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Epidemiological evidence on myoepithelial carcinoma is rare. This study aimed to investigate the effect of tumor primary site and treatment modality on survival in patients with head and neck myoepithelial carcinoma. Data on adult patients diagnosed with head and neck myoepithelial carcinoma between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Uni- and multivariable Cox proportional hazard models were utilized to evaluate the effects of different tumor primary sites and treatment modalities on overall survival (OS) and cancer-specific survival (CSS), and expressed as hazard ratio (HR) and 95% confidence interval (CI). A total of 415 patients were enrolled. No significant differences in OS and CSS were found between different tumor primary sites (P > 0.05). Compared with partial excision, patients with total excision (HR = 1.65, 95%CI: 1.12–2.42) (partial or total removal of the organ in which the tumor is located and complete removal of the tumor) or no surgery (HR = 3.52, 95%CI: 2.05–6.03) had worse OS. Compared with surgery only, patients with radiotherapy only had poorer OS (HR = 4.69, 95%CI: 2.32–9.46) and CSS (HR = 6.72, 95%CI: 2.59–17.46), while no significant differences in OS (P = 0.120) and CSS (P = 0.847) were found among patients who received surgery combined with radiotherapy. In patients with AJCC III/IV, patients with radiotherapy only (HR = 4.51, 95%CI: 1.61–12.62) had poorer OS compared to those with surgery only, whereas patients who received surgery combined with radiotherapy had better OS (HR = 0.50, 95%CI: 0.29–0.89). The tumor primary site may not affect the prognosis of patients with myoepithelial carcinoma, while the effect of treatment modality on prognosis is related to the primary site and stage of the tumor. • Primary site may not affect the survival of patients with myoepithelial carcinoma. • Total organ excision may be related to worse OS/CSS compared to partial excision. • Surgery plus radiotherapy did not show better survival compared to surgery alone. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F‐FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). Methods: This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F‐FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index‐1 (HI‐1; standard deviation [SD] divided by SUVmean) and heterogeneity index‐2 (HI‐2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. Results: The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI‐1 were significant prognostic factors for progression‐free survival (PFS), while MTV, HI‐2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI‐1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI‐1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI‐1 ≥ 0.16 compared to those with stages I and II and HI‐1 < 0.16 (log‐rank p < 0.001). Conclusion: HI‐1 and TNM stage were independent prognostic factors for progression‐free survival in TETs. HI‐1 generated from baseline 18F‐FDG PET/CT might be promising to identify patients with poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the potential role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [18F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUVmax, MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUVmax, TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUVmax, MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [18F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholesterol and cholesterol derivatives accumulate in prostate cancer cells. Epidemiologic studies about diet and/or treatment with cholesterol-lowering drugs indicate that this metabolite plays a role in cancer progression, but they do not discriminate its possible role in cancer incidence. The goal of this study is so to determine whether cholesterol availability impacts tumor formation itself. Using a drosophila model specifically dedicated to the study of early epithelial tumorigenesis, we find that basal extrusion, a critical step of tumor formation, directly depends on cholesterol availability through dietary intake, and on cholesterol metabolization by the tumor cells. As we find that many genes related to cholesterol homeostasis and metabolism are ill-expressed in primary prostate cancer samples, this work indicates that cholesterol levels and metabolism could play a crucial role in the early phases of prostate cancer as well. Epidemiological studies point to cholesterol as a possible key factor for both prostate cancer incidence and progression. It could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, it remains unknown whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis. Oncogene clonal induction in the Drosophila melanogaster accessory gland allows us to reproduce tumorigenesis from initiation to early progression, where tumor cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, a high-cholesterol diet has a limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport, or metabolic response impairs the formation of such tumors. Furthermore, in this context, a high-cholesterol diet suppresses this impairment. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Taken together, these results reveal that during early tumorigenesis, tumor cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Hence, these results suggest the mechanism by which a reduction in dietary cholesterol could lower the risk and slow down the progression of prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic inflammation is one of the major risk factors for colorectal cancer development. This study aims to determine the effect of genetic mutations on inflammation-induced colon tumor cell heterogeneity and differentiation. Using single-cell approaches, we found that the addition of BRAFV600E to Apc mutant mice (BLM) increased colon epithelial tumor differentiation. Additionally, we found that BLM epithelial tumors had increased expression of revival colon stem cell (RevCSC) markers and reduced WNT signaling compared to Apc mutant epithelial tumors (Min). In contrast, the loss of Msh2 in Min mice (MSH2KO) increased epithelial tumor stem cell populations with increased WNT signaling compared to Min epithelial tumor. We also identified additional potential regulators of BLM epithelial tumor differentiation such as CDX2 and NDRG1. Genetic mutations and chronic inflammation of the colon contribute to the development of colorectal cancer (CRC). Using a murine model of inflammation-induced colon tumorigenesis, we determined how genetic mutations alter colon tumor cell differentiation. Inflammation induced by enterotoxigenic Bacteroides fragilis (ETBF) colonization of multiple intestinal neoplasia (MinApcΔ716/+) mice triggers loss of heterozygosity of Apc causing colon tumor formation. Here, we report that the addition of BRAFV600E mutation (BRAFF-V600ELgr5tm1(Cre/ERT2)CleMinApcΔ716/+, BLM) or knocking out Msh2 (Msh2LoxP/LoxPVil1-creMinApcΔ716/+, MSH2KO) in the Min model altered colon tumor differentiation. Using single-cell RNA sequencing, we uncovered the differences between BLM, Min, and MSH2KO tumors at a single-cell resolution. BLM tumors showed an increase in differentiated tumor epithelial cell lineages and a reduction in the tumor stem cell population. Interestingly, the tumor stem cell population of BLM tumors had revival colon stem cell characteristics with low WNT signaling and an increase in RevCSC marker gene expression. In contrast, MSH2KO tumors were characterized by an increased tumor stem cell population that had higher WNT signaling activity compared to Min tumors. Furthermore, overall BLM tumors had higher expression of transcription factors that drive differentiation, such as Cdx2, than Min tumors. Using RNA velocity, we identified additional potential regulators of BLM tumor differentiation such as NDRG1. The role of CDX2 and NDRG1 as putative regulators for BLM tumor cell differentiation was verified using organoids derived from BLM tumors. Our results demonstrate the critical connections between genetic mutations and cell differentiation in inflammation-induced colon tumorigenesis. Understanding such roles will deepen our understanding of inflammation-associated colon cancer. [ABSTRACT FROM AUTHOR]

* Context.--Recent molecular discoveries have led to improved understanding of tumor biology and the development of new diagnostic assays. Objective.--To review primarily 3 examples of liver tumors and to briefly illustrate how recent molecular discoveries have altered clinical liver pathology practice. Data Sources.--First, we will discuss fibrolamellar carcinoma, which will be the main focus of discussion, as an example for new diagnostic tests that have been developed as a result of molecular discoveries. Additional information on the role of molecular diagnostics in hepatocellular adenoma and hepatocellular carcinoma will be provided. Second, we will use the example of epithelioid hemangioendothelioma as an example of how new diagnostic tools, based on molecular discoveries, may support improved prognostication. Finally, we will use the example of intrahepatic cholangiocarcinoma as an example of a liver tumor where new molecular discoveries have identified tractable therapeutic targets and led to new effective therapies. This portion of the manuscript will also include a description of the anatomic and molecular differences between intrahepatic, hilar, and extrahepatic cholangiocarcinoma. Conclusions.--Fueled by molecular discoveries, new and better diagnostic tests and therapeutic targets have improved clinical care in patients affected by liver tumors. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor of kidney epithelial cells, one of the most common tumors in the world. Transforming growth factor beta (TGFβ)1 is a crucial factor that induces epithelial–mesenchymal transition (EMT) in cancer cells. microRNA-141-3p (miR-141-3p) is a microRNA that is considered a tumor suppressor. However, the role and mechanism of miR-141-3p in TGFβ1-induced ccRCC cells are not fully understood. This study investigated the roles of miR-141-3p and its target gene in regulating EMT in ccRCC development. 786-0 and Caki-1cells were treated with TGFβ1 to induce EMT. The levels of miR-141-3p and TGFβ2 were determined by quantitative real-time polymerase chain reaction and Western blotting. The progression of EMT was evaluated by E-cadherin detection by immunofluorescence, and E-cadherin, N-cadherin, and vimentin detection by Western blotting. Furthermore, migration and invasion capacities were assessed using a Transwell system. The direct binding of miR-141-3p with the target gene TGFβ2 was confirmed by dual luciferase reporter gene assay. Results indicated that TGFβ1 treatment decreased the protein abundance of E-cadherin while increasing the protein expression of N-cadherin and vimentin, indicating TGFβ1-induced EMT was constructed successfully. Moreover, TGFβ1 treatment repressed the expression of miR-141-3p. miR-141-3p mimics reversed the effect of TGFβ1 on the migration, invasion, and expression of E-cadherin, N-cadherin, and vimentin. The miR-141-3p directly binds with the 3′ untranslated region of TGFβ2 mRNA and suppresses its expression. Furthermore, TGFβ2 overexpression abrogated the above changes regulated by miR-141-3p mimics. Taken together, miR-141-3p inhibited TGFβ1-induced EMT by suppressing the migration and invasion of ccRCC cells via directly targeting TGFβ2 gene expression. [ABSTRACT FROM AUTHOR]

