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Ovarian serous cystadenofibroma is a relatively rare subtype of serous cystadenoma classified as ovarian benign epithelial tumor. We report a rare case of ovarian serous cystadenofibroma with scattered lesions in pelvic cavity, like malignant disseminations. The patient was 22 years old, gravida 0, para 0. In the laparoscopic surgery, numerous hard yellowish‐white solid masses of various sizes were present in the bilateral ovaries. Grossly similar masses were scattered in the fimbria of the fallopian tubes, peritoneum, and great omentum. Because the intraoperative rapid histological diagnosis was benign tumor, surgery was completed for only tumor excision. Postoperative histopathological diagnosis is serous cystadenofibroma. Similar pathological findings were noted in the scattered lesions in the peritoneum and great omentum. No malignant or borderline malignant finding was observed. Because of a benign disease, careful treatment taking fertility preservation into consideration is necessary, especially for young patients. [ABSTRACT FROM AUTHOR]

What is known and objective: Cisplatin‐based chemotherapy is a first‐line treatment for advanced or metastatic urinary tract urothelial carcinoma (UC). Accurate assessment of renal function is indispensable for determining cisplatin dosing to enhance the safety and effectiveness of cisplatin. The objective of this study was to assess serum cystatin C (sCys C) levels in patients with urothelial carcinoma and to explore its clinical value as a serum marker of glomerular filtration rate (GFR). Methods: This study retrospectively enrolled 18 UC patients treated with a combination of gemcitabine and cisplatin between April 2018 and November 2020. We calculated the estimated GFR (eGFR) based on serum creatinine (sCr) or sCys C and estimated Cr clearance (eCCr) based on sCr. The correlation, bias, accuracy and creatinine height index between eGFR or eCCr and measured GFR (mGFR) based on Cr clearance were calculated from urinary Cr and sCr. Results and Discussion: Estimated GFR based on sCys C correlated most strongly with mGFR. Moreover, the bias, mean error, mean absolute error and root mean square error were significantly lower in eGFRs based on sCyc C than in eGFRs based on sCr and eCCr. The correlation between eGFR based on sCys C/mGFR and creatinine height index was weaker than that between eGFR based on sCr/mGFR and creatinine height index, suggesting that sCys C was less affected by muscle mass. What is new and conclusion: In UC patients, eGFR based on sCys C reflected renal function more accurately than eGFR based on sCr, suggesting that sCys C may be useful for assessing renal function in clinical practice. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is a human herpesvirus that causes infectious mononucleosis and contributes to both B-cell and epithelial-cell malignancies. EBV-infected epithelial cell tumors, including nasopharyngeal carcinoma (NPC), are largely composed of latently infected cells, but the mechanism(s) maintaining viral latency are poorly understood. Expression of the EBV BZLF1 (Z) and BRLF1 (R) encoded immediate-early (IE) proteins induces lytic infection, and these IE proteins activate each other's promoters. ΔNp63α (a p53 family member) is required for proliferation and survival of basal epithelial cells and is over-expressed in NPC tumors. Here we show that ΔNp63α promotes EBV latency by inhibiting activation of the BZLF1 IE promoter (Zp). Furthermore, we find that another p63 gene splice variant, TAp63α, which is expressed in some Burkitt and diffuse large B cell lymphomas, also represses EBV lytic reactivation. We demonstrate that ΔNp63α inhibits the Zp promoter indirectly by preventing the ability of other transcription factors, including the viral IE R protein and the cellular KLF4 protein, to activate Zp. Mechanistically, we show that ΔNp63α promotes viral latency in undifferentiated epithelial cells both by enhancing expression of a known Zp repressor protein, c-myc, and by decreasing cellular p38 kinase activity. Furthermore, we find that the ability of cis-platinum chemotherapy to degrade ΔNp63α contributes to the lytic-inducing effect of this agent in EBV-infected epithelial cells. Together these findings demonstrate that the loss of ΔNp63α expression, in conjunction with enhanced expression of differentiation-dependent transcription factors such as BLIMP1 and KLF4, induces lytic EBV reactivation during normal epithelial cell differentiation. Conversely, expression of ΔNp63α in undifferentiated nasopharyngeal carcinoma cells and TAp63α in Burkitt lymphoma promotes EBV latency in these malignancies. Author summary: Epstein-Barr virus (EBV) is an important cause of both epithelial cell and B cell human cancers. EBV-infected tumors have predominantly latent viral infection, allowing them to escape the cell killing that occurs during lytic viral infection. EBV is highly lytic in normal differentiated oral epithelial cells. Thus, an important question is how the virus maintains the latent form of viral infection in EBV-associated epithelial cell tumors such as undifferentiated nasopharyngeal carcinoma (NPC). This study demonstrates that the cellular transcription factor ΔNp63ɑ, which is specifically expressed in undifferentiated basal epithelial cells and is over-expressed in NPC tumors, maintains EBV latency by inhibiting the activity of the viral immediate-early (IE) promoter (Zp) that drives expression of the BZLF1 IE protein. A related splice variant, TAp63α, found in some EBV+ lymphomas, has a similar inhibitory effect. Our findings reveal that ΔNp63ɑ and TAp63α contribute to EBV latency in both epithelial and B cell tumors. Furthermore, since differentiation results in loss of ΔNp63ɑ expression, our results help to explain why lytic EBV reactivation is promoted by epithelial cell differentiation. [ABSTRACT FROM AUTHOR]

