confirmed a 129MM genotype with no pathogenic PrP gene variants. Brain autopsy identified type 2 pathogenic PrP and the absence of the M2-thalamic prion strain, suggesting an MM2-cortical (MM2C)-subtype of sCJD. Histopathology revealed small vacuoles (sv) and patchy-perivacuolar PrP deposits without large vacuoles (lv). Patchy-perivacuolar deposits are a characteristic feature of the MM2C (lv) subtype and indicate MM2C (lv) pathology. Thus, this case was classified as a rare MM2C (sv + lv) subtype. No PrP protein staining was observed in the thalamus, despite spongiform changes with small vacuoles.ConclusionsThis case underscores the diagnostic challenges of atypical CJD with isolated thalamic abnormalities on DWI. Despite negative cerebrospinal fluid findings and clinical diagnostic criteria, persistent DWI abnormalities and evolving clinical symptoms continued to raise suspicion of CJD. A definitive diagnosis, being the MM2C (sv + lv) subtype of sCJD, was confirmed upon pathological examination. Even when atypical findings, such as isolated thalamic abnormalities, are observed and various tests are negative, if suspicion of CJD cannot be ruled out, it is important to confirm the diagnosis and pathological subtypes via postmortem analysis.

Comparison of 18F-FDG and 68Ga-DOTATATE PET/CT in surgically treated lung carcinoid tumors

Aims: This study aims to compare the efficacy of FDG-18 PET/CT and 68Ga-DOTATATE PET/CT imaging techniques in patients with lung carcinoid tumors, identifying the most appropriate preoperative nuclear medicine technique for diagnosis and staging. Methods: We retrospectively analyzed data from 123 patients who underwent surgery for lung carcinoid tumors at our center between 2009 and 2021. All of the patients were scanned with FDG-18 PET/CT before surgery. In addition to FDG-18 PET/CT, 68Ga-DOTATATE PET/CT scanning was performed in 28 patients: 17 in the preoperative and 11 in the postoperative period. Demographic data, mean higher maximal standard uptake (SUVmax) values of primary mass, lymph nodes and extrathoracic foci, pathologic subtype, and type of surgery were recorded. Compliance with normal distribution for numerical data was assessed using the Shapiro-Wilk test. The Wilcoxon signed-rank test was employed for groups meeting normal distribution to compare continuous numerical variables. The Mann-Whitney U and Kruskal-Wallis tests were used when normal distribution assumptions were unsatisfied. Results: The mean SUVmax value in 68Ga-DOTATATE PET/CT was significantly higher than FDG-18 PET/CT in patients with a lung carcinoid tumor (20 vs 4.4). For 68Ga-DOTATATE PET/CT scan, typical carcinoids had higher mean SUVmax value than atypical carcinoids (26 and 5.6 respectively), and the difference was statistically significant (p=0.002). For that FDG18 PET/CT, on the contrary, the mean SUVmax value was higher in atypical carcinoids than typical carcinoids (5.4 and 3.8, respectively), and the difference was not significant (p=0.126) Conclusion: The SUVmax values from 68Ga-DOTATATE PET/CT and FDG-18 PET/CT in lung carcinoid tumors vary by tumor subtype. 68Ga-DOTATATE PET/CT demonstrates higher SUVmax values in typical carcinoid tumors, indicating its superiority over FDG-18 PET/CT for this subtype. Although 68Ga-DOTATATE PET/CT also shows elevated SUVmax in atypical carcinoid tumors, the difference compared to FDG-18 PET/CT does not reach statistical significance.

Effect of POD24 on the prognosis of follicular and other indolent B-cell non-hodgkin lymphomas.