Simple Summary: Nowadays, tumor tests to analyze DNA in tumor cells from epithelial tubal/ovarian cancers (EOCs) are performed in many centers to detect tumor pathogenic variants (TPVs) in the BRCA1/2 genes. Information on the presence of these TPVs guides treatment options and further genetic testing in patients and relatives. However, there is no standardization of testing procedures, and information about how testing is performed is limited. Therefore, we described how BRCA1/2 tumor testing is performed in 999 EOC patients in the Netherlands in 2019 using real-world clinical data. Tumor tests were performed for 502 patients (50.2%) and TPVs were detected in 14.7% of the tests. This study shows that there is variability in the execution of BRCA1/2 tumor tests, but there were no indications for quality differences. Adequate reporting and quality monitors are essential to ensure that all centers perform reliable tumor tests to ultimately identify all patients with BRCA1/2 TPVs. Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOCs) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for the high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymic epithelial tumors are a rare and mostly indolent type of solid tumors. Histology, tumor staging, and resection status are important indicators of prognosis. Preoperative therapy is utilized in patients with advanced thymic tumors when primary surgery is unlikely to achieve R0 resection. By administering preoperative therapy, clinicians hope to have a better chance of resecting the tumor completely so that the patient may have a better prognosis. Many retrospective and a few prospective studies have been conducted in the past two decades on preoperative therapy. Also, many novel agents have recently entered the field of thymic tumor treatment. This review is a re-examination of the current evidence. For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: The triage of glandular cell abnormalities of the uterine cervix poses many challenges due to high interobserver variability. p16/Ki67 dual staining has been proposed as an objective test that could decrease interobserver variability in diagnosing atypical glandular cells. Our results indicate the possible role of p17/Ki67 dual staining in triaging glandular cell abnormalities. Very limited information exists about the role of p16/Ki67 dual staining on glandular cells in detecting glandular precancerous lesions and cervical adenocarcinoma. In this study, we investigated the diagnostic accuracy of p16/Ki67 dual staining for the detection of glandular and squamous lesions on the uterine cervix and for cancer of the upper reproductive tract. We performed a retrospective analysis of prospectively collected data on 96 patients with glandular cell abnormalities. We analyzed the diagnostic accuracy of p16/Ki67 dual staining for atypical glandular cells, not otherwise specified (AGC-NOS); atypical glandular cells, favor neoplastic (AGC-FN); adenocarcinoma in situ (AIS); and A-CA (cervical adenocarcinoma). A separate analysis for the detection of squamous precancerous lesions and squamous-cell carcinoma (CIN3+) and for cancer of the upper reproductive tract (EC/OC) was performed. Among patients who had normal histology or a low-grade lesion on final analysis, only 8.5% had positive dual staining. On the other hand, 85.7% of patients with AIS+ on final histology had positive dual staining. The respective specificities of p16/Ki67 dual staining on AGC-NOS for the detection of AIS+ (adenocarcinoma in situ or cervical adenocarcinoma), CIN3+ and EC/OC were 91.5%, 88.7% and 86.4%. High specificity values of p16/Ki67 dual staining on cervical smears labelled as AGC-NOS for the detection of CIN3+ and AIS+ suggest that this method might be a useful addition in cervical cancer screening. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the value of histogram analysis of postcontrast T1-weighted (T1C) and apparent diffusion coefficient (ADC) images in predicting the grade and proliferative activity of adult intracranial ependymomas. Methods: Forty-seven adult intracranial ependymomas were enrolled and underwent histogram parameters extraction (including minimum, maximum, mean, 1st percentile (Perc.01), Perc.05, Perc.10, Perc.25, Perc.50, Perc.75, Perc.90, Perc.95, Perc.99, standard deviation (SD), variance, coefficient of variation (CV), skewness, kurtosis, and entropy of T1C and ADC) using FireVoxel software. Differences in histogram parameters between grade 2 and grade 3 adult intracranial ependymomas were compared. Receiver operating characteristic curves and logistic regression analyses were conducted to evaluate the diagnostic performance. Spearman's correlation analysis was used to evaluate the relationship between histogram parameters and Ki-67 proliferation index. Results: Grade 3 intracranial ependymomas group showed significantly higher Perc.95, Perc.99, SD, variance, CV, and entropy of T1C; lower minimum, mean, Perc.01, Perc.05, Perc.10, Perc.25, Perc.50 of ADC; and higher CV and entropy of ADC than grade 2 intracranial ependymomas group (all p < 0.05). Entropy (T1C) and Perc.10 (ADC) had a higher diagnostic performance with AUCs of 0.805 and 0.827 among the histogram parameters of T1C and ADC, respectively. The diagnostic performance was improved by combining entropy (T1C) and Perc.10 (ADC), with an AUC of 0.857. Significant correlations were observed between significant histogram parameters of T1C (r = 0.296–0.417, p = 0.001–0.044) and ADC (r = -0.428–0.395, p = 0.003–0.038). Conclusion: Whole-tumor histogram analysis of T1C and ADC may be a promising approach for predicting the grade and proliferative activity of adult intracranial ependymomas. [ABSTRACT FROM AUTHOR]

Background and aims: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. Patients and methods: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. Results: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. Conclusion: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors have revolutionized cancer therapy and improved clinical outcomes. Immunotherapy is now increasingly combined with chemotherapy and other conventional treatments, such as radiation therapy, as part of the multimodal treatment of earlier-stage cancers. Although generally well tolerated and capable of inducing long-lasting responses, immunotherapy for thymic epithelial tumors can be challenging due to defects in immune self-tolerance, which increase the risk of immune-mediated toxicity. In order to improve the safety of immunotherapy and maximize clinical benefit in patients with thymic cancers, there is a pressing need to identify potential biomarkers of response and toxicity for this patient population. In this paper, we review the current role of immunotherapy for thymic cancers and discuss future applications across the spectrum of stage and histology of these diseases. Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low tumor mutation burden, a lack of actionable genomic changes, and, especially with thymomas, defects in immune tolerance. Surgery is the mainstay of the management of resectable disease, whereas advanced, unresectable tumors are treated with platinum-based chemotherapy. Disease recurrence can occur months to years after frontline treatment. Although several options are available for conventional treatment of recurrent thymic tumors, response rates are generally low, and treatment-related toxicity can affect quality of life. A subset of patients benefit from biologic therapies, but there remains an unmet need for the development of new treatments. Immune checkpoint inhibitors are safe, clinically active, and have contributed to an improvement in survival for patients with a wide variety of cancers. However, the application of these revolutionary treatments for thymic cancers is limited to their use for the management of recurrent thymic carcinoma because of the risk of immune toxicity. In this paper, we review the current uses of immunotherapy for the management of thymic epithelial tumors and highlight potential strategies to improve safety and broaden the application of these treatments for patients with thymic cancers. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to highlight the histopathological synopsis of ovarian lesions with emphasis on functional ovarian cysts and to compare our study with findings of other centers. Materials and Methods: Hematoxylin and eosin stained- slides of ovarian biopsies diagnosed at the Index Medical College and Research Centre, Indore, M.P. India over the period of three years. Results: A total of 117 ovarian cases were reviewed. Of this, 87 (74.35%) were nonneoplastic and 30 (25.64%) were neoplastic tumors. Out of the 117 nonneoplastic (follicular cysts) lesions, simple cyst lesions was the most commonly encountered, constituting 49 (41.88%). The peaks age incidence for nonneoplastic and benign neoplastic lesions occurred in the 4th decade. Two peaks age incidence was noted for malignant tumors 3rd to 5th decades. Epithelial cell tumor constituted the most common neoplastic ovarian tumor (n = 20; 17.09%) diagnosed. Conclusion: Functional ovarian cysts were the most commonly encountered ovarian lesions in our locality. The most common variety of functional cyst was Follicular cyst and simple serous cyst with majority occurring in the reproductive age groups. Among the ovarian tumors, Epithelial cell tumors were the most commonly seen. [ABSTRACT FROM AUTHOR]