Lymphoepithelial carcinoma (LEC) of the salivary gland is a rare malignancy which is identical to undifferentiated nasopharyngeal carcinoma. However, most patients are treated with surgery as primary treatment, which is impossible for some very locoregionally advanced patients. And there are few reports of patients treated by an induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) approach. This report describes 3 cases of advanced stage LEC of the salivary gland. All patients presented with a palpable mass of variable duration and underwent induction CCRT. All cases were positive for Epstein-Barr virus–encoded small RNAs. After IC, all cases had reached partial response and all achieved complete response after CCRT. All patients remained local–regional recurrence-free after 6-month follow-up for case 1, 50-month for case 2, and 14-month for case 3 up to our last follow-up. No serious adverse events were found. [ABSTRACT FROM AUTHOR]

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1 vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions. [ABSTRACT FROM AUTHOR]

The authors comment on the evolving management of epithelioid sarcoma (ES), an aggressive malignant soft-tissue tumor. Topics covered include the approval of the EZH2 inhibitor azemetostat as an ES treatment, results of studies on other treatment options for locally advanced or metastatic ES such as pazopanib and vinorelbine, and a number of promising therapeutic targets in ES.

Glandular metastases (GM) have been associated with improved survival in metastatic clear cell renal cell carcinoma (m-ccRCC). We aimed to molecularly characterize m-ccRCC with GM. We performed a retrospective cohort study on all m-ccRCC patients with available tissue at our institution, diagnosed with metastatic disease from 2000 to 2019. We determined previously described angiogenesis- and immune-related gene expression signatures (GES) and ccrcc molecular subtypes through whole transcriptome RNA sequencing of primary tumors and metastases. We tested differences in GES and molecular subtypes across groups and studied overall (OS) and progression-free survival (PFS) using Kaplan–Meier survival analysis and Cox regression models. Primary tumors of patients who developed GM (n = 55) had higher IMmotion Angio (p < 0.001) and JAVELIN Angio (p = 0.003) GES as well as a higher proportion of angiogenic ccrcc2 molecular subtypes (p = 0.008) than primary tumors of patients with non-GM (n = 128). Metastatic lesions in glandular organs (n = 32) also had higher IMmotion Angio (p = 0.008) and JAVELIN Angio (p = 0.02) GES and were more frequently of the ccrcc2 molecular subtype (p = 0.03), compared to metastatic lesions in non-glandular organs in patients who did not develop any GM (n = 231), but not compared to metastatic lesions in non-glandular organs in patients who also developed GM (n = 18). Patients with GM had better OS (HR 0.49, p < 0.001) and PFS on first-line vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (HR 0.64, p = 0.045) than patients with non-GM. PFS on first- or any-line immuno-oncology (IO) was not different. IMmotion Angio, JAVELIN Angio GES, and ccrcc2 molecular subtype were associated with better OS and PFS on first-line VEGFR-TKIs, but not PFS on first or any-line IO. Patients with m-ccRCC who develop GM are molecularly characterized by heightened angiogenesis, translating into better prognosis and better outcomes on VEGFR-TKIs, but not IO. Based on these findings, VEGFR-TKIs should be included in the first-line treatment of m-ccRCC patients with GM. [ABSTRACT FROM AUTHOR]