Indolent B-cell non-Hodgkin lymphomas(B-NHL) encompass a heterogeneous category of lymphomas characterized by a wide range of pathological subtypes. With the application of chemoimmunotherapy with rituximab (R-chemo), the prognosis of patients has improved considerably, with a 10-year survival rate of 60-80%. Despite these advancements, a significant number of patients still experience disease progression during or shortly after initial treatment. Those who progress within the first 24 months (POD24) continue to face a notably worse prognosis. This study aims to explore the significance of POD24 in predicting the prognosis of different subtypes of indolent B-cell NHL through a comprehensive literature review. The investigation extends to examining the existing prognostic assessment tools and evaluating the interrelationship between POD24 and these tools. By synthesizing relevant research findings, this study seeks to contribute to the current understanding of the role POD24 plays in prognostic evaluation and its potential implications in guiding clinical decision-making for patients with indolent B-cell NHL.

GPD1L may inhibit the development of esophageal squamous cell carcinoma through the PI3K/AKT signaling pathway: bioinformatics analysis and experimental exploration.

Esophageal squamous carcinoma (ESCC) is the most prevalent pathological subtype of esophageal cancer (EC). It has the characteristics of significant local invasion, quick disease progression, high recurrence rates, and a dismal prognosis for survival. Phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) is a signaling system whose aberrant activation regulates downstream factors, leading to the promotion of cancer development. This study looks at a protein called Glycerol-3-phosphate dehydrogenase 1-like (GPD1L), which strongly affects the development of several cancers. However, its association with ESCC development and its underlying mechanisms are not clear. In this paper, we analyzed six ESCC transcriptome data obtained from the GEO database. We utilized bioinformatics technology and immunohistochemistry to differentially analyze GPD1L levels of mRNA and protein expression in ESCC and normal adjacent tissues. Furthermore, we conducted survival, co-expression, enrichment, immune infiltration and drug sensitivity analysis. Moreover, we further investigated the role and mechanism of GPD1L by Western Blot (WB), Cell Counting Kit-8 (CCK8), wound healing assay, Transwell assay, and flow cytometry. Finally, the addition of IGF-1, the activator of PI3K/AKT, could rescue the inhibitory effect of GPD1L on ESCC. The findings manifest that the expression of GPD1L was low in ESCC, and functional experiments showed that GPD1L promoted apoptosis in vitro while blocking cell migration, invasion, and proliferation. Based on mechanism research, GPD1L's impact on ESCC could be explained by its suppression of the PI3K/AKT signaling pathway's activation. To sum up, our findings imply that GPD1L may impede the initiation and advancement of ESCC via modulating the PI3K/AKT signaling pathway. GPD1L is considered to be a promising therapeutic target and biomarker to diagnose and treat ESCC.

Clinicopathological features of epithelioid hemangioma of 43 patients with long-term follow-up: A two-center retrospective study.

Epithelioid hemangioma (EH) is a rare angioproliferative disorder for which histopathology is the main approach to diagnosis. The tendency to recur is of concern to clinicians and patients. The factors associated with recurrence have been sporadically reported and a large-scale cohort study has been lacking. This study aims to investigate the clinicopathological characteristics and long-term clinical outcomes of EH patients from two tertiary care hospitals. A two-center retrospective cohort study of 43 patients with a diagnosis of EH between 2013 and 2023 was evaluated at follow-up. A comprehensive and detailed review of clinical and pathological data with long-term follow-up was performed. Information on prognosis was available for 43, and 8 (8/43, 18.6%) experienced local recurrence. Facial (Cramer's V = 0.405, P = 0.029) and multiple (relative risk [RR] 4.306, 95% confidence interval [CI] 1.213, 15.282, Phi = 0.369, P = 0.016) lesions, subcutaneous involvement (RR 5.063, 95% CI 1.157, 22.151, Phi = 0.374, P = 0.014), and the presence of lymphoid follicles (RR 9.750, 95% CI 3.853, 24.671, Phi = 0.670, P < 0.001) were associated with higher recurrence rates. According to the presence or absence of well-differentiated angiogenesis, EH can be pathologically classified into vascular, cellular, and intermediate types, while the depth, degree, and pattern of inflammation, tissue eosinophilia, eosinophilic microabscesses, and hobnail endothelial cells differed significantly between cellular and vascular types. The characteristics of EH are distinguished by different pathological subtypes. This study provides insight into the clinicopathological features and outcome of EH to assist clinicians in the diagnosis and management of this rare condition.

