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Tongue cancer is among the most prevalent head and neck cancers and is most commonly treated via surgery. We assessed the articulation differences in patients with early and advanced tongue cancer. The study included 26 postoperative tongue cancer patients. We evaluated articulation based on bilabial, labiodental, apical, posterior, laminal, apical front, and apical back speech sounds. The 26 postoperative tongue cancer patients (24 males, two females) had an average age of 54.3 (range 37–89 old) years. Twelve patients were classified as early T stage (T1/T2), while 14 were classified as advanced T stage (T3/T4). The total articulation score was not significantly related to the T stage but apical sounds were so associated. The total articulation score did not significantly differ between postoperative patients with early and advanced tongue cancer. In subgroup analysis, the apical sound was significantly impaired in postoperative patients with advanced tongue cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are non-melanoma skin cancers (NMSCs) and the most prevalent cancers in the United States. Image-guided superficial radiotherapy (IGSRT) is a relatively new treatment option that uses high-resolution dermal ultrasound integrated with superficial radiotherapy to improve tumor visualization. IGSRT is a clinically equivalent non-surgical alternative to Mohs micrographic surgery at 2 years of follow-up in early-stage NMSC, but larger cohort studies with longer follow-up periods that allow for analysis of patient outcomes by demographic and disease characteristics are needed. Methods: This large, retrospective cohort study was conducted to determine the effect of risk factors (tumor location, tumor stage, and sex) on 2-, 4-, and 6-year freedom from recurrence rates in 19,988 NMSC lesions treated with IGSRT, including lesions with complete treatment courses. Results: Overall freedom from recurrence rates were 99.68% at 2 years, 99.54% at 4 years, and 99.54% at 6 years; rates did not differ significantly by tumor location (head/neck versus other locations, p = 0.9) or sex (male versus female, p = 0.4). In contrast, there was a significant difference in freedom from recurrence rates when analyzed by tumor stage (p = 0.004). Conclusions: There was no significant effect of tumor location or sex on freedom from recurrence in IGSRT-treated NMSC. Although there was a significant difference according to tumor stage, freedom from recurrence rates exceeded 99% at all stages. [ABSTRACT FROM AUTHOR]

Background: Predicting the accurate preoperative staging of bladder cancer (BLCA), which markedly affects treatment decisions and patient outcomes, using traditional clinical parameters is challenging. Nevertheless, emerging studies in radiomics, especially machine learning‐based computed tomography (CT) image‐based radiomics, hold promise in improving stage prediction accuracy in various tumors. However, the comparative performance and clinical utility of models for BLCA are under investigation. Purpose: We aimed to investigate the application value of machine learning‐based CT radiomics in preoperative staging prediction by comparing the performance of clinical, radiomics, and clinical–radiomics combined models. Methods: A retrospective cohort of 105 patients with initial BLCA was randomized into training (70%) and testing (30%) cohorts. Radiomics features were extracted from CT images using the optimal feature filter, followed by the application of the least absolute shrinkage and selection operator algorithm for optimum feature selection. Furthermore, machine learning algorithms were used to establish a radiomics model within the training cohort. Independent risk factors for muscle‐invasive BLCA (MIBC) obtained by multivariate logistic regression (LR) analysis were separately used to construct a clinical model. For a clinical–radiomics fusion model, radiomics features were combined with clinical parameters. Performance was evaluated based on receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and standard performance metrics. Results: Patients exhibited a significantly higher age (p = 0.029), larger tumor size (p = 0.01), and an increased neutrophil‐to‐lymphocyte ratio (NLR; p = 0.045) in the MIBC group than in the NMIBC group. LR analysis revealed age (p = 0.026), tumor size (p = 0.007), and NLR (p = 0.019) as significant predictors for constructing the clinical model. In the testing cohort, the radiomics model, which used an Support Vector Machine classifier, achieved the highest area under the curve (AUC) value of 0.857. The clinical–radiomics model outperformed the remaining two models, with AUC values of 0.958 and 0.893 in the training and testing cohorts, respectively. DeLong's test indicated significant differences between the three models. Calibration curves showed good agreement, and DCA confirmed the superior clinical utility of the clinical–radiomics model. Conclusions: Machine learning‐based CT radiomics combined with clinical parameters was a promising approach in staging BLCA accurately, which outperformed the individual models. Integrating radiomics features with clinical information holds the potential to improve personalized treatment planning and patient outcomes in BLCA. [ABSTRACT FROM AUTHOR]

Macrophages, pivotal components of the immune system, orchestrate host defense mechanisms in humans and mammals. Their polarization into classically activated macrophages (CAMs or M1) and alternatively activated macrophages (AAMs or M2) dictates distinct functional roles in immunity and tissue homeostasis. While the negative regulatory role of CD32b within the FC gamma receptor (FCγR) family is recognized across various immune cell types, its influence on macrophage polarization remains elusive. This study aimed to elucidate the regulatory role of CD32b in macrophage polarization and discern the differential expression markers between the M1 and M2 phenotypes following CD32b siRNA transfection. The results revealed a decrease in the CD32b levels in lipopolysaccharide (LPS)-treated M1 and an increase in interleukin-4 (IL-4)-treated M2 macrophages, as observed in macrophage Raw264.7 cells. Furthermore, CD32b siRNA transfection significantly downregulated the M2 markers (IL-10, VEGF, Arg-1, and STAT6), while upregulating the M1 markers (IL-6, NF-κB, NOS2, and STAT1) in the Raw264.7 cells. Similar findings were recapitulated in macrophage-rich adherent cells isolated from mouse spleens. Additionally, the cytopathological analysis of pleural effusions and ascitic fluids from patients with cancer revealed a positive correlation between advanced tumor stages, metastasis, and elevated CD32b levels. In conclusion, this study highlights the regulatory influence of CD32b in suppressing M1 expression and promoting M2 polarization. Moreover, heightened M2 activation and CD32b levels appear to correlate with tumor progression. A targeted CD32b blockade may serve as a novel therapeutic strategy to inhibit M2 macrophage polarization and is promising for anti-tumor intervention. [ABSTRACT FROM AUTHOR]