Yolk sac tumors (YST) (or endodermal sinus tumors) are rare neoplasms of germ cell origin that have been reported in gonadal sites (testis and ovary). Extragonadal YST are uncommon and are extremely rare in the extracranial head-and-neck regions. Here, we present a rare case of a 1-year-old male with isolated YST of the right parotid gland initially diagnosed as malignant epithelial neoplasm with possibilities of mucoepidermoid carcinoma and epithelial–myoepithelial carcinoma. [ABSTRACT FROM AUTHOR]

Intestinal diffuse ganglioneuromatosis is a rare, benign, neoplastic condition characterized by disseminated proliferation of neural elements. It has an established association with several systemic disorders including: multiple endocrine neoplasia IIB (MEN IIB) and von Recklinghausen's disease. However, isolated GNs are very rare and sporadic. We report a case of a 6-year-old patient was referred to the emergency department due to a colon perforation during endoscopy. He then underwent sigmoidectomy and the pathologic studies revealed prominent signs of diffuse ganglioneuromatosis. Unfortunately, the patient died the day after because of the late diagnosis and treatment. Such presentation emphasizes the importance of considering diffuse ganglioneuromatosis, among other causes, in patients with intractable GI symptoms despite medical treatment. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiotherapy (CCRT) with tri-weekly high-dose cisplatin (HDC) is considered the standard regimen. However, due to significant toxicity, various weekly low-dose schedules have been increasingly used. We investigated the tolerability and survival of patients with head and neck squamous cell carcinoma (HNSCC) who underwent CCRT with low-dose weekly cisplatin (LDC) for Japanese population. Methods: A retrospective review was conducted among patients with HNSCC who were treated with CCRT/LDC in our institute. Ninety-five patients who met the criteria were enrolled in this study. We evaluated the cycle and cumulative cisplatin dose, completion rate of radiotherapy, adverse events, and survival outcome. Results: The mean cycles and cumulative cisplatin dose were 4.7 cycles and 187 mg/m2. All patients completed planned dose of radiation without prolonged breaks. Leucopoenia was the most frequent dose-limiting factor and 44% patients developed grade 3 or 4 toxicity. The 2-year overall survival and recurrence-free survival were 93% and 74%, respectively. The significant differences of survival outcomes between the patients with total cisplatin dose (⩾200 mg and <200 mg) or among age distribution (35-55, 56-75, and ⩾76) were not observed. Conclusions: Concurrent chemoradiotherapy/LDC can be safely administered with acceptable toxicity and survival outcome even if the patients with higher age, lower eGFR, and so on. [ABSTRACT FROM AUTHOR]

Background: Metastatic and unresectable thymoma (T) or thymic carcinoma (TC) have limited treatment options, especially after first line. Methods: Patients with unresectable or recurrent thymic tumors who used minimum one dose of nivolumab at any line of treatment were evaluated retrospectively. Even though nivolumab was administered 3mg/kg dosage in PRIMER study, due to toxicity and financial concerns, we used low dose regimen mostly. Results: Among 46 unresectable and recurrent thymic epithelial tumors; 8 patients with TC (n = 3), T (n = 4) and mixt histology (n = 1) were reviewed. Three patients had myasthenia gravis history that had to be controlled before treatment. Four patients showed moderate (n = 2) or severe (n = 2) adverse events with nivolumab treatment. Interestingly, two severe adverse events were occurred at first dose even with 40 mg nivolumab and required cessation of treatment permanently. The median number of nivolumab received was four (range: 1–18). Best response was partial response. Two patients progressed at the 3rd and 5th month of treatment. Best duration of response for one patient with TC and one patient with T–B2 were 9 and 14 months, respectively. Median survival time after nivolumab was 7.4 months (range: 2–22.1). Conclusions: After the results of the previous study could be supported by randomized prospective studies with more number of patients, nivolumab may be considered as an option in patients with thymic epithelial tumors who have received multiple line treatments. However, given the high rate of severe toxicities, there is need to find out a reliable marker to prediction patients who will derive benefit or exhibit toxicity. [ABSTRACT FROM AUTHOR]