Survival outcomes of lymph node dissection in early-stage epithelial ovarian cancer: identifying suitable candidates

ObjectiveThe study aimed to assess the effect of lymph node dissection on survival outcomes in patients presenting with early-stage epithelial ovarian cancer and to delineate patient characteristics that may indicate a greater benefit from pelvic lymph node dissection.MethodsA retrospective analysis was performed on individuals diagnosed with clinical stage I-II epithelial ovarian cancer who received primary cytoreductive surgery at the Cancer Hospital Affiliated with Harbin Medical University from January 1, 2010, to January 1, 2018. The investigation encompassed an examination of demographic data, clinicopathological profiles, perioperative complications, and survival outcomes.ResultsA total of 315 patients diagnosed with ovarian cancer were incorporated into the study and were segregated into two distinct cohorts: 217 patients who underwent lymphadenectomy (Group A) and 98 patients who did not undergo the procedure (Group B). The disparities in progression-free survival and overall survival between the two cohorts did not attain statistical significance (p > 0.05). Upon conducting a subgroup analysis, it was discerned that patients characterized by clear cell carcinoma as the pathological subtype demonstrated a significantly extended progression-free survival post-lymphadenectomy (p = 0.02). Additionally, the operative duration for the patients in Group A was significantly protracted in comparison to Group B (146.15 ± 39.132 min vs. 133.49 ± 35.308 min, P = 0.043).ConclusionFor patients with early-stage ovarian cancer, lymph node dissection does not significantly improve progression-free or overall survival rates. Our findings suggest that individuals with clear cell carcinoma pathology have a higher probability of benefiting in terms of survival following lymph node dissection.

The Correlation Between the Natural Course, Pathologic Properties With Ki-67 Expression in Lung Adenocarcinoma Presenting as Ground-Glass Nodules.

With the increasing use of lung cancer screening, the detection of ground glass nodules (GGNs) has risen. However, the natural course of GGNs and their relationship to pathologic features remains unclear. Differentiating between invasive and pre-invasive lesions based on GGN growth may improve clinical intervention timing. Ki-67, a proliferation marker, holds value in assessing tumor malignancy. This study analyzes the association between GGN growth, pathology, and Ki-67 expression to provide new insights into early-stage lung cancer management. We retrospectively evaluated 183 GGNs with at least two preoperative CT scans. Nodule location, type, natural course, and volume doubling time (VDT) were compared between invasive adenocarcinoma (IAC) and pre-IAC groups. We also assessed differences in Ki-67 expression and correlated VDT with Ki-67 levels. A total of 183 nodules were finally included; gender, nodule location, smoking history, and duration of follow-up did not differ between the IAC group and the pre-IAC group, whereas age was statistically different between the two groups. Of the 183 nodules, 52 showed growth and the predominant pathologic type was IAC, these IACs showed more PSN in nodule type, while the IAC group showed more significant differences in nodule type, nodules growth, and VDT than the pre-IAC group. There were also differences in pathologic type and VDT between different Ki-67 expression groups, and Ki-67 expression gradually increased as VDT decreased. Lung adenocarcinoma (LUAD) presenting as GGNs exhibit distinct natural courses among pathologic subtypes. VDT effectively distinguishes these growth characteristics, with IACs showing shorter VDT. The significant correlation between VDT and Ki-67 expression suggests that combining these parameters may provide valuable insights into the biological behavior and invasiveness of LUAD.