Simple Summary: Sinonasal cancers (SNCs) are rare tumours of the nasal cavity and paranasal sinuses with recognised or suspected associations with some occupational carcinogens, including wood and leather dusts and nickel and chromium compounds. In Italy, a population-based SNC registry organised as a network of regional registries was officially established in 2008 to monitor SNC occurrence and evaluate occupational exposure. In this study, we analysed survival of SNC patients based on the SNC registry of the Lombardy region, north-west Italy (10 million people, one-sixth of the Italian population). In 2008–2020, we recorded more than 800 cases. Vital status was determined until mid-2023. About 50% of patients died within 5 years of diagnosis. Survival was strongly dependent on patients' age (worst prognosis in the elderly), tumour location (worst prognosis for paranasal sinuses), and for some histological types. Survival has not improved in recent years. Women and men had a similar prognosis. Sinonasal cancers (SNCs) are rare malignancies associated with occupational exposures. The aim of this study was to analyse the survival of SNC patients using data from the population-based SNC registry of the Lombardy region (10 million people), Italy. We included epithelial SNC cases registered in 2008–2020 and followed-up for vital status until 31 July 2023. Multivariate flexible parametric models with time-dependent covariates were fitted to calculate excess hazard ratios (EHRs) and 95% confidence intervals (CIs) of death. Based on 827 cases (553 males, 274 females) and 514 deaths (345 males, 169 females), the 5-year observed survival was 49% and the net survival was 57%. Age had a substantial impact on survival, particularly within the first year (EHR, 1.35; 95% CI, 1.12–1.51 per 10 years). Compared with the nasal cavity, the EHR for paranasal sinuses was 4.70 (95% CI, 2.96–7.47) soon after diagnosis. Compared with squamous cell carcinomas, the EHR was 0.69 (95% CI, 0.52–0.91) for adenocarcinomas, 1.68 (95% CI, 1.20–2.35) for undifferentiated and unspecified carcinomas, and 1.78 (95% CI, 1.07–2.95) for neuroendocrine carcinomas. Age and cancer site showed time-dependent effects on prognosis, especially within the first month after diagnosis. Prognosis was also markedly affected by cancer morphology. No associations were found for gender and period of diagnosis. [ABSTRACT FROM AUTHOR]

A 49-year-old man, a farmer, had been experiencing coughing, phlegm, and difficulty breathing for 2 months. He underwent a CT scan at a local hospital that showed a mediastinal mass. Bronchoscopy showed no obstruction in the tracheal lumen, and an endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) biopsy was performed on the mediastinal mass. The cytologic smear of the mediastinal mass showed a few atypical epithelial cells; the possibility of a tumor could not be ruled out. The patient visited our thoracic surgery outpatient department; based on the advice of the thoracic surgeon, the patient underwent another endobronchial ultrasound-guided transbronchial fine needle aspiration biopsy of the mediastinal mass 4 days before this admission. The patient went home and waited for the results. Two days later, the patient experienced a fever and palpitations accompanied by chills, yellow phlegm, and orthopnea. The patient visited our ED, underwent tracheal intubation, and was admitted to our ICU. The patient had had occasional coughing and phlegm for the past 10 years, which were not taken seriously or investigated. The patient does not smoke or drink alcohol, and there is no history of cancer in the family. [ABSTRACT FROM AUTHOR]

Background: Although there are great expectations regarding the use of tumor‐infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. Methods: We objectively investigated the prognostic significance of tumor‐infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ‐LC). Among patients who underwent surgical resection of SQ‐LC in 2011–2017, 100 patients with pathological stage IA3‐III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse‐free survival was analyzed using a Kaplan–Meier survival analysis and multivariate analyses using Fine‐Gray and Cox proportional hazards models. Results: The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29–1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21–1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91–7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. Conclusion: Our study provided partial but important information on the significance of CD8 + TILs in SQ‐LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed. [ABSTRACT FROM AUTHOR]

Background: Thymic epithelial tumors (TETs) are rare malignant tumors with limited treatment options. No established second‐line treatment regimen is available following the preferred first‐line chemotherapy, resulting in unsatisfactory efficacy and poor prognosis for patients with advanced TETs. This study aimed to evaluate the efficacy of small molecule multitarget antiangiogenic inhibitors as well as the prognostic factors for advanced TETs. Methods: A retrospective study was conducted using data from a real‐world database. Clinical information and survival follow‐up data were collected from 52 patients with advanced TETs who received small molecule multitarget antiangiogenic inhibitors at Zhejiang Cancer Hospital between August 10, 2016 and August 10, 2022. The short‐term efficacy of the treatments, survival time of the patients, and relevant prognostic factors of advanced TETs were analyzed. Results: Out of the 52 patients included in this study, 16 had thymoma and 36 had thymic carcinoma. The 52 patients had an overall response rate of 21.1% and a disease control rate of 94.2%. In addition, the median progression‐free survival (PFS) was 8.05 months, and the overall survival (OS) was 25.00 months. Apatinib was given to 33 patients, anlotinib to 15 patients, and sunitinib or lenvatinib to four patients. Only seven patients received antiangiogenic inhibitors as their first‐line therapy, 27 patients as their second‐line therapy, and 18 patients as third‐line or subsequent therapy. Meanwhile, 42 patients received monotherapy with an antiangiogenesis inhibitor, while 10 patients received combination therapy. Univariate analysis indicated that the combined treatment was associated with a superior OS (p = 0.044); multivariate analysis indicated that the combined treatment was an independent prognostic factor for PFS (p = 0.014) and OS (p = 0.012). Conclusion: The findings suggest that small molecule multitarget antiangiogenic inhibitors are efficacious as second or post‐line treatments as a viable alternative treatment option for patients with advanced TETs. [ABSTRACT FROM AUTHOR]