Endometrial cancer remains a significant health concern, particularly in developed nations where its prevalence is increasing. Reliable prognostic markers are paramount to enhance disease management and patient outcomes. This study explores the prognostic capabilities of various hematological indices, including the eosinophil-lymphocyte ratio (ELR) and the prognostic nutritional index (PNI), in relation to endometrioid type endometrial cancer (ETEC) staging and grading. We retrospectively analyzed data from ETEC patients, categorizing them by tumor grade and stage, and evaluating their hematological indices from preoperative blood samples. Our results indicated that higher ELR and lower PNI levels correlate with more advanced tumor grades and stages. Additionally, the plateletlymphocyte ratio (PLR) was found to be the most significant marker for staging, with PLT, SII, SIRI, ELR, and PNI also showing significant differences across stages. These findings suggest that hematological indices such as ELR and PNI could be instrumental in predicting tumor grade and stage, offering valuable insights for clinical practice. Future research should focus on prospective studies to confirm these findings and consider the integration of these markers into standard diagnostic protocols. [ABSTRACT FROM AUTHOR]

Abstract Tongue cancer is among the most prevalent head and neck cancers and is most commonly treated via surgery. We assessed the articulation differences in patients with early and advanced tongue cancer. The study included 26 postoperative tongue cancer patients. We evaluated articulation based on bilabial, labiodental, apical, posterior, laminal, apical front, and apical back speech sounds. The 26 postoperative tongue cancer patients (24 males, two females) had an average age of 54.3 (range 37–89 old) years. Twelve patients were classified as early T stage (T1/T2), while 14 were classified as advanced T stage (T3/T4). The total articulation score was not significantly related to the T stage but apical sounds were so associated. The total articulation score did not significantly differ between postoperative patients with early and advanced tongue cancer. In subgroup analysis, the apical sound was significantly impaired in postoperative patients with advanced tongue cancer.

Abstract Background Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. Methods We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. Results Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. Conclusions Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

INTRODUCTION: Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. METHODS: In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. RESULTS: The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score. DISCUSSION: Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems. [ABSTRACT FROM AUTHOR]

Background: New-onset diabetes (NOD) has been identified as a high-risk factor for the early detection of pancreatic ductal adenocarcinoma (PDAC). The role of tumor volume and remnant pancreas volume (RPV) in the progression from normal to NOD in PDAC patients is not fully illustrated yet. Methods: In this cross-sectional study, glycemic metabolism traits of 95 PDAC patients before pancreatic surgery were described and compared with chronic pancreatitis and type 2 diabetes mellitus patients based on the oral glucose tolerance test. The remnant RPV and tumor volume, calculated by three-dimensional reconstruction of radiological images, were included in the ordinal logistic regression models. Results: The prevalence of NOD was high among PDAC patients (38.9%). However, normal glucose tolerance (NGT) or prediabetes mellitus status were present as more than half (24/44) of advanced tumor stage patients. Indexes reflecting beta-cell function but not insulin sensitivity gradually worsened from NGT to NOD patients (all p < 0.05). The remnant pancreas volume (RPV) was identified as a potential protective factor for diabetes secondary to PDAC (odds ratio 0.95, 95% CI [0.92, 0.97], p < 0.001). Conclusions: Reduced RPV causing beta-cell dysfunction might be one of the mechanisms of NOD secondary to PDAC. Subjects with sufficient pancreas volume could not be detected earlier when regarding patients with NOD as the population at risk for PDAC. [ABSTRACT FROM AUTHOR]

Background: Head and neck malignancies pose significant clinical challenges due to their aggressive nature and potential for cervical nodal metastasis. Understanding the correlation between tumor stage and cervical nodal involvement is crucial for prognosis and treatment planning. Methods: This observational study was conducted in the Department of Otorhinolaryngology at a tertiary care hospital over 12 months. Thirty patients aged 12 years and above with biopsy-proven head and neck malignancies who underwent neck dissection were included. Clinical examinations and ultrasound (USG) findings were compared to detect cervical nodal metastasis. Results: Among the 30 participants, the most represented age group was 41-60 years (41.7%), with males constituting 61.1%. Stage III tumors were the most common (36.1%), followed by Stage IV (27.8%). Nodal involvement increased with tumor stage, with Stage IV showing the highest involvement at 44.4%, predominantly in Level II. USG was more sensitive than clinical exams in detecting nodal metastasis. Conclusion: The study highlights the critical correlation between tumor stage and cervical nodal metastatic disease in head and neck malignancies. Early detection, thorough nodal evaluation, and comprehensive treatment strategies are essential to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.

Abstract Background Obesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis. Methods We conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS). Results 22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52–6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06–4.51) and non-obese (HR = 2.11, 95% CI = 1.05–4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS. Conclusions Results suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between the Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors.

Endometrial cancer remains a significant health concern, particularly in developed nations where its prevalence is increasing. Reliable prognostic markers are paramount to enhance disease management and patient outcomes. This study explores the prognostic capabilities of various hematological indices, including the eosinophil-lymphocyte ratio (ELR) and the prognostic nutritional index (PNI), in relation to endometrioid type endometrial cancer (ETEC) staging and grading. We retrospectively analyzed data from ETEC patients, categorizing them by tumor grade and stage, and evaluating their hematological indices from preoperative blood samples. Our results indicated that higher ELR and lower PNI levels correlate with more advanced tumor grades and stages. Additionally, the platelet-lymphocyte ratio (PLR) was found to be the most significant marker for staging, with PLT, SII, SIRI, ELR, and PNI also showing significant differences across stages. These findings suggest that hematological indices such as ELR and PNI could be instrumental in predicting tumor grade and stage, offering valuable insights for clinical practice. Future research should focus on prospective studies to confirm these findings and consider the integration of these markers into standard diagnostic protocols. [Med-Science 2024; 13(3.000): 727-30]

Background: Obesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis. Methods: We conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS). Results: 22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52–6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06–4.51) and non-obese (HR = 2.11, 95% CI = 1.05–4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS. Conclusions: Results suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between the Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC. [ABSTRACT FROM AUTHOR]

Introduction: An increasing number of studies have demonstrated the pivotal role of microbiota changes in the onset, progression, diagnosis, treatment, and prognosis of lung adenocarcinoma (LUAD). However, a comprehensive analysis of intratumoral microbiome variation across distinct LUAD stages has not been performed. The aim of this study was to identify the microbial markers that significantly vary during tumor stage of LUAD. Methods: Here, we used the cancer genome atlas (TCGA) database to comprehensively compare and analyze the differences in microbial composition between 267 patients with early and 224 patients with advanced LUAD. In order to determine the best biomarkers, we used the random forest (RF) model and found that the microbial markers have a certain ability in predicting the stage of LUAD. Results: We found that there were certain differences in the microbiome of patients with LUAD at different stages, especially in the tumor tissues of patients with advanced LUAD, whose co-abundance network was significantly more complex. We also found that five bacterial biomarkers (Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, Loktanella, and Serratia) were correlated with LUAD stage, among which Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, and Serratia were significantly overexpressed in patients with advanced LUAD. In particular, after integrating the biomarkers of mRNA, we achieved an area under the curve (AUC) of 0.70. Discussion: Our study revealed the microbial profile of patients with LUAD and the intrinsic pathogenic mechanism between the microbiome and the disease, and established a multi-omics model to determine LUAD tumor stage. [ABSTRACT FROM AUTHOR]

