Poor Differentiation Research Articles

Annexin A5 is a novel prognostic biomarker in oral squamous cell carcinoma.

ANXA5, a notable tumor marker, displays irregular expression in diverse solid cancers, and links to local recurrence and metastasis rates. We aimed study the expression of ANXA5 in oral squamous cell carcinoma (OSCC) and its diagnostic and prognostic values. 520 head and neck squamous cell carcinoma (HNSCC) patients in TCGA database and 124 OSCC patients in Nanjing stomatology hospital were enrolled in our study. Immunohistochemical analyses were performed using ANXA5 antibodies. Chi-square test was used to analyze the clinicopathological features. Survival rates were determined using the Kaplan-Meier method and log-rank test. Our results showed significantly elevated ANXA5 at the gene and protein levels in HNSCC and OSCC compared to non-tumor tissues. Histopathologically, ANXA5 was broadly present in OSCC tumor cells and fibroblast-like cells but absent in tumor-infiltrating lymphocytes, particularly at the invasive tumor front. Patients exhibiting high ANXA5 expression in these cells demonstrated poor differentiation, aggressive invasion patterns, and heightened lymph node metastasis risk, contributing to poorer postoperative outcomes. Remarkably, ANXA5 in fibroblast-like cells emerged as an independent risk factor impacting survival in OSCC patients. Gene set enrichment analysis (GSEA) highlighted ANXA5's involvement in key pathways like epithelial-mesenchymal transformation (EMT), TGF-beta signaling, and hypoxia, which correlated with adverse clinical outcomes in OSCC. ANXA5 emerges as a significant prognostic biomarker for OSCC, potentially influencing its metastasis via the EMT pathway.

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasm and derivation of a prognostic model: An international multicenter study (ADENO-IPMN study)

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival. Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed. In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00). A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.

Analysis of Th1/Th2 cytokine profile and clinical characteristics of patients with head and neck squamous cell carcinoma.

Immune system biomarkers in cancer pathogenesis offer new therapeutic avenues, as seen in cytokine (CK) profiles of laryngeal and hypopharyngeal tumors. A retrospective analysis was conducted on 58 patients with laryngeal and hypopharyngeal tumors and 27 patients with benign vocal cord lesions to explore the role of serum CKs in these diseases' characteristics and immunotherapy. The differences in the levels of 12 cytokines were measured. Additionally, the study examined the correlation between T helper cells (Th)1/Th2 cytokine levels and the clinical characteristics and immunotherapy efficacy of laryngeal and hypopharyngeal cancers. The results show that the balance of Th1/Th2 is biased towards Th2 in patients with laryngeal and hypopharyngeal tumors. Among these, interleukin (IL)-6 (P = 0.021) was highly expressed in laryngeal tumors, and the expression levels of IL-1β (P = 0.008), IL-6 (P = 0.005), and IL-8 (P = 0.05) were higher in patients with poorly differentiated laryngeal tumors. The level of IL-4 (P = 0.0048) was significantly correlated with tumor location. The expression levels of IL-2 (P = 0.010), IL-4 (P = 0.028), IL-10 (P = 0.011), IL-12p70 (P = 0.034), IL-17 (P = 0.024), tumor necrosis factor (TNF)-α (P = 0.003), and interferon (IFN)-γ (P = 0.007) were related to lymph node metastasis. The level of IFN-γ (P = 0.016) was correlated with the efficacy of neoadjuvant therapy, while the level of IFN-α (P = 0.013) was significantly correlated with programmed death ligand 1 (PD-L1) expression. The Principal Component Analysis (PCA) results showed that patients with tumors, poor differentiation, and lymph node metastasis had higher levels of Th1 and Th2 cytokine separation. In conclusion, the shift in the balance of Th1 and Th2 cytokine expression indicates higher tumor invasiveness, and IFN has potential as a circulating molecular marker for immunotherapy of head and neck squamous cell carcinoma.

Improved prenatal assessment of kidney disease using multiple ultrasound features.