Predictive value of metabolic parameters and apparent diffusion coefficient derived from 18F-FDG PET/MR in patients with non-small cell lung cancer

BackgroundMultiple models intravoxel incoherent motion (IVIM) based 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance(18F-FDG PET/MR) could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non-small cell lung cancer (NSCLC) still needs to be further explored.ObjectiveTo compare the value of 18F-FDG PET/MR metabolic parameters and diffusion parameters in the prognostic assessment of patients with NSCLC.Meterial and methodsChest PET and IVIM scans were performed on 61 NSCLC patients using PET/MR. The maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), diffusion coefficient (D), perfusion fraction (f), pseudo diffusion coefficient (D*) and apparent diffusion coefficient (ADC) were calculated. The impact of SUVmax, MTV, TLG, D, f, D*and ADC on survival was measured in terms of the hazard ratio (HR) effect size. Overall survival time (OS) and progression-free survival time (PFS) were evaluated with the Kaplan–Meier and Cox proportional hazard models. Log-rank test was used to analyze the differences in parameters between groups.Results61 NSCLC patients had an overall median OS of 18 months (14.75, 22.85) and a median PFS of 17 months (12.00, 21.75). Univariate analysis showed that pathological subtype, TNM stage, surgery, SUVmax, MTV, TLG, D, D* and ADC were both influential factors for OS and PFS in NSCLC patients. Multifactorial analysis showed that MTV, D* and ADC were independent predicting factors for OS and PFS in NSCLC patients.ConclusionMTV, D* and ADC are independent predicting factors affecting OS and PFS in NSCLC patients. 18F-FDG PET/MR-derived metabolic parameters and diffusion parameters have clinical value for prognostic assessment of NSCLC patients.

Differentiation of pathological subtypes and Ki-67 and TTF-1 expression by dual-energy CT (DECT) volumetric quantitative analysis in non-small cell lung cancer

BackgroundTo explore the value of dual-energy computed tomography (DECT) in differentiating pathological subtypes and the expression of immunohistochemical markers Ki-67 and thyroid transcription factor 1 (TTF-1) in patients with non-small cell lung cancer (NSCLC).MethodsBetween July 2022 and May 2024, patients suspected of lung cancer who underwent two-phase contrast-enhanced DECT were prospectively recruited. Whole-tumor volumetric and conventional spectral analysis were utilized to measure DECT parameters in the arterial and venous phase. The DECT parameters model, clinical-CT radiological features model, and combined prediction model were developed to discriminate pathological subtypes and predict Ki-67 or TTF-1 expression. Multivariate logistic regression analysis was used to identify independent predictors. The diagnostic efficacy was assessed by the area under the receiver operating characteristic curve (AUC) and compared using DeLong’s test.ResultsThis study included 119 patients (92 males and 27 females; mean age, 63.0 ± 9.4 years) who was diagnosed with NSCLC. When applying the DECT parameters model to differentiate between adenocarcinoma and squamous cell carcinoma, ROC curve analysis indicated superior diagnostic performance for conventional spectral analysis over volumetric spectral analysis (AUC, 0.801 vs. 0.709). Volumetric spectral analysis exhibited higher diagnostic efficacy in predicting immunohistochemical markers compared to conventional spectral analysis (both P < 0.05). For Ki-67 and TTF-1 expression, the combined prediction model demonstrated optimal diagnostic performance with AUC of 0.943 and 0.967, respectively.ConclusionsThe combined predictive model based on volumetric quantitative analysis in DECT offers valuable information to discriminate immunohistochemical expression status, facilitating clinical decision-making for patients with NSCLC.

Comparison of tucidinostat with CHOP-like versus CHOP-like in first-line treatment of peripheral T-cell lymphoma: a single-center real-world study.