This is retrospective analysis of prognostic significance of lymph node density in node positive urothelial bladder cancer postneoadjuvant chemotherapy as well as primary surgery. The lymph node ratio has shown to be prognostically significant with the cut off value of 15. This can be used to develop prognostic scoring by further studies. Aim: To validate the role of lymph node density as a prognostic marker in patients undergoing primary surgery and postneoadjuvant therapy in pathological node-positive urothelial bladder carcinoma. Materials and Methods: Retrospective analysis of 503 patients who underwent radical cystectomy from 2006 to 2019 for muscle-invasive urothelial bladder carcinoma, of which 152 patients with pathological node-positive disease were analyzed. Demographic details, pathological findings, treatment details, disease-free, and overall survival were documented. X tile program analysis was used to divide patients with positive lymph nodes into 3 groups: LD1: < = 7, LD2 :> 7 to < 15, LD3: > 15, and the optimal cut-off value obtained was 15%. To evaluate the impact of lymph node ratio, patients with positive lymph nodes into 3 categories for each cut-off point estimation method, the application generates the histogram, Kaplan-Meier plot and calculates hazard ratio, confidence intervals and P -values. Univariate and multivariate cox regression analysis was done with a P -value of < .05, considered significant. Results: One hundred fifty-two patients (30.2%) had pathological nodal metastasis, with 87 of them having perinodal extension. Ninety-six underwent primary surgery, and 56 were postneoadjuvant chemotherapy. The median follow-up was 55.42 months. 68 of the 152 node-positive patients died of the disease. Median number of lymph nodes removed was 17.11. Lymph node density divided into tertiles were LD1 < 7%, LD2 7-< 15%, LD3 > 15% showed 5-year RFS 40.5%,29.3%, 22.6% and 5 year OS was 55.5%, 42.4%,32.1% respectively. Cox regression analysis showed that age less than 55 years, higher tumor stage, lymphovascular invasion, and higher lymph node ratio were significant in univariate and multivariate analysis. The lymph node density cut-off value of 15% was substantial among node-positive patients (P = .027), and subgroup analysis in upfront surgery with the adjuvant treatment group and postneoadjuvant chemotherapy group was also significant (P = .021). Conclusion: Pathological higher T stage, Age < 55 years, Lymphovascular invasion, adjuvant chemotherapy, adjuvant radiation treatment and lymph node density had prognostic significance in both cohorts of patients who underwent upfront surgery and neoadjuvant chemotherapy. Lymph node density cut-off value of < 15% was prognostically significant. [ABSTRACT FROM AUTHOR]

Recently, more and more evidence shows that lipid metabolism disorder has been observed in tumor, which impacts tumor cell proliferation, survival, invasion, metastasis, and response to the tumor microenvironment (TME) and tumor treatment. However, hitherto there has not been sufficient research to demonstrate the role of lipid metabolism in pancreatic cancer. This study contrives to get an insight into the relationship between the characteristics of lipid metabolism and pancreatic cancer. We collected samples of patients with pancreatic cancer from the Gene Expression Omnibus (GEO), the Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the International Cancer Genome Consortium (ICGC) databases. Firstly, we implemented univariate regression analysis to get prognosis-related lipid metabolism genes screened and a construction of protein–protein interaction (PPI) network ensued. Then, contingent on our screening results, we explored the molecular subtypes mediated by lipid metabolism-related genes and the correlated TME cell infiltration. Additionally, we studied the disparately expressed genes among disparate lipid metabolism subtypes and established a scoring model of lipid metabolism-related characteristics using the least absolute shrinkage and selection operator (LASSO) regression analysis. At last, we explored the relationship between the scoring model and disease prognosis, tumor stage, tumor microenvironment, and immunotherapy. Two subtypes, C1 and C2, were identified, and lipid metabolism-related genes were studied. The result indicated that the patients with subtype C2 have a significantly lower survival rate than that of the patients with subtype C1, and we found difference in abundance of different immune-infiltrating cells. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed the association of these differentially expressed genes with functions and pathways related to lipid metabolism. Finally, we established a scoring model of lipid metabolism-related characteristics based on the disparately expressed genes. The results show that our scoring model have a substantial effect on forecasting the prognosis of patients with pancreatic cancer. The lipid metabolism model is an important biomarker of pancreatic cancer. Using the model, the relationship between disease prognosis, molecular subtypes, TME cell infiltration characteristics, and immunotherapy in pancreatic cancer patients could be explored. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a type of neoplasm, developing in the colon or rectum. The exact etiology of CRC is not well known, but the role of genetic, epigenetic, and environmental factors are established in its pathogenesis. Therefore, the aim of this research was to explore the effects of ANRIL polymorphisms on the CRC and its clinical findings. Methods and results: The peripheral blood specimens were collected from 142 CRC patients and 225 controls referred to Milad Hospital, Tehran, Iran. PCR- RFLP method was used to analyze ANRIL rs1333040, rs10757274 rs4977574, and rs1333048 polymorphisms. The ANRIL rs1333040 polymorphism was related to a higher risk of CRC in the co-dominant, dominant, and log-additive models. ANRIL rs10757274, rs4977574, and rs1333048 polymorphisms showed no effect on CRC susceptibility. The CGAA and TGGA haplotypes of ANRIL rs1333040/ rs10757274/ rs4977574/rs1333048 polymorphisms were associated with the higher and the lower risk of CRC respectively. The rs1333040 polymorphism was associated with higher TNM stages (III and IV). The frequency of ANRIL rs10757274 polymorphism was lower in CRC patients over 50 years of age only in the dominant model. In addition, the rs10757274 was associated with well differentiation in CRC patients. Conclusion: The ANRIL rs1333040 polymorphism was associated with a higher risk of CRC and higher TNM stages. ANRIL rs10757274 polymorphism was associated with the well-differentiated tumor in CRC. [ABSTRACT FROM AUTHOR]

Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients. [ABSTRACT FROM AUTHOR]

Background: T cell exhaustion and activation markers are helpful in determining the therapies and predicting the overall survival in pancreatic cancer (PC) patients. Purpose: In this systematic review, we have addressed two questions, how do these markers differ in their expression levels in PC patients and healthy individual and correlating the expression level of these markers with the cancer stage. Methods: The systematic review was registered with Prospective Register of Systematic Reviews (PROSPERO) with registration number "CRD42022246780." All the included articles were obtained from three databases, PubMed, MEDLINE, and Cochrane, published from January 2010 to 26th May 2022. Two independent reviewers followed the PRISM protocol and reviewed and extracted data from the included articles. Results: PD-1 and CTLA-4 were the most studied markers in this field. A clear elevation in the expression of PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT was found in most of the studies. CD69, CD25, and HLA-DR expression was found to be upregulated after chemotherapy and immunotherapy. CD25 was the only marker analyzed against cancer progression, in a single study. No study compared the expression of exhaustion and activation markers (except CD69) with the cancer progression of the tumor stage. Conclusion: Since the exhaustion markers are upregulated in patients, single or multiple markers can be targeted in immunotherapies. Knowledge of the dynamics of these markers at various cancer stages will help in determining the right immunotherapy for pancreatic cancer patients. Stage-wise comparison could also be made possible by developing in vitro models. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential application of radiomics in predicting Tumor-Node-Metastasis (TNM) stage in patients with resectable esophageal squamous cell carcinoma (ESCC). Methods: This retrospective study included 122 consecutive patients (mean age, 57 years; 27 women). Corresponding tumor of interest was identified on axial arterial-phase CT images with manual annotation. Radiomics features were extracted from intra- and peritumoral regions. Features were pruned to train LASSO regression model with 93 patients to construct a radiomics signature, whose performance was validated in a test set of 29 patients. Prognostic value of radiomics-predicted TNM stage was estimated by survival analysis in the entire cohort. Results: The radiomics signature incorporating one intratumoral and four peritumoral features was significantly associated with TNM stage. This signature discriminated tumor stage with an area under curve (AUC) of 0.823 in the training set, with similar performance in the test set (AUC 0.813). Recurrence-free survival (RFS) was significantly different between different radiomics-predicted TNM stage groups (Low-risk vs high-risk, log-rank P = 0.004). Univariate and multivariate Cox regression analyses revealed that radiomics-predicted TNM stage was an independent preoperative factor for RFS. Conclusions: The proposed radiomics signature combing intratumoral and peritumoral features was predictive of TNM stage and associated with prognostication in ESCC. [ABSTRACT FROM AUTHOR]

Background: To evaluate two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) radiomics analysis for the T stage of esophageal squamous cell carcinoma (ESCC). Methods: 398 patients with pathologically confirmed ESCC were divided into training and testing sets. All patients underwent chest CT scans preoperatively. For each tumor, based on CT images, a 2D region of interest (ROI) was outlined on the largest cross-sectional area, and a 3D ROI was outlined layer by layer on each section of the tumor. The radiomics platform was used for feature extraction. For feature selection, stepwise logistic regression was used. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the 2D radiomics model versus the 3D radiomics model. The differences were compared using the DeLong test. The value of the clinical utility of the two radiomics models was evaluated. Results: 1595 radiomics features were extracted. After screening, two radiomics models were constructed. In the training set, the difference between the area under the curve (AUC) of the 2D radiomics model (AUC = 0.831) and the 3D radiomics model (AUC = 0.830) was not statistically significant (p = 0.973). In the testing set, the difference between the AUC of the 2D radiomics model (AUC = 0.807) and the 3D radiomics model (AUC = 0.797) was also not statistically significant (p = 0.748). A 2D model was equally useful as a 3D model in clinical situations. Conclusion: The performance of 2D radiomics model is comparable to that of 3D radiomics model in distinguishing between the T1-2 and T3-4 stages of ESCC. In addition, 2D radiomics model may be a more feasible option due to the shorter time required for segmenting the ROI. [ABSTRACT FROM AUTHOR]

Introduction: Cancer biomarkers are substances or processes highly associated with the presence and progression of cancer, which are applicable for cancer screening, progression surveillance, and prognosis prediction in clinical practice. In our previous studies, we discovered that cancer cells upregulate inositol 1,4,5-triphosphate receptor-interacting protein-like 1 (ITPRIPL1), a natural CD3 ligand, to evade immune surveillance and promote tumor growth. We also developed a monoclonal ITPRIPL1 antibody with high sensitivity and specificity. Here, we explored the application of anti-ITPRIPL1 antibody for auxiliary diagnosis of non-small cell lung cancer (NSCLC). Methods: NSCLC patient tissue samples (n = 75) were collected and stained by antiITPRIPL1 or anti-CD8 antibodies. After excluding the flaked samples (n = 15), we evaluated the expression by intensity (0-3) and extent (0-100%) of staining to generate an h-score for each sample. The expression status was classified into negative (h-score < 20), low-positive (20-99), and high-positive (≥ 100). We compared the hscores between the solid cancer tissue and stroma and analyzed the correlation between the h-scores of the ITPRIPL1 and CD8 expression in situ in adjacent tissue slices. Results: The data suggested ITPRIPL1 is widely overexpressed in NSCLC and positively correlates with tumor stages. We also found that ITPRIPL1 expression is negatively correlated with CD8 staining, which demonstrates that ITPRIPL1 overexpression is indicative of poorer immune infiltration and clinical prognosis. Therefore, we set 50 as the cutoff point of ITPRIPL1 expression H scores to differentiate normal and lung cancer tissues, which is of an excellent sensitivity and specificity score (100% within our sample collection). Discussion: These results highlight the potential of ITPRIPL1 as a proteomic immunohistochemical NSCLC biomarker with possible advantages over the existing NSCLC biomarkers, and the ITPRIPL1 antibody can be applied for accurate diagnosis and prognosis prediction. [ABSTRACT FROM AUTHOR]