Simple Summary: Romania ranks second in Europe in both mortality and incidence rates for cervical cancer, and the majority of cases are diagnosed in locally advanced stages. Therapeutic guidelines indicate concomitant chemoradiotherapy as the proper treatment (total dose 85–90 Gy at point A). Yet, in Romania, as a result of poor radiotherapy infrastructure, deficient patient access to radiotherapy, and specific socio-psychologic factors, concurrent chemoradiotherapy is usually suboptimal (total dose 60–65 Gy at point A) and often followed by radical surgery aimed at better local control. Our retrospective cohort study of 351 patients with histopathological confirmed locally advanced cervical cancer proved that complete pathologic response is present in less than half of patients previously treated by concurrent chemoradiotherapy, thus demonstrating the rationale behind radical surgery—better local control, especially in unfavorable aggressive histological types like adenocarcinoma and adenosquamous carcinoma or tumors that have progressed under concurrent chemoradiotherapy. We discuss several possible causes for the over-usage of surgery in Romania for treating locally advanced cervical cancer. The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85–90 Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemoradiotherapy (total dose 60–65 Gy at point A), followed by surgery, which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated-on patients compared to 62% for non-operated-on patients receiving suboptimal concurrent chemotherapy alone. In conclusion, in Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic or inoperable thymic carcinoma (TC) has a very poor prognosis. Since this tumor is rare, few clinical trials have been conducted to date, and thus, the development of new drugs is slow. The aberrant pathways involved in TC need to be examined in more detail in order to identify novel target molecules for TC therapy. Next-generation sequencing has been used to comprehensively investigate genetic alterations in thymic epithelial tumors (TET). However, limited information is currently available on epigenetic alterations. In the present study, genome-wide screening was conducted on aberrantly methylated CpG islands in TET, and 92 genes were identified. We then focused on the DNA methylation and mRNA and protein expression of NPTX2 in TET. The DNA methylation level of NPTX2 was higher, while its mRNA and protein expression levels were lower in TC than in the normal thymus and thymoma. Furthermore, relapse-free survival was shorter in patients with high NPTX2 DNA methylation levels than in those with low DNA methylation levels. Collectively, the present results indicate the potential use of NPTX2 as a tumor suppressor in TC. Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET have been the focus of recent research. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in TET, and this identified neuronal pentraxin 2 (NTPX2) as a significantly hypermethylated CpG island in TC relative to thymomas. NPTX2 is released from pre-synaptic cells in response to neuronal activity/seizure, and plays a role in host immunity and acute inflammation. TET samples were obtained from 38 thymomas, 25 TC, and 6 NECTT. The DNA methylation, mRNA, and protein expression levels of NPTX2 were examined. The DNA methylation rate of the NPTX2 gene was significantly higher in TC than in the normal thymus and thymomas, except B3. The mRNA expression level of NPTX2 was lower in TC than in the normal thymus. An inverse relationship was observed between mRNA expression levels and methylation levels. Relapse-free survival was shorter in patients with high NPTX2 DNA methylation levels than in those with low DNA methylation levels. NECTT showed very high mRNA and protein expression levels and low DNA methylation levels of NPTX2. NPTX2 may function as a tumor suppressor in TC, and have an oncogenic function in NECTT. [ABSTRACT FROM AUTHOR]

Simple Summary: Esophageal adenocarcinoma is a type of cancer that originates in cells lining the lower part of the esophagus, the tube that connects the throat to the stomach. This cancer specifically arises from glandular cells, which produce mucus to help lubricate the lining of the esophagus. In this work, we investigated whether and to what extent truncated O-glycans, called Tn and STn antigens, are expressed under pathophysiological conditions and whether these correlate with clinicopathological data and overall survival. This investigation is particularly significant in the context of targeted therapies, since Tn and STn antigens are tumor-specific target structures. Differential glycosylation, marked by the presence of truncated O-glycans, is a distinctive feature of epithelial-derived cancers. However, there is a notable gap in research regarding the expression of Tn and STn antigens in esophageal adenocarcinoma (EAC). To address this, we employed commercially available antibodies, previously validated for Tn and STn antigens, to analyze two cohorts of EAC tissues. Initially, large-area tissue sections from formalin-fixed paraffin-embedded (FFPE) EAC and corresponding healthy tissues were subjected to immunohistochemistry (IHC) staining and scoring. Subsequently, we evaluated the RNA expression levels of crucial O-glycosylation related genes—C1GALT1 and C1GALT1C1—using a quantitative real-time polymerase chain reaction (qRT-PCR). In a comprehensive analysis, a substantial cohort of EAC tissues (n = 311 for Tn antigen, n = 351 for STn antigen) was investigated and correlated with clinicopathological data. Our findings revealed that Tn and STn antigens are highly expressed (approximately 71% for both) in EAC, with this expression being tumor-specific. Notably, Tn antigen expression correlates significantly with the depth of tumor cell infiltration (p = 0.026). These antigens emerge as valuable markers and potential therapeutic targets for esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background. Pseudomyxoma peritonei (PMP) is a form of peritoneal malignancy. It originates from a perforated appendiceal epithelial tumour. Patients with PMP experience various stressful and traumatic events including diagnosis with a rare disease, treatment with extensive and complex surgery, and long hospital stays. Currently, there is a scarcity of studies that primarily aim to assess the quality of life of patients with PMP, and there is no reviews or comprehensive understanding of the quality of life (QoL) issues faced by these patients. Even fewer studies have consulted with patients themselves. Objective. To review the current literature on the QoL of patients with PMP and answer two main questions: What methods are being used to assess the QoL patients with PMP and what are the main findings?. Methods. For the scoping review, five scientific databases were searched (CINAHL, EMBASE, Pubmed, PsycInfo, and Medline). Publications that were published between 2002 and 2022 and in English were included in this review. Studies were screened by two independent reviewers against the review's eligibility criteria. Data related to the QoL of patients with PMP in the included studies were extracted to answer two main questions (what were the methods used to assess QoL in this population, and what were the findings?). The extracted data was presented in table form and qualitatively analyzed using content analysis. Findings. Fourteen studies were included in this review. Only five studies out of fourteen assessed the QoL of patients with PMP as a main outcome, and all these studies assessed QoL in relation to surgery. Studies that assessed QoL used different validated measures. There was a consensus among studies that patients' QoL improved by 12 months posttreatment. The most commonly cited symptom of PMP in this review is abdominal pain. Conclusion. The evidence on the QoL of patients with PMP is limited. Studies that assess the quality of life of these patients independent of surgery are needed. There is no consensus on the measure used to assess QoL in this population. [ABSTRACT FROM AUTHOR]