Congenital anomalies of the kidney and the urinary tract (CAKUT), often discovered in utero, cover a wide spectrum of outcomes ranging from normal postnatal kidney function to fetal death. The current ultrasound workup does not allow for an accurate assessment of the outcome. The present study aimed to significantly improve the ultrasound-based prediction of postnatal kidney survival in CAKUT. Histological analysis of kidneys of 15 CAKUT fetuses was performed to better standardize the ultrasound interpretation of dysplasia and cysts. Ultrasound images of 140 CAKUT fetuses with 2-year postnatal follow-up were annotated for amniotic fluid volume and kidney number, size, dysplasia and/or cysts using standardized ultrasound readout. Association of ultrasound features and clinical data (sex and age at diagnosis) with postnatal kidney function was studied using logistic regression. Amniotic fluid proteome associated to kidney dysplasia or cysts was characterized by mass spectrometry. Histologically, poor ultrasound corticomedullary differentiation was associated to dysplastic lesions and ultrasound hyperechogenicity was associated to the presence of microcysts. Of all ultrasound and clinical parameters, reduced amniotic volume, dysplasia and cysts were the best predictors of poor outcome (Odd ratio = 57 [95%CI: 11-481], 20 [3-225] and 7 [1-100], respectively). Their combination into an algorithm improved prediction of postnatal kidney function compared to amniotic volume alone (area under the ROC curve = 0.92 [0.86-0.98] in a 10-fold cross validation). Dysplasia and cysts were correlated (Cramer's V coefficient = 0.44, p<0.0001), but amniotic fluid proteome analysis revealed that they had distinct molecular origin (extracellular matrix and cell contacts versus cellular death, respectively), probably explaining the additivity of their predictive performances. Antenatal clinical advice for CAKUT pregnancies can be improved by a more standardized and combined interpretation of ultrasound data.

Residual biliary intraepithelial neoplasia without malignant transformation at resection margin for perihilar cholangiocarcinoma does not require expanded resection: a dual center retrospective study

BackgroundAdditional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN).MethodConsecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics.Results306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup.ConclusionFor pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.

Abdominal aortic calcification volume as a preoperative prognostic predictor for pancreatic cancer.

Atherosclerosis and cancer may progress through common pathological factors. This study was performed to investigate the association between the abdominal aortic calcification (AAC) volume and outcomes following surgical treatment for pancreatic cancer. The subjects of this retrospective study were 194 patients who underwent pancreatic cancer surgery between 2007 and 2020. The AAC volume was assessed through routine preoperative computed tomography. Univariate and multivariate analyses were performed to evaluate the impact of the AAC volume on oncological outcomes. A higher AAC volume (≥ 312 mm3) was identified in 66 (34%) patients, who were significantly older and had a higher prevalence of diabetes and sarcopenia. Univariate analysis revealed several risk factors for overall survival (OS), including male sex, an AAC volume ≥ 312 mm3, elevated carbohydrate antigen 19-9, prolonged operation time, increased intraoperative bleeding, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy. Multivariate analysis identified an AAC volume ≥ 312 mm3, prolonged operation time, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy as independent OS risk factors. The OS rate was significantly lower in the high AAC group than in the low AAC group. The AAC volume may serve as a preoperative prognostic indicator for patients with pancreatic cancer.

Deep Learning Classification and Quantification of Pejorative and Nonpejorative Architectures in Resected Hepatocellular Carcinoma from Digital Histopathologic Images

Liver resection is one of the best treatments for small hepatocellular carcinoma (HCC), but post-resection recurrence is frequent. Biotherapies have emerged as an efficient adjuvant treatment, making the identification of patients at high risk of recurrence critical. Microvascular invasion (mVI), poor differentiation, pejorative macrotrabecular architectures, and vessels encapsulating tumor clusters architectures are the most accurate histologic predictors of recurrence, but their evaluation is time-consuming and imperfect. Herein, a supervised deep learning-based approach with ResNet34 on 680 whole slide images (WSIs) from 107 liver resection specimens was used to build an algorithm for the identification and quantification of these pejorative architectures. This model achieved an accuracy of 0.864 at patch level and 0.823 at WSI level. To assess its robustness, it was validated on an external cohort of 29 HCCs from another hospital, with an accuracy of 0.787 at WSI level, affirming its generalization capabilities. Moreover, the largest connected areas of the pejorative architectures extracted from the model were positively correlated to the presence of mVI and the number of tumor emboli. These results suggest that the identification of pejorative architectures could be an efficient surrogate of mVI and have a strong predictive value for the risk of recurrence. This study is the first step in the construction of a composite predictive algorithm for early post-resection recurrence of HCC, including artificial intelligence-based features.