Background: New-onset diabetes (NOD) has been identified as a high-risk factor for the early detection of pancreatic ductal adenocarcinoma (PDAC). The role of tumor volume and remnant pancreas volume (RPV) in the progression from normal to NOD in PDAC patients is not fully illustrated yet. Methods: In this cross-sectional study, glycemic metabolism traits of 95 PDAC patients before pancreatic surgery were described and compared with chronic pancreatitis and type 2 diabetes mellitus patients based on the oral glucose tolerance test. The remnant RPV and tumor volume, calculated by three-dimensional reconstruction of radiological images, were included in the ordinal logistic regression models. Results: The prevalence of NOD was high among PDAC patients (38.9%). However, normal glucose tolerance (NGT) or prediabetes mellitus status were present as more than half (24/44) of advanced tumor stage patients. Indexes reflecting beta-cell function but not insulin sensitivity gradually worsened from NGT to NOD patients (all p < 0.05). The remnant pancreas volume (RPV) was identified as a potential protective factor for diabetes secondary to PDAC (odds ratio 0.95, 95% CI [0.92, 0.97], p < 0.001). Conclusions: Reduced RPV causing beta-cell dysfunction might be one of the mechanisms of NOD secondary to PDAC. Subjects with sufficient pancreas volume could not be detected earlier when regarding patients with NOD as the population at risk for PDAC.

Abstract Background Current guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous. Methods This single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups. Results After median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087–1.531) and DFS (aHR, 1.397; 95% CI, 1.207–1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211–1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively). Conclusion PNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.

Introduction: Cancer biomarkers are substances or processes highly associated with the presence and progression of cancer, which are applicable for cancer screening, progression surveillance, and prognosis prediction in clinical practice. In our previous studies, we discovered that cancer cells upregulate inositol 1,4,5-triphosphate receptor-interacting protein-like 1 (ITPRIPL1), a natural CD3 ligand, to evade immune surveillance and promote tumor growth. We also developed a monoclonal ITPRIPL1 antibody with high sensitivity and specificity. Here, we explored the application of anti-ITPRIPL1 antibody for auxiliary diagnosis of non-small cell lung cancer (NSCLC).Methods: NSCLC patient tissue samples (n = 75) were collected and stained by anti-ITPRIPL1 or anti-CD8 antibodies. After excluding the flaked samples (n = 15), we evaluated the expression by intensity (0-3) and extent (0-100%) of staining to generate an h-score for each sample. The expression status was classified into negative (h-score < 20), low-positive (20-99), and high-positive (≥ 100). We compared the h-scores between the solid cancer tissue and stroma and analyzed the correlation between the h-scores of the ITPRIPL1 and CD8 expression in situ in adjacent tissue slices.Results: The data suggested ITPRIPL1 is widely overexpressed in NSCLC and positively correlates with tumor stages. We also found that ITPRIPL1 expression is negatively correlated with CD8 staining, which demonstrates that ITPRIPL1 overexpression is indicative of poorer immune infiltration and clinical prognosis. Therefore, we set 50 as the cutoff point of ITPRIPL1 expression H scores to differentiate normal and lung cancer tissues, which is of an excellent sensitivity and specificity score (100% within our sample collection).Discussion: These results highlight the potential of ITPRIPL1 as a proteomic immunohistochemical NSCLC biomarker with possible advantages over the existing NSCLC biomarkers, and the ITPRIPL1 antibody can be applied for accurate diagnosis and prognosis prediction.

Objectives: Nrf2/BACH1/HO-1 proteins have been implicated in the development and progression of tumors. However, their clinical relevance in breast cancer remains unclear and understudied. This study evaluated Nrf2/BACH1/HO-1 protein expression and its relationship with age, tumor grade, tumor stage, TNM, ER, PR, HER2, and histologic type. Methods: 114 female breast cancer and 30 noncancerous tissues were evaluated for Nrf2/BACH1/HO-1 protein expression using immunohistochemistry and Western blot. The relationships between the expression and clinicopathologic factors were assessed using the χ2 test. Results: 74% of the cancerous samples had high Nrf2 protein expression, and 26% of them had low Nrf2 protein expression. Regarding the non-cancer samples, 43% had high Nrf2 protein expression and 57% had low Nrf2 protein expression (p < 0.002). 39% of the cancerous samples had high BACH1 protein expression, and 61% had low BACH1 protein expression. For the non-cancer samples, 80% had high BACH1 protein expression and 20% had low BACH1 protein expression (p < 0.031). 67% of the cancerous samples had high HO-1 protein expression, and 33% had low HO-1 protein expression. However, for the non-cancer samples, 17% of them had high HO-1 protein expression and 83% had low HO-1 protein expression (p < 0.001). The expression of Nrf2 and HO-1 significantly correlated with tumor grade, while BACH1 was significantly associated with tumor stage (p < 0.05). Conclusion: Nrf2, BACH1, and HO-1 could be explored as a biomarker for cancer stage, progression, and prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer behaves differently according to the primary tumor location. Medially located breast tumors were thought to have a worse prognosis than laterally located breast tumors. Studies showed that central tumors tend to present at a relatively more advanced stage with more features of a locally advanced disease. Lateral, medial, and central breast tumors are not well studied in Bahrain and worldwide; therefore, we aimed to clarify the incidence & clinicopathological characteristics of each and to explore the impact of primary tumor location on the prognosis. Materials and Methods: This is a cross-sectional, retrospective review involving 233 consecutive breast cancer Bahraini female patients that were divided into 3 groups in relation to primary tumor location: lateral, medial, and central. Pertinent clinicopathological variables were analyzed in relation to the primary tumor localization in the breast. Results: Lateral breast cancer patients (N=133, 57.1%), medial breast cancer patients (N=64, 27.5%), and central breast cancer patients (N=36, 15.4%). Chi-square test showed a significant association between central tumor location and tumor size (p-value=0.008), lymph node status (p-value=0.010), and tumor stage (p-value=<0.001). Conclusion: This is the first study from Bahrain regarding the possible impact of primary tumor location on the outcome of breast cancer. Although the lateral breast tumors have the highest incidence, the central tumors were more likely to present with a locally advanced disease, larger than 5 cm tumor size, and axillary lymph node metastasis. They also tended to have a higher ratio of lymphovascular invasion and HER2 over expression. Multicenter meta-analysis is needed to evaluate the real impact of primary tumor location and internal mammary lymph node evaluation on the outcome of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Multifocal (MF) and multicentric (MC) breast cancer cases have been increasingly diagnosed owing to the extensive use of improved preoperative breast imaging. The current tumor‐node‐metastasis staging system uses the dimension of the largest tumor and recommends reporting the pathological features of the largest tumor in MF/MC breast cancers. Aim This study aimed to explore whether the largest or aggregate dimensions of MF and MC breast cancers can better predict tumor behavior. We also attempted to study the histological and biological heterogeneities of separate foci in MF and MC breast cancers to determine whether it was necessary to examine each lesion. Methods We retrospectively analyzed 121 patients with MF/MC (103 with MF and 18 with MC) breast cancers and 484 patients with unifocal breast cancer who were treated at the First Affiliated Hospital of Nanjing Medical University. Two methods were used to record the T stage (using the dimensions of the largest lesion and aggregate dimensions of all lesions). The histological grade, immunohistochemical parameters, and molecular subtypes of the largest lesion and other lesions in MF/MC breast cancers were studied to assess intertumoral heterogeneity. Results The use of aggregate dimensions upstaged 63 patients with MF/MC breast cancers to a more advanced stage and removed the independent effect of cancer multiplicity on lymph node positivity compared with the use of the largest dimension. Mismatches were found in the pathological type (9.9%), histological grade (4.1%), and molecular subtype (8.3%) among different foci. Conclusion The tendency of MF/MC breast tumors to metastasize may be related to tumor load, which can be better predicted by the aggregate dimensions of all foci. The use of the current staging systems may require further evaluation and modification. Intertumoral heterogeneity indicates the necessity for pathological and immunohistochemical assessments of each lesion in patients with MF/MC breast cancers.