Tucidinostat has been approved by the Chinese FDA for relapsed/refractory Peripheral T cell lymphoma (PTCL), but its efficacy in newly diagnosed PTCL has not been confirmed. In this study, we aimed to compare the efficacy of tucidinostat combined with CHOP-like (C + CHT) versus CHOP-like alone (CHT) in newly diagnosed PTCL patients. Of the PTCL patients, 109 were newly diagnosed. Patients in the C + CHT group who achieved objective response received tucidinostat maintenance therapy. A total of 36 pairs (n = 72) were matched at a ratio of 1:1 using propensity scoring. The matching criteria included: whether the Prognostic index for the peripheral T-cell lymphoma-not otherwise specified subtype (PIT) was ≥ 2, the pathological subtype, age > 60 years, and gender (matching tolerance = 0.024). A significantly higher objective response rate (ORR) (P = 0.016), 2-year progression-free survival (PFS) (P = 0.026), and 2-year survival rate (P = 0.017) was observed for the C + CHT group as compared to the CHT group. After propensity score matching (PSM), the C + CHT group as compared to the CHT group displayed significantly longer PFS (P = 0.035) and overall survival (OS) (P = 0.029). For the C + CHT group in the per-protocol set, the effect values showed a significant benefit in terms of both PFS (P = 0.027) and OS (P = 0.019). Common grade 3-4 haematological adverse events (AEs), had comparable incidence in each group; while common non-haematological AEs, including elevated AST and ALT were higher in the C + CHT group than in the CHT group. Our study suggests that the tucidinostat with CHOP-like regimen and sequential tucidinostat maintenance after objective remission provides a promising therapeutic approach for treating newly diagnosed PTCL patients.

Potentials of pretreatment [18F]FDG PET/CT for non-invasive prediction of the tumor unfavorable pathological indices and microenvironment in NSCLC

PurposeTo investigate pretreatment [18F]FDG PET/CT in predicting tumor pathological features and microenvironment.MethodologyFifty-one patients with histo-pathologically proven non-small cell lung cancer (NSCLC) underwent pretreatment [18F]FDG PET/CT, and their clinicopathological data were collected. PET-derived biomarkers (SUVmax, mean, MTV, and TLG), consolidation-to-tumor ratio (CTR), and histopathological data (tumor grade, differentiation, tumor histological subtype, tumor-infiltrating lymphocytes (TILs), degree of desmoplasia, degree of necrosis, tumor budding, and nuclear grade), as well as a proposed risk stratification pathological scoring system, were all assessed.ResultsA CTR cut-off point of 0.34 was able to discriminate between low- and high-grade tumors with a sensitivity and specificity of 75.9% and 68.2%, respectively (p = 0.012). Low CTR was significantly associated with the tumor pathological subtype “adenocarcinoma,” low nuclear grade, negative tumor necrosis, and low pathological scores, respectively (p < 0.05). No significant associations were observed for CTR with tumor budding score, desmoplasia score, or TILs% (p-values > 0.05). High SUVmax (> 12.64) and high SUVmean (> 4.28) values were significantly associated with SCC tumors (p = 0.023 and 0.04, respectively). SUVmean was significantly associated with cytological differentiation (p = 0.023). A statistical trend was noted for SUVmax concerning nuclear grade and desmoplasia scores (p = 0.068 and 0.061, respectively). No statistically significant associations were revealed for MTV and TLG concerning different pathological features (p-values > 0.05). Primary lung tumors positive for desmoplasia revealed higher metabolic activity regarding SUVmax, with a statistical trend observed (p = 0.072). No statistically significant associations were observed concerning other metabolic parameters (p-values > 0.05).ConclusionPET/CT-derived biomarkers appear promising for predicting tumor unfavorable pathological features and microenvironment in NSCLC.

Nomogram predicts cervical lymph node metastasis of pathological subtypes of papillary thyroid carcinoma.

Pathological subtypes of papillary thyroid carcinoma (PTC) are important factors in thyroid cancer. Some rare subtypes exhibit extensive lymph node metastasis. These pathological subtypes should receive more attention in clinical practice. Patients with different pathological subtypes of PTC were selected from the SEER database. Logistic regression, random forest, and bootstrap aggregating (bagging) methods were employed to screen for risk factors associated with cervical lymph node metastasis in the training cohort. A nomogram was established based on the model with the largest area under the curve (AUC) and evaluated using calibration curves. Decision curve analysis (DCA) was used to evaluate the clinical benefit to patients. The nomogram was validated in depth by 200 iterations of tenfold cross-validation. A total of 7,882 patients were included in the analysis, with 5,516 patients in the training group and 2,366 patients in the testing group. The logistic regression model achieved the highest AUC of 0.7396. Sex, age, race, extension (extrathyroidal extension), pathological type, and primary tumour size were identified as independent risk factors for cervical lymph node metastasis (p < 0.05). The calibration curve indicated that the model was well calibrated. DCA indicated that the nomogram model had good clinical practicability. In clinical practice, it is important to consider the pathological subtypes of PTC. The established nomogram can serve as a predictive tool for assessing cervical lymph node metastasis.