Objective: This study was aimed to analyze the role of T‐cell immunoreceptor with immunoglobulin and tyrosine‐based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC). Materials and Methods: Peripheral blood mononuclear cells (PBMC) and tumor‐infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features was analyzed by chi‐square test. Phenotypic and functional study of TIGIT+ T cells were performed by flow cytometry. Results: TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4+ T cells (19.0%) and CD8+ T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT+CD4+ and TIGIT+CD8+ T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL‐2, TNF‐α and IFN‐γ), and TIGIT+CD4+ T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL‐10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL‐2, TNF‐α, and IFN‐γ) of CD4+ and CD8+ T cells from OSCC patients in vitro. Conclusions: TIGIT‐expressing T cells exhibit a lower effector cytokine‐releasing phenotype in OSCC patients. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a survival rate of less than 7%, mainly due to the hepatic metastatic spread. Despite the importance of understanding PDAC metastases, central questions remain concerning their biology and chemosensitivity. Moreover, the transcriptomic divergence between primary tumor (PT) and hepatic metastases (HM) has been poorly studied and without a clear dissection of the confounding tumoral-surrounding tissue. Here, to unravel key biological features not biased by the surrounding tissue, we implemented a blind source separation based on independent component analysis, ProDenICA, on a treatment-naïve cohort of PDAC paired samples and a cohort of 305 resectable patients. In addition, a time-lapse experiment was performed to assess the gemcitabine chemosensitivity profile between the PT and HM. We identified HM's specific transcriptomic characteristics related to the upregulation of cell cycle checkpoint, mitochondria activity, and extracellular matrix reorganization, which could be associated with metastatic niche adaptation mechanisms. Furthermore, squamous lineage emerged as a key feature linked with a downregulation in the epithelial-to-mesenchymal program that can stratifies PDAC HM independent of the classical/basal-like spectrum. Remarkably, we also demonstrated that gemcitabine response is influenced by the squamous profile, being the HM more refractory to the treatment than the PT. These results pointed out divergent HM aspects compared to PT and allowed their stratification through the squamous lineage. Moreover, we unravel a clinical actionable squamous signature that predicts the gemcitabine response. • The squamous lineage has been related to a high aggressiveness and poor prognosis. • Squamousness stratifies PDAC independent of classical/basal-like phenotype. • Hepatic metastases displayed a higher squamous profile than the primary tumor. • The squamousness level predicts patients' adjuvant gemcitabine response. [ABSTRACT FROM AUTHOR]

Adenosquamous carcinoma of the head and neck is a rare cancer associated with poor prognosis. Histologically, it is identified through the presence of both adenocarcinoma and squamous cell carcinoma, although it may be difficult to diagnose from initial endoscopic biopsies. We report a case of adenosquamous carcinoma of the glottis in an 82-year-old female patient who presented with progressive hoarseness of voice and in whom initial biopsies had shown only moderate to severe dysplasia. This is the first case in the literature of a primary adenosquamous carcinoma of the glottis managed successfully with a CO2 laser left type Va cordectomy. The patient remained disease-free 28 months postoperatively. [ABSTRACT FROM AUTHOR]

Lung cancers with anaplastic lymphoma kinase (ALK) rearrangements are highly sensitive to treatment with ALK tyrosine kinase inhibitors (TKIs). Due to the very low rate of patients with squamous cell carcinoma enrolled in clinical trials, the efficacy of ALK inhibitors in patients with ALK‐rearranged squamous cell carcinoma in the lung remains unclear. Herein, we present the case of a 70‐year‐old female patient with squamous cell lung cancer harboring the echinoderm microtubule‐associated protein‐like 4 (EML4)‐ALK fusion gene. The patient was treated with the ALK‐TKI alectinib as first‐line regimen and achieved a dramatic response without severe adverse events, demonstrating alectinib as a therapeutic option for patients with ALK‐positive squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression‐free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score. Methods: This was a post hoc analysis of a multicenter, double‐blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively. Results: The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI: 3.5–11.0) versus 3.2 (95% CI: 1.2–5.3) months, p = 0.001; HR (95% CI), 0.4 (0.2–0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI: 3.0–11.0) vs. 4.8 (95% CI: 1.2–8.5) months (p = 0.043). No statistically significant differences were found in OS in the stratified analyses. Conclusions: The occurrence of hypertension might be a clinical indicator predicting the efficacy of third‐line anlotinib treatment in patients with SCC. [ABSTRACT FROM AUTHOR]