Abstract Tumor deposits (TDs) are discontinuous tumor spread in the mesocolon/mesorectum which is found in approximately 20% of colorectal cancer (CRC) and negatively affects survival. We have a history of repeated revisions on TD definition and categorization in the tumor‐node‐metastasis (TNM) system leading to stage migration. Since 1997, TDs have been categorized as T or N factors depending on their size (TNM5) or contour (TNM6). In 2009, TNM7 provided the category of N1c for TDs in a case without positive lymph nodes (LNs), which is also used in TNM8. However, increasing evidence suggests that these revisions are suboptimal and only “partially” successful. Specifically, the N1c rule is certainly useful for oncologists who are having difficulty with TDs in a case with no positive LNs. However, it has failed to maximize the value of the TNM system because of the underused prognostic information of individual TDs. Recently, the potential value of an alternative staging method has been highlighted in several studies using the “counting method.” For this method, all nodular type TDs are individually counted together with positive LNs to derive the final pN, yielding a prognostic and diagnostic value that is superior to existing TNM systems. The TNM system has long stuck to the origin of TDs in providing its categorization, but it is time to make way for alternative options and initiate an international discussion on optimal treatment of TDs in tumor staging; otherwise, a proportion of patients end up missing an opportunity to receive the optimal adjuvant treatment.

ObjectivesTumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival.Materials and methodsRetrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman's coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant.ResultsAs a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P

Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients.

Objectives: To evaluate the clinical utility of voided urine fluorescence in situ hybridization (FISH) for predicting the pathology of preoperative "low-risk" upper tract urothelial carcinoma (UTUC). Methods: Information of patients preoperatively diagnosed with "low-risk" UTUC receiving radical nephroureterectomy (RNU) between May 2014 and October 2019 were retrospectively collected. All of the patients accepted the FISH test and then were divided into two groups according to the results of FISH. The diagnostic value of FISH was assessed through the receiver operating characteristics (ROC) curve and area under the curve. Logistic regression analysis was applied to examine FISH as a predictive factor of tumor final stage and grade of preoperative "low-risk" UTUC. Results: In total, 129 patients were included. Of them, 70 (54.2%) were marked with positive FISH result. The difference at final pathology in tumor stage and tumor grade between these two groups of FISH (-) and FISH (+) had significantly statistical significance (p<0.001). Regarding to the tumor stage at final pathology, the sensitivity, specificity, positive predictive value and negative predictive value of FISH were 70.7 (58.9-80.3)68.5 (54.3-80.1)75.7 (63.7-84.8) and 62.7 (49.1-74.7), respectively. Regarding to the tumor grade at final pathology, the sensitivity, specificity, positive predictive value and negative predictive value of FISH were 64.7 (53.5-74.6), 65.9 (50.0-79.1), 78.6 (66.8-87.1) and 49.1 (36.5-62.3), respectively. The results of logistic regression analysis indicated that FISH could predict the pathologic characteristics of preoperative "low-risk" UTUC independently. Conclusions: FISH was qualified with relatively high diagnostic estimates for predicting tumor stage and grade of preoperative "low-risk" UTUC, and could be an independent predictive factor in clinical practice. For preoperative "low-risk" UTUC patients but with positive FISH result, choosing nephron-sparing surgery may require special caution. [ABSTRACT FROM AUTHOR]

Objective: to find an association between the serum CA-125 level and the histopathological type of ovarian tumor. Study Design: Cross-sectional study. Place and Duration of Study: Medical Oncology, Jinnah postgraduate Medical Center, Karachi Pakistan from Jan 2018 to Dec 2019. Methodology: This study included 107 patients presenting with epithelial ovarian cancer. In each case, histological type, pathological stage, degree of differentiation and serum CA-125 was evaluated. The association between preoperative CA-125 and histopathological type of tumor were evaluated. Result: About 107 ovarian cancer patients were included. The mean age in our study was 50.80±10.16 years. Raised CA-125 level was found in most of the patients with serous histology 46(56.1%). Conclusion: Serum level CA-125 elevated in most patients with serous histology. A statistically non-significant association was found between raise CA-125 levels and histological types of ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors and 149 long-term survivors and compared them to 352 intermediate-term survivors of pancreatic ductal adenocarcinoma (PDAC) who received NAT and pancreatoduodenectomy. We found that lymph node stage (ypN) was an independent predictor of both short-term and long-term survivors. In addition, tumor differentiation was an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data. Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15–60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data. [ABSTRACT FROM AUTHOR]

Aim This study characterizes Colorectal Cancer (CRC) incidence in the University Hospital Ramon and Cajal, Madrid, and analyzes variations over time. It establishes risk groups, aiming to discover whether diagnosis can be determined in less advanced stages of disease. Method Evolutionary epidemiological study of genetic and environmental factors contributing to the development of CRC in this district that enables the comparison of two cohorts of patients separated by 37 years: G1 (patients of current group) and G2 (patients of historical group). The main risk variables gleaned retrospectively were analyzed and the statistical association between cohorts was determined. Results The mean age of patients increased significantly from 64 to 71 along with the incidence of ascending colon cancer. G1 scored higher than G2 for: the incidence of colon cancer in men, detection of adenomatous polyps (48.1%), percentage of resectability with curative intent (80.4%), and Dukes A stage (34.1%) (p < 0.001). Conclusion Biological aspects of CRC have been compared against its profile three decades earlier. We can confirm the existence of concrete changes in the manifestation and staging at the time of diagnosis or following earlier treatment.