Impact of bulky loco-regional lymphadenopathy in esophageal adenocarcinoma on survival: a retrospective single center analysis.

The relationship between 'bulky' locoregional lymphadenopathy and survival has not been investigated in the setting of esophageal adenocarcinoma (EAC). This study aimed to explore whether bulky regional lymphadenopathy at diagnosis affected survival outcomes in patients with EAC treated with neoadjuvant chemotherapy and en bloc resection. A single-center retrospective review of a prospectively maintained upper GI cancer surgical database was performed between January 2012 and December 2019. Patients with locally advanced EAC (cT2-3, N+, M0) treated with neoadjuvant docetaxel-based chemotherapy and transthoracic en bloc esophagogastrectomy were identified. Computed tomography scans from before the initiation of treatment were reviewed, and patients were stratified according to whether bulky loco-regional lymph nodes were present. This was defined as lymphadenopathy >2cm in any axis. Overall survival was compared, and a Cox multivariate regression model was calculated. Two hundred twenty-five of the eight hundred seventy patients identified met the inclusion criteria. Forty-eight (21%) had bulky lymphadenopathy, leaving 177 allocated to the control group. More patients with bulky lymphadenopathy had ypN3 disease (18/48, 38% vs. 39/177, 20%, P = 0.025). Among patients with bulky lymphadenopathy, overall survival was generally worse (32.6 vs. 59.1months, P = 0.012). However, among the 9/48 (19%) patients with bulky lymphadenopathy who achieved ypN- status survival outcomes were similar to those with non-bulky lymphadenopathy who also achieved lymph node sterilization. Poor differentiation (HR 1.8, 95% CI 1.0-2.9, P = 0.034), ypN+ (HR 1.9, 95% CI 1.1-3.6, P = 0.032), and bulky lymphadenopathy were independently associated with an increased risk of death (HR 1.7, 1.0-2.9, P = 0.048). Bulky regional lymphadenopathy is associated with a poor prognosis. Efforts to identify the ideal treatment regimen for these patients are urgently required.

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study.

Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

Genomic Landscape of Adenocarcinomas Across the Gastroesophageal Junction: Moving on from the Siewert Classification.

To investigate how the Siewert classification of gastroesophageal junction adenocarcinomas correlates with genomic profiles. Current staging and treatment guidelines recommend that tumors with an epicenter less than 2cm into the gastric cardia be treated as esophageal cancers, while tumors with epicenter greater than 2cm into the cardia be staged and treated as gastric cancers. To date, however, few studies have compared the genomic profiles of the 3 Siewert classification groups to validate this distinction. Using targeted tumor sequencing data on patients with adenocarcinoma of the gastroesophageal junction previously treated with surgery at our institution, we compared genomic features across Siewert classification groups. A total of 350 patients were included: 121 had Siewert type I, 170 type II, and 59 type III. Comparisons by Siewert location revealed that Siewert type I and II were primarily characterized as the chromosomal instability (CIN) molecular subtype and displayed Barrett's metaplasia and p53 and cell cycle pathway dysregulation. Siewert type III tumors, by contrast, were more heterogeneous, including higher proportions of microsatellite instability (MSI) and genomically stable (GS) tumors and more frequently displayed ARID1A and somatic CDH1 alterations, signet ring cell features, and poor differentiation. Overall, Siewert type I and II tumors demonstrated greater genomic overlap with lower esophageal tumors, while Siewert type III tumors shared genomic features with gastric tumors. Overall, our results support recent updates in treatment and staging guidelines. Ultimately, however, molecular rather than anatomic classification may prove more valuable in determining staging, treatment, and prognosis.

Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

The Role of Elective Nodal Irradiation in Treating Clinically Node-Negative Sinonasal Squamous Cell Carcinoma

PurposeThis study aims to examine the role of elective nodal irradiation (ENI) in clinically node-negative (cN0) sinonasal squamous cell carcinoma (SNSCC) and to define the optimal radiation fields for ENI. Methods and MaterialsWe retrospectively reviewed 368 cN0 SNSCC patients treated between 2009 and 2021. The study evaluated the impact of ENI on overall survival (OS), progression-free survival (PFS), regional-failure-free survival (RFS), and distant metastasis-free survival (DMFS), along with the coverage areas of ENI. ResultsThe majority of patients underwent surgery (n=316, 85.9%), with 75% (n=276) having tumors in the maxillary sinus or nasal cavity and 67.7% (n=249) presenting with T4 disease. Additionally, 32.3% (n=119) of the tumors were poorly differentiated. The 5-year OS, PFS, RFS, and DMFS rates were 59.3%, 54.0%, 57.6%, and 58.8%, respectively. ENI was performed in 217 patients (59%), with sixteen experiencing neck relapse during follow-up. While ENI did not enhance survival rates, it significantly reduced the overall regional-failure rate (7.9% vs. 1.8%, χ2 =7.98, p<0.01) and the cumulative incidence of regional failure (p=0.045). Additionally, the subgroups with maxillary sinus origin (2.33% vs. 13.51%, p=0.025), T4 stage (1.80% vs. 8.54%, p=0.028), and poor differentiation (2.44% vs. 13.51%, p=0.029) had higher cumulative incidences of regional failure in patients without ENI. No significant difference was observed in survival and regional failure rates between patients treated with ENI to levels Ib and II with or without level III, as well as between cN0 patients with non-midline crossing lesions receiving unilateral or bilateral ENI. ConclusionsDespite no survival benefit, ENI significantly decreases the regional failure rate in cN0 SNSCC patients. For primary lesions not crossing the midline, ipsilateral ENI targeting levels Ib and II proves to be an effective strategy.

The histopathological spectrum and molecular changes associated with KRAS G12C mutation in non-small cell lung carcinoma

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.

Efficacy and safety of donafenib as adjuvant therapy for patients with hepatocellular carcinoma undergoing curative resection: A retrospective, multicenter cohort study.

e16234 Background: A growing incidence of hepatocellular carcinoma and its high risk of recurrence after curative-intent treatment underscore the need for effective adjuvant treatment options. This study aimed to assess the efficacy of adjuvant donafenib in patients with hepatocellular carcinoma (HCC) following radical resection. Methods: This multicenter, real-world study retrospectively gathered clinical data of 82 patients who had undergone radical resection of HCC and received adjuvant therapy with donafenib. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analysis was performed to evaluate RFS and OS, while the Cox proportional-hazards model was used to estimate risk factors for tumor recurrence and death. Results: A total of 82 patients with HCC who received donafenib following surgical resection were included in the study, of which were classified as high risk for tumor recurrence (with multiple or large tumor, microvascular invasion, poor tumor differentiation). The median duration of donafenib adjuvant therapy was 10.6 months (range: 0.2–26.1 months). All patients completed follow-up as required, with a median follow-up time of 19.4 months (range: 2.8–57.6 months). During the follow-up period, a totally postoperative recurrence rate was 15.9% (13/82). 1-year recurrence rate and 2-year recurrence rate were 7.3% (6/82) and 12.2% (10/82), and 1-year survival rate and 2-year survival rate were 95.1% (78/82) and 93.9% (77/82). Kaplan-Meier analysis demonstrated that patients with higher preoperative AFP level (AFP &gt; 400ng/mL), higher preoperative PIVKA-II level (PIVKA-II &gt; 40mAU/mL), or poor tumor differentiation (Edmondson stage III-IV) exhibited higher rate of tumor recurrence after operation (all p value &lt; 0.05). Multivariate analysis indicated that preoperative AFP level was an independent risk factor for tumor recurrence in patients with donafenib treatment. Treatment-related adverse events (TRAEs) occurred in 67.1% (55/82) of patients, of which the most frequent were hand-foot syndrome (25.6%, 21/82), diarrhea (20.7%, 17/82), and fatigue (17.1%, 14/82). Only 8.5% (7/82) of patients had a grade ≥3 TRAEs, with the most common being hand-foot syndrome (2.4%, 2/82) and hypertension (2.4%, 2/82). No treatment-related deaths were reported. Conclusions: This study represents the largest multicenter investigation of adjuvant therapy with donafenib to date, and the findings indicate that donafenib has the potential to be an effective treatment option for preventing postoperative recurrence in HCC. Furthermore, the preoperative AFP ≤400ng/mL can serve as an effective biomarker for postoperative administration of donafenib in HCC patients.