Purpose: In addition to histology, genetic alteration is now required to classify many central nervous system (CNS) tumors according to the most recent World Health Organization CNS tumor classification scheme. Although that is still not the case for classifying pediatric low-grade neuroepithelial tumors (PLGNTs), genetic and molecular features are increasingly being used for making treatment decisions. This approach has become a standard clinical practice in many specialized pediatric cancer centers and will likely be more widely practiced in the near future. This paradigm shift in the management of PLGNTs necessitates better understanding of how genetic alterations influence histology and imaging characteristics of individual PLGNT phenotypes. Methods: The complex association of genetic alterations with histology, clinical, and imaging of each phenotype of the extremely heterogeneous PLGNT family has been addressed in a holistic approach in this up-to-date review article. A new imaging stratification scheme has been proposed based on tumor morphology, location, histology, and genetics. Imaging characteristics of each PLGNT entity are also depicted in light of histology and genetics. Conclusion: This article reviews the association of specific genetic alteration with location, histology, imaging, and prognosis of a specific tumor of the PLGNT family and how that information can be used for better imaging of these tumors. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell cancer (HNSCC) involves cancer of the oral cavity, oropharynx, hypopharynx and larynx. By virtue of the tumour location, nutrition support in this patient cohort can be extremely challenging. A 48-year-old male presented with a two-month history of progressive dysphagia, significant loss of weight, shortness of breath and coughing secondary to a non-benign lesion in his throat. This debilitating condition led to severe malnutrition and due to the prevailing nutritional risk the patient was assessed as a very high risk for refeeding syndrome. Several investigations were done during the admission, which then confirmed the final diagnosis of a transglottic squamous cell cancer. Surgical optimisation, including preoperative nutritional optimisation, was discussed in a multidisciplinary meeting and a total laryngectomy was scheduled seven days later. Perioperative nutritional management required careful consideration of several factors but the involvement of dietetics services from the day of admission played a crucial role in the successful management of this patient. [ABSTRACT FROM AUTHOR]

We encountered a case of spontaneous thymic carcinosarcoma in a young Crl:CD (Sprague Dawley) rat. Grossly, a white multinodular mass replaced the thymus in the thoracic cavity. Histologically, multiple nodules were separated by fibrous stroma, and each nodule included isolated regions that were composed of epithelial or non-epithelial tumor cells. The epithelial tumor cells were relatively large and round to polygonal cells with large nuclei and weakly eosinophilic cytoplasm. These cells were cytokeratin-positive and vimentin-negative. These cells infiltrated the lungs. The non-epithelial tumor cells were poorly differentiated, small, round to spindle-shaped cells with small nuclei and basophilic cytoplasm. These cells were vimentin-positive and mostly cytokeratin-negative. Many islands of cartilage were observed near non-epithelial cells. Based on these findings, the tumor was diagnosed as a primary thymic carcinosarcoma consisting of a malignant thymoma composed of epithelial tumor cells and a mesenchymal chondrosarcoma composed of non-epithelial tumor cells. [ABSTRACT FROM AUTHOR]