Simple Summary: This study is to examine the clinical and pathologic characteristics and survival in patients who received neoadjuvant FOLFINOX or neoadjuvant gemcitabine/nab-paclitaxel (GemNP) followed by surgery with curative intent. Our study demonstrated that neoadjuvant FOLFIRINOX treatment is associated with younger age, higher rate of borderline resectable and locally advance disease, higher rate of radiation, lower ypN stage, and higher frequency of complete or near complete pathologic response compared to the GemNP group, but no significant differences in either disease-free survival or overall survival between these two treatment groups. We also demonstrated that multiple pathologic factors, including tumor response group, ypT, ypN, LVI, PNI, and resection margin status, were significant prognostic factors for survival in this group of PDAC patients. In addition, our findings suggest that the tumor size of 1.0 cm is a better cutoff for ypT2 in PDAC patients who received neoadjuvant therapy. Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies. [ABSTRACT FROM AUTHOR]

Background: Multifocal (MF) and multicentric (MC) breast cancer cases have been increasingly diagnosed owing to the extensive use of improved preoperative breast imaging. The current tumor‐node‐metastasis staging system uses the dimension of the largest tumor and recommends reporting the pathological features of the largest tumor in MF/MC breast cancers. Aim: This study aimed to explore whether the largest or aggregate dimensions of MF and MC breast cancers can better predict tumor behavior. We also attempted to study the histological and biological heterogeneities of separate foci in MF and MC breast cancers to determine whether it was necessary to examine each lesion. Methods: We retrospectively analyzed 121 patients with MF/MC (103 with MF and 18 with MC) breast cancers and 484 patients with unifocal breast cancer who were treated at the First Affiliated Hospital of Nanjing Medical University. Two methods were used to record the T stage (using the dimensions of the largest lesion and aggregate dimensions of all lesions). The histological grade, immunohistochemical parameters, and molecular subtypes of the largest lesion and other lesions in MF/MC breast cancers were studied to assess intertumoral heterogeneity. Results: The use of aggregate dimensions upstaged 63 patients with MF/MC breast cancers to a more advanced stage and removed the independent effect of cancer multiplicity on lymph node positivity compared with the use of the largest dimension. Mismatches were found in the pathological type (9.9%), histological grade (4.1%), and molecular subtype (8.3%) among different foci. Conclusion: The tendency of MF/MC breast tumors to metastasize may be related to tumor load, which can be better predicted by the aggregate dimensions of all foci. The use of the current staging systems may require further evaluation and modification. Intertumoral heterogeneity indicates the necessity for pathological and immunohistochemical assessments of each lesion in patients with MF/MC breast cancers. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we examined the natural course of untreated hepatocellular carcinoma (HCC) and identified predictors of survival in an area where hepatitis B is the predominant cause of HCC. Methods: We identified 1,045 patients with HCC who did not receive HCC treatment and were registered in the Korean Primary Liver Cancer Registry between 2008 and 2014, and were followed-up up to December 2018. Thereafter, we analyzed the clinical characteristics of patients who survived for <12 or =12 months. A Cox proportional regression model was used to identify the variables associated with patient survival. Results and discussion: Themean age of the untreated patients at HCC diagnosis was 59.6 years, and 52.1% of patients had hepatitis B. Most untreated patients (94.2%) died during the observation period. The median survival times for each Barcelona Clinic Liver Cancer (BCLC) stage were as follows: 31.0months for stage 0/A (n = 123), 10.0 months for stage B (n = 96), 3.0 months for stage C (n = 599), and 1.0 month for stage D (n = 227). Multivariate Cox regression analysis demonstrated that BCLC stage D (hazard ratio, 4.282; P < 0.001), model for end-stage liver disease (MELD) score =10 (HR, 1.484; P < 0.001), and serumalphafetoprotein (AFP) level =1,000 ng/mL (HR, 1.506; P < 0.001) were associated with poor survival outcomes in patients with untreated HCC. In untreated patients with HCC, advanced stage BCLC, serum AFP level =1,000 ng/mL, and MELD score =10 were significantly associated with overall survival. [ABSTRACT FROM AUTHOR]

Simple Summary: LL-37 contributes the vertical invasion of tumor cells in melanoma. Indeed, the ratio of LL-37-expressing cells correlated positively to T stage severity. Moreover, LL-37 induced pro-angiogenic factors in both human and mouse systems. Our results suggested that LL-37 stimulates both tumor cells and macrophages to promote melanoma invasion by the induction of pro-angiogenic factors. LL-37 can stimulate various skin-resident cells to contribute to tumor development. Since tumor (T) stage is determined by the vertical invasion of tumor cells in melanoma, we hypothesized that the LL-37 expression level is correlated with the T stage in melanoma patients. Immunohistochemical staining of LL-37 was performed in each stage of melanoma (Tis-T4), suggesting the ratio of LL-37-expressing cells correlate positively to T stage severity. Next, to examine pro-angiogenetic factors induced by LL-37 stimulation, the B16F10 melanoma model was used. Intra-tumorally administered CRAMP, the mouse ortologe of LL-37, significantly increased the mRNA expression of CXCL5, IL23A, MMP1a, and MMP9 in B16F10 melanoma. To confirm the induction of pro-angiogenic factors, A375 human melanoma cells were stimulated by LL-37 in vitro. The mRNA expression of CXCL5, IL23A, and MMP9, but not MMP1, were significantly increased by LL-37 stimulation. Moreover, LL-37-stimulated A375 culture supernatant promoted tube networks, suggesting that these tumor-derived factors promote the pro-angiogenic effect on tumor development. In contrast to melanoma cell lines, M2 macrophages stimulated by LL-37 in vitro significantly increased their expression and secretion of MMP-1, but not MMP-9 expression. Collectively, these results suggest that LL-37 stimulates both tumor cells and macrophages to promote melanoma invasion by the induction of pro-angiogenic factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Most patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed in the advanced stages of the disease. The tumor stage is one of the most important prognostic factors for patients with this type of cancer. However, it is unknown whether the dietary pattern is related to prognostic factors in cancer, such as the tumor stage and cell differentiation. The aim of our cross-sectional study was to investigate the association between dietary patterns, tumor staging, and the degree of cellular differentiation in patients newly diagnosed with HNSCC. We found that a greater adherence to a dietary pattern consisting of processed foods was associated with advanced staging. This information contributes to the construction of nutritional guidance for reducing the risk of HNSCC. Purpose: This study aimed to assess the association between dietary patterns and tumor staging and the degree of cell differentiation in patients with head and neck squamous cell carcinoma (HNSCC). Methods: This cross-sectional study included 136 individuals newly diagnosed with different stages of HNSCC, aged 20- to 80 years-old. Dietary patterns were determined by principal component analysis (PCA), using data collected from a food frequency questionnaire (FFQ). Anthropometric, lifestyle, and clinicopathological data were collected from patients' medical records. Disease staging was categorized as initial stage (stages I and II), intermediary (stage III), and advanced (stage IV). Cell differentiation was categorized as poor, moderate, or well-differentiated. The association of dietary patterns with tumor staging and cell differentiation was evaluated using multinomial logistic regression models and adjusted for potential confounders. Results: Three dietary patterns, "healthy," "processed," and "mixed," were identified. The "processed" dietary pattern was associated with intermediary (odds ratio (OR) 2.47; 95% confidence interval (CI) 1.43–4.26; p = 0.001) and advanced (OR 1.78; 95% CI 1.12–2.84; p = 0.015) staging. No association was found between dietary patterns and cell differentiation. Conclusion: A high adherence to dietary patterns based on processed foods is associated with advanced tumor staging in patients newly diagnosed with HNSCC. [ABSTRACT FROM AUTHOR]