Forkhead box protein 3 (FOXP3), traditionally recognized as a specific transcription factor for regulatory T cells (Tregs), has also been identified in various tumor epithelial cells (named as cancer-FOXP3, c-FOXP3). However, the natural state and functional role of FOXP3 positive tumor epithelial cells remain unknown. Monoclonal cells expressing varying levels of c-FOXP3 were isolated from established PANC-1 cells using limited dilution. Whole transcriptome sequencing and weighted gene co-expression network analysis (WGCNA) were conducted on these subsets, followed by in vitro and in vivo functional investigations. In addition, we identified c-FOXP3+E-cadherin- epithelial cells in human pancreatic cancer tissues after radical resection by immunofluorescence co-staining. We also investigated the connection between c-FOXP3+E-cadherin- epithelial cells and their clinicopathological features. Our study uncovered a distinct subset of c-FOXP3+ tumor epithelial cells characterized by reduced E-cadherin expression. C-FOXP3+E-cadherin- cells displayed significant proliferation potential and pro-angiogenic effect through the expression of chemokines, including C-X-C motif ligand 1 (CXCL1), C-X-C motif ligand 5 (CXCL5), and C-X-C motif ligand 8 (CXCL8). Notably, higher counts of c-FOXP3+E-Cadherin- cells correlated with poorer prognosis, lower tumor differentiation, lymph node metastasis, and vascular invasion in pancreatic ductal adenocarcinoma (PDAC). In conclusion, this work revealed the stable expression of FOXP3 in tumor epithelial cells, marking a distinct subset. C-FOXP3+E-cadherin- epithelial cells exhibit active proliferation and promote angiogenesis in a vascular endothelial growth factor A (VEGFA) independent manner. These findings provide novel insights into PDAC prognosis and therapeutic avenues. NEW & NOTEWORTHY: In this study, we revealed a novel c-FOXP3+ tumor epithelial cell subset marked by diminished E-cadherin and stable FOXP3 expression. These subpopulations not only show robust proliferation and drive angiogenesis via CXCL1, CXCL5, and CXCL8, bypassing VEGFA pathways, but their heightened presence also correlates with adverse PDAC outcomes. By challenging traditional epithelial cell definitions and extending lymphocyte markers to these cells, our findings present innovative targets for PDAC treatment and enrich our understanding of cell biology. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymic carcinomas are the most aggressive thymic epithelial tumors. While thymic carcinomas do not have a single specific cause, various aspects of their growth have been evaluated at the molecular level. In this review, we organize the recent findings according to what have been defined as the hallmarks of cancer. The identification of the molecular alterations that drive the growth of these tumors is crucial for the development of effective target therapies. Inactivation of CDKN2A, TP53, and CDKN2B by somatic mutation or deletion is most common in thymic carcinomas. In advanced tumors, mutations in genes that regulate epigenetic and chromatin remodeling can occur. On the contrary, mutations in tyrosine kinase receptors and other oncogenes are only occasional, with those of KIT being the most common and present in only 10% of thymic carcinomas. Thymic carcinomas present an enhanced and aberrant vasculature that has been targeted in clinical trials with promising results. Additionally, thymic carcinomas evade the control of the immune system, with some tumors showing a response to immune checkpoint inhibitors. Thymic epithelial tumors, comprising thymic carcinomas and thymomas, are rare neoplasms. They differ in histology, prognosis, and association with autoimmune diseases such as myasthenia gravis. Thymomas, but not thymic carcinomas, often harbor GTF2I mutations. Mutations of CDKN2A, TP53, and CDKN2B are the most common thymic carcinomas. The acquisition of mutations in genes that control chromatin modifications and epigenetic regulation occurs in the advanced stages of thymic carcinomas. Anti-angiogenic drugs and immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have shown promising results for the treatment of unresectable tumors. Since thymic carcinomas are frankly aggressive tumors, this report presents insights into their oncogenic drivers, categorized under the established hallmarks of cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver tumours in children are definitely "surgical tumours", and their complete resection is essential for cure. Compared to adults, the extent of resection in children can be much greater; up to 75–85% of the liver parenchyma can be safely resected. However, parenchymal preservation resection (segmentectomy, bisegmentectomy) seems to be a good option in carefully selected patients. There are very few publications regarding minor liver resections in children. From the available literature and data presented here, we propose that (bi)segmentectomy can become a viable surgical option in patients with favourable tumour locations and the absence of portal invasion in imaging. But, when qualifying a child for minor resection, it is important to remember that meeting oncological goals remains the primary objective of liver surgery. Further studies evaluating the impact of parenchymal preservation surgery on surgical and oncological outcome after liver resection in children should be conducted with a larger dataset. Purpose: To present a single-centre experience in bi- and uni-segmentectomies for primary liver tumours in children. Methods: This study included 23 patients that underwent (bi)segmentectomy. There were 15 malignant tumours (hepatoblastoma—13 patients), 7 benign tumours, and 1 calcifying nested stromal epithelial tumour. Results: The median tumour diameter was 52 mm (range 15–170 mm). Bisegmentectomy 2–3 was most frequently performed (seven patients), followed by bisegmentectomy 5–6 (four patients). The median operative time was 225 min (range 95–643 min). Intraoperative complications occurred in two patients—small bowel perforation in one and an injury of the small peripheral bile duct resulting in biloma in the other. The median resection margin in patients with hepatoblastoma was 3 mm (range 1–15 mm). Microscopically negative margin status was achieved in 12 out of 13 patients. There were two recurrences. After a median follow-up time of 38 months (range 12–144 months), all 13 patients with HB were alive with no evidence of disease. Two relapsed patients were alive with no evidence of disease. Conclusions: From the available literature and data presented here, we propose that (bi)segmentectomy can become a viable surgical option in carefully selected paediatric patients and is sufficient to achieve a cure. Further studies evaluating the impact of parenchymal preservation surgery on surgical and oncological outcome should be conducted with a larger dataset. [ABSTRACT FROM AUTHOR]

Intra-tumor heterogeneity contributes to treatment failure and poor survival in urothelial bladder carcinoma (UBC). Analyzing transcriptome from a UBC cohort, we report that intra-tumor transcriptomic heterogeneity indicates co-existence of tumor cells in epithelial and mesenchymal-like transcriptional states and bi-directional transition between them occurs within and between tumor subclones. We model spontaneous and reversible transition between these partially heritable states in cell lines and characterize their population dynamics. SMAD3, KLF4 and PPARG emerge as key regulatory markers of the transcriptional dynamics. Nutrient limitation, as in the core of large tumors, and radiation treatment perturb the dynamics, initially selecting for a transiently resistant phenotype and then reconstituting heterogeneity and growth potential, driving adaptive evolution. Dominance of transcriptional states with low PPARG expression indicates an aggressive phenotype in UBC patients. We propose that phenotypic plasticity and dynamic, non-genetic intra-tumor heterogeneity modulate both the trajectory of disease progression and adaptive treatment response in UBC. A set of functional genomics and statistical analyses identifies and establishes key determinants of transcriptional state dynamics and plasticity during tumor growth and under treatment in urothelial bladder carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: "Driver gene-negative" non-small cell lung cancer (NSCLC) currently has no approved targeted drug, due to the lack of common actionable driver molecules. Even though miRNAs play crucial roles in various malignancies, their roles in "driver gene-negative" NSCLC keep unclear. Methods: miRNA expression microarrays were utilized to screen miRNAs associated with "driver gene-negative" NSCLC malignant progression. Quantitative real-time PCR (RT-qPCR) and in situ hybridization (ISH) were employed to validate the expression of miR-4739, and its correlation with clinicopathological characteristics was analyzed in tumor specimens using univariate and multivariate analyses. The biological functions and underlying mechanisms of miR-4739 were investigated both in vitro and in vivo. Results: our research demonstrated, for the first time, that miR-4739 was substantially increased in "driver gene-negative" NSCLC tumor tissues and cell lines, and overexpression of miR-4739 was related to clinical staging, metastasis, and unfavorable outcomes. Functional experiments discovered that miR-4739 dramatically enhanced tumor cell proliferation, migration, and metastasis by promoting the epithelial-to-mesenchymal transition (EMT). Meanwhile, miR-4739 can be transported from cancer cells to the site of vascular epithelial cells through exosomes, consequently facilitating the proliferation and migration of vascular epithelial cells and inducing angiogenesis. Mechanistically, miR-4739 can activate Wnt/β-catenin signaling both in tumor cells and vascular epithelial cells by targeting Wnt/β-catenin signaling antagonists APC2 and DKK3, respectively. Conclusion: Our work identifies a valuable oncogene, miR-4739, that accelerates malignant progression in "driver gene-negative" NSCLC and serves as a potential therapeutic target for this group of tumors. [ABSTRACT FROM AUTHOR]

Context.-- Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva's anatomic location. Objectives.-- To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties. Design.-- One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6). Results.-- Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95, 1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96, 1.20, and 1.08, respectively; P < .001). Conclusions.-- There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN. [ABSTRACT FROM AUTHOR]