The Association Between Immune-Histochemical Expressions of Program Death Ligand with some Aggressive Features of Prostate Cancer

Prostate cancer (PC), accounts for more than one-fourth of all cancer diagnoses, and the most frequently diagnosed cancer among men in 2022. The immunoglobulin (IG) Program death ligand-1(PD-1) cell surface receptor is predominantly expressed on the surface of many cells. The purpose of this study was to demonstrate the relationship between Program death ligand expression and some aggressive features of prostate cancer including perineural invasion, vascular invasion and necrosis. Thirty cases of prostate cancer with age range from 60 to 80 year old and 30 cases of normal prostate tissue with age under 25 year old were separated into two groups in a retrospective case-control research that encompassed 60 cases. All malignant cases were examined by consultant pathologists for the diagnosis of prostate carcinoma, and each block of tissue was divided into two slides, one for hematoxylin and eosin (H&amp;E) staining and the other for immunoglobulin (IHC) staining of PDL-1. The expression pattern of Program Death Ligand was investigated in these samples and its relationship to particular clinic-pathological characteristics. Despite it was not expressed in healthy prostatic tissue, program death ligand demonstrated to be positive in prostate cancer with vascular invasion, perineural invasion, and necrosis, while it was negative in healthy prostatic tissue. High expression of Program death ligand was correlated with poor differentiation, neural invasion, and vascular invasion; these criteria indicate that the expression of Program death ligand is associated with high grade and aggressive tumors. The current study confirms that perineural invasion, vascular invasion, and necrosis are all accompanied by a rise in Program death ligand expression regardless their grade and stage

Prognostic significance of real-world (RW) recurrence patterns after resection or ablation of early-stage hepatocellular carcinoma (HCC): Insights from the US Medicare population.

e16241 Background: The prognosis after curative-intent resection or ablation of early-stage HCC remains poor, largely due to high rates of recurrence. We aimed to characterize real-world recurrence patterns and determine whether the timing of recurrence was associated with overall survival (OS). Methods: Patients (pts) with early-stage HCC who underwent resection and/or ablation were identified from the SEER-Medicare database (2010-2019). Pts who received liver transplant were excluded. A proxy for recurrence was defined as the receipt of new HCC treatments (surgery, locoregional therapy, systemic therapy) or a secondary malignant neoplasm claim (excluding liver). Pseudo-recurrence dates were assigned to pts without recurrence to match the distribution of time between initial resection/ablation and recurrence in the recurrence cohort, to avoid immortal time bias. Early vs late recurrence was defined as occurring within 1 year vs after 1 year of initial resection/ablation. Primary outcome was OS as measured both from the time of recurrence/pseudo-recurrence and initial resection/ablation. Results: 1,146 eligible pts with early-stage HCC were identified. 63% were male, mean age was 74 yrs, and initial therapy was resection (39%), ablation (50%), or both (11%). 736 (64%) experienced recurrence. Among them, 53% received ablation, 37% surgery, and 11% received both. Median OS from recurrence or pseudo-recurrence was 22 months (mo) vs 67 mo (p &lt; 0.001) for pts with vs without recurrence, respectively. When measured from resection/ablation date, median OS was 39 mo vs 83 mo (p &lt; 0.001). After adjusting for relevant demographic and clinico-pathologic factors, including type of index therapy, in a multivariable Cox regression model, recurrence remained significantly associated with an increased risk of death (hazard ratio [HR]: 2.24; 95% CI: 1.85-2.71; p &lt; 0.001). Among pts who recurred, 380 (52%) had early recurrence and 356 (48%) had late recurrence. Median OS from recurrence was 17 mo vs 30 mo (p &lt; 0.001) for early vs late recurrence, respectively, and 23 mo vs 63 mo when measured from resection/ablation The adjusted HR for the risk of death associated with early recurrence was 1.39 (95% CI: 1.14-1.68; p &lt; 0.001) compared to late recurrence. Other significant prognostic factors associated with reduced OS included larger tumor size ( &gt; = 5cm), greater extent of disease, and poor differentiation (grade III and above). Conclusions: In this study among US Medicare pts, early recurrence within one year after curative-intent treatment of early-stage HCC was significantly associated with decreased OS compared to pts who recur later or without recurrence. This highlights the need for developing and utilizing effective adjuvant therapy regimens to delay or avoid recurrence.