Interleukin-6 transcripts up-regulation in lymph nodes from unicentric and multicentric Castleman disease.

Castleman disease (CD) represents a spectrum of heterogeneous lymphoproliferative disorders sharing peculiar histopathological features, clinically subdivided into unicentric CD (UCD) and multicentric CD (MCD) and presenting with variable inflammatory symptoms. Interleukin (IL)-6 and other cytokines play a major role in mediating CD inflammatory manifestations. Although the local microenvironment seems to be among the major sources of hypercytokinemia, the precise cellular origin of IL-6 production in CD is still debated. A series of five nodal CD of different subtypes (one UCD, two idiopathic MCDs [iMCDs], one HIV-negative human herpesvirus 8 (HHV8)-associated MCD, and one HIV-positive HHV8-associated MCD) and a non-CD reactive control were tested using RNAscope analysis and a dual in situ hybridization (ISH)/immunohistochemistry technique, in order to quantify IL-6 expression and its spatial distribution. Quantitative analyses of in situ mRNA were performed on digitalized slides using the HISTOQUANT software (3DHISTECH) and differences between cases were evaluated by the Kruskal-Wallis test. RNA-ISH documented increased IL-6 expression in all CD lymph nodes, independently from clinical and pathological subtypes, however, the highest levels were found in HHV8+ cases and statistically significant differences in IL-6 expression were found only between HHV8+ MCD and control case. Dual RNA-ISH for IL6 coupled with immunohistochemistry analysis showed that IL-6 was overexpressed in CD31-positive endothelial cells in 5/5 CD tested cases but not in the control case. Our findings suggest that nodal IL-6 expression seems to be significantly upregulated in HHV8+ MCD, but a trend toward increased nodal IL-6 expression was noticed also in UCD and iMCD-not otherwise specified. CD31+ endothelial cells probably represent one of the major sources of IL-6 production in the nodal microenvironment.

Ensemble transformer-based multiple instance learning to predict pathological subtypes and tumor mutational burden from histopathological whole slide images of endometrial and colorectal cancer

In endometrial cancer (EC) and colorectal cancer (CRC), in addition to microsatellite instability, tumor mutational burden (TMB) has gradually gained attention as a genomic biomarker that can be used clinically to determine which patients may benefit from immune checkpoint inhibitors. High TMB is characterized by a large number of mutated genes, which encode aberrant tumor neoantigens, and implies a better response to immunotherapy. Hence, a part of EC and CRC patients associated with high TMB may have higher chances to receive immunotherapy. TMB measurement was mainly evaluated by whole-exome sequencing or next-generation sequencing, which was costly and difficult to be widely applied in all clinical cases. Therefore, an effective, efficient, low-cost and easily accessible tool is urgently needed to distinguish the TMB status of EC and CRC patients. In this study, we present a deep learning framework, namely Ensemble Transformer-based Multiple Instance Learning with Self-Supervised Learning Vision Transformer feature encoder (ETMIL-SSLViT), to predict pathological subtype and TMB status directly from the H&E stained whole slide images (WSIs) in EC and CRC patients, which is helpful for both pathological classification and cancer treatment planning. Our framework was evaluated on two different cancer cohorts, including an EC cohort with 918 histopathology WSIs from 529 patients and a CRC cohort with 1495 WSIs from 594 patients from The Cancer Genome Atlas. The experimental results show that the proposed methods achieved excellent performance and outperforming seven state-of-the-art (SOTA) methods in cancer subtype classification and TMB prediction on both cancer datasets. Fisher’s exact test further validated that the associations between the predictions of the proposed models and the actual cancer subtype or TMB status are both extremely strong (p<0.001). These promising findings show the potential of our proposed methods to guide personalized treatment decisions by accurately predicting the EC and CRC subtype and the TMB status for effective immunotherapy planning for EC and CRC patients.