Treatment patterns in locally advanced and metastatic urothelial bladder cancer (La/mUBC) is changing, but little is known about current treatment patterns, survival, and costs of these patients. Our aim was to describe treatment patterns, survival, and healthcare utilisation/costs in Danish La/mUBC patients in a routine clinical care setting. Registry-based nationwide cohort study including all bladder cancer patients aged 18 years or older with a La/mUBC tumour in the pathology register and a concomitant bladder cancer diagnosis in the Danish National Patient Registry in the period 2015–2020. We categorised the patients according to (1) La/mUBC at time of first bladder cancer diagnosis (de novo La/mUBC) and (2) non-invasive or localised muscle-invasive bladder cancer at time of diagnosis which had progressed to La/mUBC. All patients were included at date of pathology-confirmed La/mUBC. Follow-up ended 30 September 2022. We identified 1278 patients (69% men) with La/mUBC and no other previous cancer. Of these, 212 (17%) had de novo La/mUBC, while 1066 (83%) had progressed to La/mUBC. Median age was 72 years. Patients were followed for a median of 13.0 months (interquartile range 4.7;32.0). During follow-up, 651 (51%) patients started first-line treatment, of these, 285 progressed to second-line treatment, and 112 also started third-line treatment. Median survival was 13.0 months from La/mUBC diagnosis, 12.1 months from start of first-line treatment, 9.8 months from start of second-line treatment, and 8.6 months from start of third-line treatment. The mean number of days admitted to hospital was 3.47, 3.97, and 4.07 per month following initiation of first-line, second-line, and third-line treatment, respectively. Patients with La/mUBC have a poor prognosis, and in routine clinical care only around half of the patients received systemic anti-cancer treatment suggesting an unmet need for novel treatments. The overall costs only increased slightly from first to third-line treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer (BC) is one of the most common urological cancers affecting more men than women. The absence of biomarkers for early detection and prognostication add to the burden of the disease. The SPP1 protein is differentially expressed in many malignancies and could serve as a potential prognostic biomarker. However, its expression profile, clinical significance and prognostic value, as well as its relationship with immune infiltration, have not been comprehensively studied in bladder cancer. Herewith, we aimed to investigate the prognostic value of SPP1 expression and its association with other cancer-promoting factors in bladder cancer. Our data indicated that SPP1 is differentially expressed at an early stage of BC development and is associated with an unfavorable prognosis. Interaction between SPP1 and other proteins/genes and immune cell infiltrates may play an important role in the pathogenesis and could as a potential therapeutic target for bladder cancer. Secreted phosphoprotein-1 (SPP1) expression is differentially altered in many malignancies and could serve as a potential prognostic biomarker. Recent findings indicated that SPP1 possesses a broader role in bladder cancer (BC) pathogenesis than previously envisioned; however, the underlying mechanisms governing its expression, cellular localization, prognostic value and immune-related role in bladder cancer remain poorly understood. The expression and the prognosis value of SPP1 were assessed using immunohistochemistry (IHC) staining on a tissue microarray. SPP1 expression was correlated with the clinicopathological parameters, and survival analysis was calculated using a Kaplan–Meier plotter. Bioinformatics analysis of TCGA data was queried using UALCAN, CIBERSORT and TIMER datasets to decipher the biological processes enrichment pattern, protein–protein interactions and characterize tumor-infiltrating immune cells, respectively. IHC revealed that SPP1 expression is significantly associated with tumor type, stage, grade and smoking status. The Kaplan–Meier survival curve showed that low SPP1 expression is an unfavorable prognostic indicator in bladder cancer patients (p = 0.02, log-rank). The significant increased expression of the SPP1 level is associated with evident hypomethylation of the gene promoter in cancer compared to normal tissues in the TCGA-bladder dataset. Missense mutation is the most frequent genetic alteration of the SPP1 gene. Protein–protein interactions demonstrated that SPP1 shares the same network with many important genes and is involved in many signaling pathways and biological processes. TIMER reported a significant correlation between SPP1 expression and multiple immune cells infiltration. Furthermore, the expression of SPP1 was found to be positively correlated with a number of immune checkpoint genes such as PD-1 and CTLA4. The current investigation indicates that the SPP1 protein could serve as a prognostic biomarker and merit further investigation to validate its clinical usefulness in patients with bladder cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: We investigated the prevalence of genetic alterations and their association with epidermal growth factor receptor (EGFR) mutations and prognosis in early-stage non-small cell lung cancer (NSCLC) after curative resection. The results showed that the prevalence of EGFR mutations, anaplastic lymphoma kinase (ALK) rearrangements, and ROS proto-oncogene 1 (ROS1) fusion were 43.0%, 5.7%, and 1.6%, respectively. Patients with EGFR-mutant NSCLC had a higher risk of recurrence than those without EGFR mutations. Additionally, EGFR mutations were related to a high proportion of distant metastases and a higher risk of central nervous system recurrence. A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458–4.993; p = 0.002), stage II (HR: 2.614; 95% CI: 1.29–5.295; p = 0.008) or III disease (HR: 9.537; 95% CI: 4.825–18.852; p < 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405–4.803; p = 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type (p = 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached; p = 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymic epithelial tumors (TET) are rare. Therefore, large studies, specifically concerning genetic alterations, are difficult in these tumors and require multi-institutional effort. However, such studies are important because alterations in certain genes of these tumors could be useful in the diagnosis of difficult cases, provide a better understanding of the nature of these tumors, or may even be therapeutically targetable. A few genetic alterations have already been identified in TET. This review will focus on gene fusions that have been reported in a subset of TET. The histopathologic features and clinical characteristics of these subtypes of TET and the potential clinical implications of the gene fusions for outcome of the patient and therapeutic options will be discussed. Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials. Gene fusions that have been identified in TET include MAML2 rearrangements in 50% to 56% of mucoepidermoid carcinomas (MAML2::CRTC1), 77% to 100% of metaplastic thymomas (YAP1::MAML2), and 6% of B2 and B3 thymomas (MAML2::KMT2A); NUTM1 rearrangements in NUT carcinomas (most commonly BRD4::NUTM1); EWSR1 rearrangement in hyalinizing clear cell carcinoma (EWSR1::ATF1); and NTRK rearrangement in a thymoma (EIF4B::NTRK3). This review focuses on TET in which these fusion genes have been identified, their morphologic, immunophenotypic, and clinical characteristics and potential clinical implications of the fusion genes. Larger, multi-institutional, global studies are needed to further elucidate the molecular characteristics of these rare but sometimes very aggressive tumors in order to optimize patient management, provide patients with the opportunity to undergo targeted therapy and participate in clinical trials, and to elucidate the pathogenesis of these tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Similarly to other solid malignancies, there is a growing interest in testing immune checkpoint inhibitors (ICIs) for thymic epithelial tumors (TETs). However, the thymus has unique biological features that can increase the risk of immune-related adverse events. In this article, the relationships among the thymus, immune system, and autoimmune diseases (ADs) usually associated with TETs, and their impact on the potential benefits and risks of immunotherapy, are reviewed. The results of completed clinical trials of immunotherapy for refractory/relapsed thymomas and thymic carcinomas are presented. Thymic epithelial tumors (TETs) comprise a rare group of thoracic cancers, classified as thymomas and thymic carcinomas (TC). To date, chemotherapy is still the standard treatment for advanced disease. Unfortunately, few therapeutic options are available for relapsed/refractory tumors. Unlike other solid cancers, the development of targeted biologic and/or immunologic therapies in TETs remains in its nascent stages. Moreover, since the thymus plays a key role in the development of immune tolerance, thymic tumors have a unique biology, which can confer susceptibility to autoimmune diseases and ultimately influence the risk–benefit balance of immunotherapy, especially for patients with thymoma. Indeed, early results from single-arm studies have shown interesting clinical activity, albeit at a cost of a higher incidence of immune-related side effects. The lack of knowledge of the immune mechanisms associated with TETs and the absence of biomarkers predictive of response or toxicity to immunotherapy risk limiting the evolution of immunotherapeutic strategies for managing these rare tumors. The aim of this review is to summarize the existing literature about the thymus's immune biology and its association with autoimmune paraneoplastic diseases, as well as the results of the available studies with immune checkpoint inhibitors and cancer vaccines. [ABSTRACT FROM AUTHOR]