Tumor deposits (TDs) are discontinuous tumor spread in the mesocolon/mesorectum which is found in approximately 20% of colorectal cancer (CRC) and negatively affects survival. We have a history of repeated revisions on TD definition and categorization in the tumor‐node‐metastasis (TNM) system leading to stage migration. Since 1997, TDs have been categorized as T or N factors depending on their size (TNM5) or contour (TNM6). In 2009, TNM7 provided the category of N1c for TDs in a case without positive lymph nodes (LNs), which is also used in TNM8. However, increasing evidence suggests that these revisions are suboptimal and only "partially" successful. Specifically, the N1c rule is certainly useful for oncologists who are having difficulty with TDs in a case with no positive LNs. However, it has failed to maximize the value of the TNM system because of the underused prognostic information of individual TDs. Recently, the potential value of an alternative staging method has been highlighted in several studies using the "counting method." For this method, all nodular type TDs are individually counted together with positive LNs to derive the final pN, yielding a prognostic and diagnostic value that is superior to existing TNM systems. The TNM system has long stuck to the origin of TDs in providing its categorization, but it is time to make way for alternative options and initiate an international discussion on optimal treatment of TDs in tumor staging; otherwise, a proportion of patients end up missing an opportunity to receive the optimal adjuvant treatment. [ABSTRACT FROM AUTHOR]

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Breast cancer (BC) is the most common type of cancer among women in almost all countries worldwide and is one of the oncological pathologies for which is indicated fertility preservation, a type of procedure used to help keep a person's ability to have children. Follicular fluid (FF) is a major component of oocyte microenvironment, which is involved in oocyte growth, follicular maturation, and in communication between germ and somatic cells; furthermore, it accumulates all metabolites during oocytes growth. To obtain information about changes on fertility due to cancer, we aimed at investigating potential biomarkers to discriminate between FF samples obtained from 16 BC patients and 10 healthy women undergoing in vitro fertilization treatments. An NMR-based metabolomics approach was performed to investigate the FF metabolic profiles; ELISA and western blotting assays were used to investigate protein markers of oxidative and inflammatory stress, which are processes closely related to cancer. Our results seem to suggest that FFs of BC women display some significant metabolic alterations in comparison to healthy controls, and these variations are also related with tumor staging. [ABSTRACT FROM AUTHOR]

BackgroundPrevious studies focused on the impact of cardiovascular diseases (CVD) risk factors in breast cancer patients with chemotherapy (CT) or radiotherapy (RT). This study aimed to identify the impact of tumor characteristics on CVD death in these patients.MethodsData of female breast cancer patients with CT or RT between 2004 and 2016 were included. The risk factors of CVD death were identified using Cox regression analyses. A nomogram was constructed to evaluate the predicted value of tumor characteristics, and then validated by the concordance indexes (C-index) and calibration curves.ResultA total of 28,539 patients were included with an average follow-up of 6.1 years. Tumor size > 45 mm (adjusted HR = 1.431, 95% CI = 1.116–1.836, P = 0.005), regional (adjusted HR = 1.278, 95% CI = 1.048–1.560, P = 0.015) and distant stage (adjusted HR = 2.240, 95% CI = 1.444–3.474, P

Gasdermin proteins (GSDMs) form pores in cell membranes upon various stimuli, leading to the release of certain proinflammatory molecules such as IL-1β and IL-18, and this ultimately results in pyroptotic cell death. NINJ1 (Ninjurin 1) has recently been identified as a cell membrane protein responsible for the final complete plasma membrane rupture following lytic cell death mechanisms including pyroptosis, causing the release of relatively larger molecules such as HMGB1 and LDH. In this study, we reported the presence of higher GSDMD and lower GSDME protein levels in ovarian tumors compared to surrounding non-malignant stroma in the tumor microenvironment. GSDME protein levels are also lower in the tumors of the omentum compared to adjacent stromal cells. We found that NINJ1 expression decreases from early to late stage in serous ovarian cancer, and the percentage of NINJ1 copy number loss events is the highest in ovarian cancer among other cancers. Moreover, we showed that low expression of NINJ1 is associated with shorter overall survival of patients with ovarian cancer. In support of the findings showing that low NINJ1 expression contributes to worse prognosis in this most lethal gynecological malignancy, NINJ1 expression was found to be lower in cisplatin-resistant ovarian cancer cells compared to cisplatin-sensitive counterparts in vitro. We suggest that the members of gasdermin family might have distinct functions in serous ovarian cancer, and low levels of NINJ1 might contribute, at least in part, to the progression and poorer prognosis of ovarian cancer. A complete picture of how pyroptosis and subsequent plasma membrane rupture are involved in ovarian cancer will be of high importance in order to identify actionable therapeutic vulnerabilities within this newly identified group of proteins. [ABSTRACT FROM AUTHOR]