Performance of surufatinib in treating advanced neuroendocrine neoplasms: Insights from a real-world study.

e15124 Background: Current comparisons of targeted treatments for advanced neuroendocrine neoplasms (NENs)-specifically surufatinib, sunitinib, and everolimus—are lacking. This study aims to assess their efficacy and safety in a real-world setting. Methods: A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs prescribed surufatinib, sunitinib or everolimus between July 2020 and April 2023. The primary outcome was median progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR) and adverse events (AE). Results: A total of 123, 56 and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib or everolimus were enrolled. In pancreatic NENs (pNEN), surufatinib demonstrated superior efficacy over sunitinib and everolimus combined (mPFS: 8.67 vs 6.37 months, P=0.02; ORR: 17.1% vs 8.3%). Specifically, surufatinib outperformed sunitinib (mPFS: 8.67 vs 6.40 months, P=0.04; ORR: 17.1% vs 10.9%) and everolimus (mPFS: 8.67 vs 5.37 months, P=0.05; ORR: 17.1% vs 3.8%) individually. In extrapancreatic NENs (epNEN), surufatinib showed enhanced efficacy compared to everolimus (mPFS: 9.47 vs 6.70 months, P=0.15; ORR: 8.3% vs 5.3%). On multivariate Cox analysis, male, functional status, Ki67 index&gt;20%, previous SSA and germline mutation, poor differentiation, liver metastasis, multi treatment lines were identified as negative effect (P&lt;0.05) for PFS in pNEN and epNEN patients respectively. The most common adverse events (AEs) were hypertension (12.2%) in surufatinib-treated patients, manageable with medication. Sunitinib led to decreased neutrophil counts (10.7%), and everolimus was associated with anemia (4.4%). Conclusions: Utilizing real-world data, this study reveals surufatinib significantly enhances progression-free survival (PFS) over sunitinib and everolimus in advanced neuroendocrine neoplasms (NENs), guiding future targeted treatment choices.

Clinicopathological features and genomic profiles of prostate cancer with elevated carbohydrate antigen 19-9.

e17003 Background: The elevated carbohydrate antigen 19-9 (CA199) is commonly observed in digestive system tumors, but rarely in prostate cancer (PCa). Due to the rarity and the poor understanding of the special subtype of PCa, the clinicopathological and genomic characteristics and survival outcomes in PCa patients with elevated CA199 in our center were analyzed. Methods: Cases were collected retrospectively from 2012 to 2023 in Sun Yat-sen University Cancer Center. The tumor genomic profiles were analyzed by R (http://www.rproject.org). Kaplan-Meier survival analyses were performed to compare survival outcomes. All statistical analyses were performed using SPSS version 26.0 and GraphPad Prism version 8.0. All analyses were two‐tailed, and the significance level was set at P&lt;0.05. Results: A total of 137 PCa patients with elevated CA199 (&gt;35ng/ml) were identified, with an exclusion of 47 patients with secondary cancers and 40 patients with other diseases that may cause elevated CA199, finally 50 cases (22 with primary and 28 with secondary elevated CA199) were included. The median initial PSA and the median time from diagnosis to CRPC were 102ng/ml and 14 months. Most patients were with a high GS score (GS≥8: 82%) and an advanced stage (M1: 84%). Poorly differentiated adenocarcinoma (22%) was frequently observed. Compared with patients with primary elevated CA199, patients with secondary elevated CA199 had higher levels of CA199 (102ng/ml vs. 78ng/ml, p=0.0456), lower levels of PSA at diagnosis (65ng/ml vs. 132ng/ml, p=0.0131) and higher proportion of poorly differentiated adenocarcinoma (36% vs. 5%, p=0.0138). The level of CA199 in patients with primary elevated CA199 was correlated with the level of CEA (R2=0.2658, p=0.0168), but not with the level of NSE or PSA. At a median follow-up of 31 months, the median OS of the whole group, primary elevated CA199 and secondary elevated CA199 subgroups was 49 months, 31 months and not reached. Secondary elevated CA199 (p=0.0009), abiraterone treatment (p&lt;0.0001) and chemotherapy treatment (p=0.0331) were significant prognostic factors of OS. To study the genomic characteristics of PCa patients with elevated CA199, 29 PCa patients with normal CA199 were included as a control (genomic data available in 13 and 29 cases respectively). Patients with elevated CA199 were more likely to have mutations in castration resistant associated genes (AR, FOXA1, ASXL1, KMT2B, JAK2 and AKT1), malignant progression associated genes (RARA, BLM, PIK3R1) and CA199 metabolism associated gene (ERBB2). Conclusions: PCa with elevated CA199 is highly malignant and with poor prognosis. Intensive treatment with abiraterone and chemotherapy could benefit such patients. Poor pathological differentiation and the gene mutation profile may partly explain the clinical outcome.