This narrative review aims to provide a comprehensive overview of the current state of circulating tumor cell (CTC) analysis and its clinical significance in patients with epithelial cancers. The review explores the advancements in CTC detection methods, their clinical applications, and the challenges that lie ahead. By examining the important research findings in this field, this review offers the reader a solid foundation to understand the evolving landscape of CTC analysis and its potential implications for clinical practice. The comprehensive analysis of CTCs provides valuable insights into tumor biology, treatment response, minimal residual disease detection, and prognostic evaluation. Furthermore, the review highlights the potential of CTCs as a non-invasive biomarker for personalized medicine and the monitoring of treatment efficacy. Despite the progress made in CTC research, several challenges such as standardization, validation, and integration into routine clinical practice remain. The review concludes by discussing future directions and the potential impact of CTC analysis on improving patient outcomes and guiding therapeutic decision-making in epithelial cancers. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is one of the most common primary malignancies of the urinary tract, highly heterogeneous, and increasing in incidence worldwide. Anoikis is a specific type of programmed cell death in which solid tumor cells or normal epithelial cells that do not have metastatic properties lose adhesion to the extracellular matrix or undergo inappropriate cell adhesion-induced apoptosis. Anoikis is thought to play a critical role in tumorigenesis, maintenance, and treatment, according to an increasing amount of research. However, there is still some uncertainty regarding the general impact of anoikis-related genes (ARGs) on the prognostic importance, tumor microenvironment characteristics, and treatment reaction of ccRCC patients. For this study, we used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus datasets to access the RNA sequencing results and clinical information from ccRCC patients. 29 ARGs related to survival were found using differential analysis and univariate Cox regression analysis. The samples were then divided into two clusters that had different immune traits via unsupervised cluster analysis using 29 prognosis-associated differently expressed ARGs. Then, to build an ARGs signature, 7 genes (PLAU, EDA2R, AFP, PLG, TUBB3, APOBEC3G, and MALAT1) were found using Least Absolute Shrinkage and Selection Operator regression analysis. The new ARGs signature demonstrated outstanding prognostic capability for ccRCC patients' overall survival. In conclusion, for ccRCC patients, we created an ARGs signature that strongly connects to immunological traits and therapy response. Clinicians may find this ARGs signature helpful in developing more individualized and detailed treatment strategies for ccRCC patients. [ABSTRACT FROM AUTHOR]

Objective: We previously reported that dickkopf WNT signaling inhibitor 3 (DKK3) would modulate malignant potential of oral squamous cell carcinoma (OSCC) via activating Akt. Recently, cytoskeleton associated protein 4 (CKAP4) functions as receptor of DKK3, which activates Akt in esophageal squamous cell carcinoma, but its expression and function in OSCC were unclear. Methods: We studied DKK3 and CKAP4 protein expression in OSCC tissue and investigated the correlation between protein expression and clinical data. We also investigated whether antibodies (Ab) for DKK3 or CKAP4 could suppress malignant potential of the cancer cells. Results: DKK3/CKAP4 protein expression was observed in majority of OSCC cases and was associated with significantly higher T‐stage and TNM stage. Multivariate analysis revealed that DKK3 and CKAP4 were independent prognostic biomarkers for overall survival (OS) and disease‐free survival (DFS), respectively. Survival analyses revealed that DKK3‐positive cases and CKAP4‐positive cases showed significantly shorter OS and DFS, respectively, and that DKK3/CKAP4 double‐negative cases showed significantly favorable prognosis. Both anti‐DKK3Ab and anti‐CKAP4Ab could suppress cancer cell proliferation, migration, and invasion. Conclusion: DKK3/CKAP4 axis is thought to be important in OSCC, and it would be a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Verrucous carcinoma is a rare urological malignancy that primarily affects the penile area, with the upper urinary tract, particularly the ureter, being less common. The literature on verrucous carcinoma of the ureter is limited due to its rarity. There have been reports of verrucous carcinoma including oral verrucous carcinoma, cutaneous verrucous carcinoma, kidney verrucous carcinoma, and other types of verrucous carcinoma. We presented the world's first case of ureter verrucous carcinoma. [ABSTRACT FROM AUTHOR]

Background: Thymic epithelial tumors (TET) are rare malignancies and lack well‐defined biomarkers for neoadjuvant therapy. This study aimed to evaluate the clinical utility of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in TET. Methods: Patients initially diagnosed with unresectable thymoma or thymic carcinoma who underwent neoadjuvant therapy between January 2004 and December 2021 formed our study population. Hematoxylin and eosin‐stained sections from the initial biopsy and surgery were analyzed using an AI‐powered spatial TIL analyzer. Intratumoral TIL (iTIL) and stromal TIL (sTIL) were quantified and their immune phenotype (IP) was identified. Results: Thirty‐five patients were included in this study. The proportion of patients with partial response to neoadjuvant therapy was higher in the group with nondesert IP in preneoadjuvant biopsy (63.6% vs. 17.6%, p = 0.038). A significant increase in both iTIL (median 22.18/mm2 vs. 340.69/mm2, p < 0.001) and sTIL (median 175.19/mm2 vs. 531.02/mm2, p = 0.004) was observed after neoadjuvant therapy. Patients with higher iTIL (>147/mm2) exhibited longer disease‐free survival (median, 29 months vs. 12 months, p = 0.009) and overall survival (OS) (median, 62 months vs. 45 months, p = 0.002). Patients with higher sTIL (>232.1/mm2) exhibited longer OS (median 62 months vs. 30 months, p = 0.021). Conclusions: Nondesert IP in initial biopsy was associated with a better response to neoadjuvant therapy. Increased infiltration of both iTIL and sTIL in surgical specimens were associated with longer OS in patients with TET who underwent resection followed by neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Surgery is the cornerstone of the treatment of thymic epithelial tumors, and favorable results are observed after complete surgical treatment of early-stage tumors. In locally advanced tumors, induction and adjuvant treatments are associated with surgery to improve complete resection rate and long-term survival. Several issues concerning the surgical treatment of thymic tumors are nevertheless still a matter of discussion and have been therefore to be analyzed. Minimally invasive surgical approaches were increasingly used in the last years, but their role in the treatment of locally advanced tumors is still to be defined. Moreover, although extended thymectomy is considered the standard surgical approach, limited resections such as thymomectomy are also currently used in the treatment of early-stage thymomas. The role of systematic nodal dissection in the surgical treatment of thymomas has also to be defined. Other significant issues concern the role of induction and adjuvant treatments in locally advanced thymic tumors and the role of surgery in the treatment of tumor recurrences. The mainstays and future perspectives in the field were reviewed from MEDLINE and Scopus databases based on appropriate keywords. [ABSTRACT FROM AUTHOR]

Intracranial granulomas are a major cause of seizures in India, the most common etiologies being neurocysticercosis and tuberculosis. However, other pathologies including rare low-grade tumors may mimic these granulomas on imaging. In this article, we presented the case of a young woman patient with drug-resistant epilepsy. On imaging, there was a small calcified lesion in the brain parenchyma. In view of concordant electroclinical and imaging data on presurgical evaluation, the lesion was excised and the patient was seizure free. On histopathological evaluation, it was found to be a polymorphous low-grade neuroepithelial tumor of the young (PLNTY) – a rare, recently reported entity that can mimic an intracranial granuloma on imaging. [ABSTRACT FROM AUTHOR]

Background: This phase II trial was designed to evaluate the efficacy and safety of S‐1 combined with weekly irinotecan as a second‐ or third‐line treatment for patients with advanced or recurrent squamous cell lung cancer. Methods: Patients with a body surface area <1.25, 1.25–1.50, and >1.50 m2 received oral S‐1 on days 1–14 at 80, 100, and 120 mg/day, respectively, and irinotecan on days 1 and 8 at 70 mg/m2 every 3 weeks. The primary endpoint was the overall response rate, and the secondary endpoints were progression‐free survival, overall survival, and the incidence and severity of adverse effects. Results: Between September 2011 and December 2014, 30 patients were enrolled in this study. The overall response rate was 6.7% (95% confidence interval [CI]: 0.8%–22.1%), and the disease control rate was 73.3%. The median progression‐free survival was 3.0 months (95% CI: 2.5–3.4 months), and the median overall survival was 10.5 months (95% CI: 5.6–13.7 months). Grade 3/4 treatment‐related adverse events were reported in ≥10% of the patients, including leukopenia (21%), neutropenia (21%), anemia (17%), anorexia (10%), and hypokalemia (10%). Conclusions: Although the treatment‐related adverse events were manageable, the combination of weekly irinotecan and S‐1 did not have the expected effect. [ABSTRACT FROM AUTHOR]