18Fluorodeoxyglucose positron emission tomography (18F-FDG PET)–derived tumoral and peritumoral radiomic parameters can predict pathological subtype and survival in esophageal carcinoma

The aim of this study is to investigate the importance of the quantitative parameters of the tumoral and peritumoral regions in prediction of pathological subtypes and 1-year survival in patients with esophageal carcinoma. A total of 103 patients with esophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC) and in whom 18fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) was performed were included in the study. One-year progression-free survival (PFS) and overall survival times of all patients were noted. Primary tumor and peritumoral area were drawn with manual segmentation on the 18F-FDG PET images. Seventy-three quantitative parameters were extracted from tumoral and peritumoral volumes of interest by using software. The differences of parameters of tumoral and peritumoral regions were determined statistically between pathological subtypes and between 1-year survivors and non-survivors. Diagnostic models were created with the statistically significant parameters. The model that consists of a tumoral and a peritumoral parameter could classify the pathological subtypes in 61% of the patients correctly (area under the curve [AUC]: 0.706, 61.2% accuracy, 53.7% sensitivity, and 75% specificity). The model that was created with 2 tumoral parameters could classify the 1-year survival in 66% of the patients correctly (AUC: 0.695, 66% accuracy, 73.6% sensitivity, and 56.1% specificity). The model consisting of a tumoral and a peritumoral parameter detected 1-year PFS in 66% of the patients accurately (AUC: 0.687, 66% accuracy, 72.4% sensitivity, and 55.6% specificity). The quantitative parameters obtained from tumoral and peritumoral regions can provide information about pathological subtypes and 1-year survival in esophageal carcinoma.

Artemisitene induces apoptosis of breast cancer cells by targeting FDFT1 and inhibits the growth of breast cancer patient-derived organoids

Artemisitene (ATT) is a natural bioactive compound with anti-breast cancer activity. However, the direct target and clinical efficacy of ATT on breast cancer are still unclear. The current study aimed to identify the target protein and underlying mechanism of ATT in anti-breast cancer. Moreover, patient-derived organoids (PDOs) were employed to assess the clinical efficacy of ATT on breast cancer. Herein, molecular docking, molecular dynamics simulation, cellular thermal shift assay (CETSA) combined with Western blot, surface plasmon resonance (SPR) were applied to confirm the interactional target of ATT in breast cancer cells. Bioinformatics analysis, Western blot, flow cytometry, plasmid construction and lentivirus infection, chromatin immunoprecipitation (ChIP) assay, and quantitative real-time PCR (RT-qPCR) were performed to reveal the potential mechanism of ATT in treating breast cancer. PDOs were established to evaluate the clinical therapeutic efficiency of ATT on breast cancer. We found that ATT interacted with Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) in breast cancer cells. Knockdown of FDFT1 induced NEDD4 expression and apoptosis in breast cancer cells. Overexpression of FDFT1 could rescue ATT-induced apoptosis, while interfering with FDFT1 expression decreased the level of RelA (NF-κB p65 subunit) in the nucleus in breast cancer cells. Knockdown of FDFT1 induced NEDD4 expression by regulating TNFR1/NF-κB pathway. Overexpression of FDFT1 could reverse the activation of ATT-induced TNFR1/NF-κB/NEDD4 pathway in breast cancer cells. Interestingly, the ChIP assay and RT-qPCR revealed that p65 could regulate NEDD4 transcription. Furthermore, ATT exhibited a broad-spectrum inhibitory effect on the growth of breast cancer PDOs with different pathological subtypes, and showed an excellent safety profile in comparison with that of conventional chemotherapy drugs. In summary, this work demonstrated that ATT targets FDFT1 to induce apoptosis of breast cancer cells through regulating TNFR1/NF-κB/NEDD4 pathway and suppresses breast cancer PDOs growth, which supported ATT as an effective and potential drug candidate for breast cancer treatment.