Surgical and endoscopic management of clinical T1b esophageal cancer

ObjectiveEsophageal cancers that invade the submucosa (T1b) have increased risk for occult lymph node metastases. To avoid the morbidity and recovery from esophagectomy, patients with cT1bN0 tumors have been increasingly managed endoscopically. We hypothesized that tumor attributes could predict upstaging and outcome associated with surgical and endoscopic treatment. Our objective was to evaluate the comparative effectiveness of esophagectomy across different cT1bN0 tumor attributes. MethodsTreatment-naïve patients who underwent endoscopic management or esophagectomy for a clinical stage cT1bN0 esophageal cancer diagnosed between 2010 and 2018 in the National Cancer Database were identified. Factors associated with upstaging were assessed by logistic regression. Adjusted survival was assessed by Kaplan-Meier analysis of 528 propensity-matched pairs and accelerated time failure models, stratified across tumor attributes. ResultsOverall, 1469 patients classified as cT1bN0 were identified; 926 underwent esophagectomy and 543 were managed endoscopically. In general, patients who were managed endoscopically were older (median, 71; interquartile range, 63-78; vs 66; interquartile range, 60-72; P < .0001) with smaller tumors compared with the patients who were managed with esophagectomy. Nodal upstaging was associated with lymphovascular invasion (odds ratio [OR], 6.88; confidence interval [CI], 4.39-10.77; P < .0001), poor tumor differentiation (OR, 2.77; CI, 1.30-5.88; P = .0081), and tumor size >1 cm (OR, 3.19; CI, 1.49-6.83, P = .0028). Overall survival was better among propensity-matched patients who underwent esophagectomy (5-year 68.4% vs 59.7% endoscopic, P < .001). However, accelerated time failure models suggested similar outcomes among patients with well-differentiated tumors managed surgically or endoscopically. ConclusionsEsophagectomy was associated with improved survival for cT1bN0 esophageal cancer; however, endoscopic treatment may achieve similar survival in patients with favorable tumor attributes. Further study is warranted.

Epidemiology of Adenosquamous Carcinomas.

Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a fraction of a percent of all solid tumors. The bulk of the literature on ASCs is comprised of case reports and small series, with the general finding that ASCs tend to have worse outcomes than either of their parent histologies. However, there is a lack of pan site-comparative studies in the literature that compare ASC clinicodemographic and survival outcomes with those of conventional adenocarcinomas (ACs) and squamous cell carcinomas (SCCs). In this study, we summarize these outcomes in eight primary sites, comprising 92.7% of all ASC cases diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Lung ASCs comprise 51.5% of all ASC cases, accounting for 1.1% of all lung cancer cases, followed by uterine/cervical cancers at 29.7% of all ASC cases, translating into 1.8% of all cancers in this site. In descending order, the remaining 20% of ASCs arise in pancreatic, oral cavity, biliary, esophageal, colorectal, and gastric sites, comprising between 0.1% and 0.7% of all cancers in these sites. Apart from pancreatic and oral cavity cancers, ASC tumors tended to favor higher rates of regional or distant disease at presentation with poor tumor differentiation compared to either AC or SCC histologies. After multivariable analysis, adjusting for age, sex, detection stage, grade differentiation, surgery, chemotherapy, and radiotherapy, except for oral cavity cancers, ASCs tended to have worse overall survivals compared to ACs (hazard ratios: 1.1 - 1.6) and SCC (1.0 - 1.3), with colorectal ASCs having the worse overall survival compared to colorectal ACs, with a hazard ratio of 1.4 (95% confidence interval: 1.3 - 1.6). Overall, these results suggest that ASC outcomes are site specific, and in general, tend to have worse outcomes than nonvariant ACs and SCCs even after correction for common clinical and epidemiological factors. These cancers have a poorly understood but unique tumor biology that warrants further characterization.