Cancer is a dysregulated cellular level pathological condition that results in tumor formation followed by metastasis. In the heterogeneous tumor architecture, cancer stem cells (CSCs) are essential to push forward the progression of tumors due to their strong pro-tumor properties such as stemness, self-renewal, plasticity, metastasis, and being poorly responsive to radiotherapy and chemotherapeutic agents. Cancer stem cells have the ability to withstand various stress pressures by modulating transcriptional and translational mechanisms, and adaptable metabolic changes. Owing to CSCs heterogeneity and plasticity, these cells display varied metabolic and redox profiles across different types of cancers. It has been established that there is a disparity in the levels of Reactive Oxygen Species (ROS) generated in CSCs vs Non-CSC and these differential levels are detected across different tumors. CSCs have unique metabolic demands and are known to change plasticity during metastasis by passing through the interchangeable epithelial and mesenchymal-like phenotypes. During the metastatic process, tumor cells undergo epithelial to mesenchymal transition (EMT) thus attaining invasive properties while leaving the primary tumor site, similarly during the course of circulation and extravasation at a distant organ, these cells regain their epithelial characteristics through Mesenchymal to Epithelial Transition (MET) to initiate micrometastasis. It has been evidenced that levels of Reactive Oxygen Species (ROS) and associated metabolic activities vary between the epithelial and mesenchymal states of CSCs. Similarly, the levels of oxidative and metabolic states were observed to get altered in CSCs post-drug treatments. As oxidative and metabolic changes guide the onset of autophagy in cells, its role in self-renewal, quiescence, proliferation and response to drug treatment is well established. This review will highlight the molecular mechanisms useful for expanding therapeutic strategies based on modulating redox regulation and autophagy activation to targets. Specifically, we will account for the mounting data that focus on the role of ROS generated by different metabolic pathways and autophagy regulation in eradicating stem-like cells hereafter referred to as cancer stem cells (CSCs). [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced ovarian cancer (Stages III-IV) continues to be one of the gynecological tumors with the highest mortality. Standard treatment consists of debulking surgery and subsequent adjuvant chemotherapy. Recently, some authors have postulated that the administration of hyperthermic chemotherapy during surgery could increase the survival of patients, especially in cases in which chemotherapy had already been administered before surgery to reduce tumor volume. Our study is important because it collects data from 11 tertiary hospitals in Spain, and the data are subjected to a statistical technique that reproduces the data that we would find in a prospective study but using retrospective data (propensity score matching). It also offers a current view of the status of ovarian cancer treatment in our country. Introduction: Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods: A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. Results: A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58–0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64–1.20; p = 0.44). There was no increase in complications in the CRSH group. Conclusion: The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Squamous cell cancer (SCC) of the vulva is one of the rare gynecological malignancies, and surgery is the initial treatment of choice for early-stage vulvar cancer. International guidelines offer conflicting recommendations regarding surgical and pathological tumor-free resection margins for SCC of the vulva. The aim of this study was therefore to analyze the node-negative patients with SCC of the vulva treated with surgery alone at the Department of Women's Health, University Clinic, Tuebingen, Germany with regard to the achieved marginal distance and its impact on prognosis. The present study observed no significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva on disease-free and overall survival. Background: The aim of this study was to evaluate the impact of pathological tumor-free margin distance on survival in SCC patients treated with surgery alone. Methods: This retrospective study included 128 patients with node-negative disease that received no adjuvant treatment. Disease-free and overall survival were analyzed according to pathological tumor-free margin distance. Results: The patients were subclassified into three resection margin category groups: "1 to 3 mm" (n = 42), ">3 to 8 mm" (n = 47) or ">8 mm" (n = 39). Thirty-nine of the 128 patients (30.5%) developed recurrent disease. Median follow-up for disease-free survival (DFS) was 6.49 years (95% CI 5.16 years; 7.62 years), and median follow-up for overall survival (OS) was 6.29 years (95% CI 5.45 years; 7.33 years). The 5-year DFS rate was 0.70 (95% CI: 0.62–0.79), and the 5-year OS rate was 0.79 (95% CI: 0.71–0.87). Regarding the survival outcome, there were no independent significant differences in either disease-free survival (DFS) (p = 0.300) or overall survival (p = 1.000) among patients within the three tumor-free resection margin categories. Multivariate analyses did not show any statistically significant association between tumor-free resection margin distance and recurrent disease or death, either when analyzed as a categorical variable or when analyzed as a continuous variable. Conclusion: The present study did not show a significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva (that did not receive adjuvant treatment) on disease-free and overall survival. [ABSTRACT FROM AUTHOR]

Background: Methylation of the p16 promoter resulting in epigenetic gene silencing—known as p16 epimutation—is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-related p16 epimutation in intestinal tumorigenesis. Methods: We established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs: Apc mutation and p16 epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA sequencing (RNA-seq), quantitative PCR, and flow cytometry. We performed single-cell RNA sequencing (scRNA-seq) to characterize tumor-infiltrating immune cells throughout tumor progression. We tested whether anti-PD-L1 immunotherapy affects overall survival of tumor-bearing mice and whether inhibition of both epigenetic regulation and immune checkpoint is more efficacious. Results: Mice carrying combined Apc mutation and p16 epimutation had significantly shortened survival and increased tumor growth compared to those with Apc mutation only. Intriguingly, colon tumors with p16 epimutation exhibited an activated interferon pathway, increased expression of programmed death-ligand 1 (Pdl1), and enhanced infiltration of immune cells. scRNA-seq further revealed the presence of Foxp3+ Tregs and γδT17 cells, which contribute to an immunosuppressive tumor microenvironment (TME). Furthermore, we showed that a combined therapy using an inhibitor of DNA methylation and a PD-L1 immune checkpoint inhibitor is more effective for improving survival in tumor-bearing mice than blockade of either pathway alone. Conclusions: Our study demonstrated that age-dependent p16 epimutation creates a permissive microenvironment for malignant transformation of polyps to colon cancer. Our findings provide a mechanistic rationale for future targeted therapy in patients with p16 epimutation. [ABSTRACT FROM AUTHOR]

The article presents the discussion on the case study of 85-year-old male with three-month history of a worsening rash on his groin and pubis. Topics include past medical history was remarkable for a remote transitional cell carcinoma of the bladder; and patient was closely monitored with serial imaging and felt to be free of disease once again three months following completion of treatment.

Multiple primary tumors of the parotid gland refer to the occurrence of 2 or more primary tumors in the ipsilateral or bilateral parotid gland metachronously or synchronously, which do not originate from postoperative recurrence or metastasis. Multiple primary tumors of the parotid gland, especially synchronous benign and malignant tumors, are extremely uncommon. A rare case of multiple Warthin tumors with epithelial–myoepithelial carcinoma of the ipsilateral parotid gland is reported as follows. [ABSTRACT FROM AUTHOR]

Background: Methylation of the p16 promoter resulting in epigenetic gene silencing—known as p16 epimutation—is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-related p16 epimutation in intestinal tumorigenesis. Methods: We established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs: Apc mutation and p16 epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA sequencing (RNA-seq), quantitative PCR, and flow cytometry. We performed single-cell RNA sequencing (scRNA-seq) to characterize tumor-infiltrating immune cells throughout tumor progression. We tested whether anti-PD-L1 immunotherapy affects overall survival of tumor-bearing mice and whether inhibition of both epigenetic regulation and immune checkpoint is more efficacious. Results: Mice carrying combined Apc mutation and p16 epimutation had significantly shortened survival and increased tumor growth compared to those with Apc mutation only. Intriguingly, colon tumors with p16 epimutation exhibited an activated interferon pathway, increased expression of programmed death-ligand 1 (Pdl1), and enhanced infiltration of immune cells. scRNA-seq further revealed the presence of Foxp3+ Tregs and γδT17 cells, which contribute to an immunosuppressive tumor microenvironment (TME). Furthermore, we showed that a combined therapy using an inhibitor of DNA methylation and a PD-L1 immune checkpoint inhibitor is more effective for improving survival in tumor-bearing mice than blockade of either pathway alone. Conclusions: Our study demonstrated that age-dependent p16 epimutation creates a permissive microenvironment for malignant transformation of polyps to colon cancer. Our findings provide a mechanistic rationale for future targeted therapy in patients with p16 epimutation. [ABSTRACT FROM AUTHOR]