As several multi‐target drug delivery approaches are successfully identified through preclinical screening, their clinical success is often hampered by challenges such as poor circulation stability, dissimilarities in the pharmacokinetics of different drugs, as well as targeting inefficiency. Gold nanoparticles (AuNPs) are adopted as promising nanocarriers in the co‐delivery of multiple therapeutic drugs for combination therapy. The pH‐responsive AuNPs are synthesized and incorporated with multiple chemotherapeutic drugs, such as doxorubicin and bleomycin. Such structures can work as drug carriers to treat cervical carcinoma by adopting a quality by design approach. The designed nanocarrier is characterized by adopting a range of physicochemical and morphological techniques. In vitro drug release and cytotoxicity of optimized nanocarriers are assessed to cervical tumor epithelial cells. The results highlight the notable advantages of colloidal AuNPs, including sustained drug release, therapeutic agent delivery with high stability, and biocompatibility for more effective treatment of cervical carcinoma. Furthermore, by improving the biodistribution and/or bioavailability profiles, it is believed that the two‐in‐one approach may therefore give evidence on the fate of co‐loaded nanocarrier as a promising trajectory for successful clinical translation against ovarian carcinoma to achieve maximum therapeutic synergy for an individual patient. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the anus (SCCA) is a rare malignancy with rising incidence, associated with human papilloma virus (HPV). Chemoradiotherapy (CRT) is the preferred treatment. The purpose was to investigate treatment failure, survival and prognostic factors after CRT. In this prospective observational study from a large regional centre, 141 patients were included from 2013 to 2017, and 132 were eligible for analysis. The main inclusion criteria were SCCA, planned radiotherapy, and performance status (ECOG) ≤2. Patient characteristics, disease stage, treatment, and treatment response were prospectively registered. Disease-free survival (DFS), overall survival (OS), and locoregional treatment failure after CRT were analysed. Hazard ratios (HRs) were estimated with Cox's proportional hazards model. Median follow-up was 54 (range 6–71) months. Eighteen patients (14%) had treatment failures after CRT; of these 10 (8%) had residual tumour, and 8 (6%) relapse as first failure. The first treatment failure was locoregional (11 patients), distant (5 patients), and both (2 patients). Salvage abdomino-perineal resection was performed in 10 patients, 2 had resections of metastases, and 3 both. DFS was 85% at 3 years and 78% at 5 years. OS was 93% at 3 years and 86% at 5 years. In analyses adjusted for age and gender, HPV negative tumours (HR 2.5, p = 0.024), N3 disease (HR 2.6, p = 0.024), and tumour size ≥4 cm (HR 2.4, p = 0.038) were negative prognostic factors for DFS. State-of-the-art chemoradiotherapy for SCCA resulted in excellent outcomes, and improved survival compared with previous national data, with <15% treatment failures and a 3-year DFS of >80%. [ABSTRACT FROM AUTHOR]

Hepatoid adenocarcinoma is a poorly differentiated alpha-fetoprotein-producing (AFP) tumor frequently located in the stomach, ovary, and pancreas. Presentation in the stomach has a high mortality rate due to late diagnosis, which offers the patient few therapeutic alternatives. On February 22, 2019, a 44-year-old woman from Lima entered the emergency department for pain in the right hypochondrium for 4 months, weight loss, nausea, and asthenia. On physical examination, hepatomegaly presented with a liver spam of 17 cm. Serology showed severe anemia and AFP of 49,800. The tomography showed multiple hypodense lesions in the liver and the presence of nodes. Endoscopy showed Bormann III gastric malignancy. Gastric biopsy determined undifferentiated epithelial malignancy; the immunohistochemical mark (+) for AFP and PAS Diastase confirmed a hepatoid gastric adenocarcinoma. A rare variant of gastric adenocarcinoma was evident, which often mimics an HCC. In this case, multiple liver metastases were observed that differed from the diagnosis of HCC, so this variant must always be taken into account when a primary gastric tumor presents with hepatic metastases. [ABSTRACT FROM AUTHOR]

Introduction: Dysembryoplastic neuroepithelial tumor (DNT) is a rare benign brain tumor predominantly involving children and young adults. Histologically, it corresponds to WHO Grade I tumors; however, it may masquerade aggressive neural tumors such as oligodendroglioma, oligoastrocytoma, pilocytic astrocytoma, and ganglioglioma. The literature on clinical, radiological, and pathological spectrum of DNT is described mostly in the form of case reports, with only a few case series reported till date.Methods: A retrospective review of files with diagnosis of DNT (2016 to 2018) was made in the Department of Pathology, National Institute of Pathology, New Delhi. A total of ten cases were retrieved, and their clinical, radiological, and histopathological features were reviewed and studied. Special stains and immunohistochemistry were done, wherever required.Results: The mean age was 14.8 (±7.9) years, with a male-to-female ratio of 1.5:1. The most common mode of presentation was recurrent, intractable seizures. The most common site of lesion was parietal lobe followed by temporal and frontal lobes of the brain. On histology, mucoid matrix admixed with floating neurons and oligodendrocyte-like cells was a consistent feature; however, the presence of specific glioneuronal elements was observed in only a few cases.Conclusions: DNT is a benign, low-grade, nonrecurrent neuroepithelial neoplasm. It is important to differentiate this rare entity from other mimickers, as it is surgically curable and carries an excellent prognosis without the need for adjuvant chemotherapy and radiotherapy. The study helps to enrich the clinicopathological aspects of this rare but important entity. [ABSTRACT FROM AUTHOR]

A large tumorous mass completely surrounding and compressing the coeliac trunk was identified on computed tomography in a young woman with a six-month history of progressive abdominal pain. The tumor was excised along with the coeliac trunk and the proximal parts of its branches. The hepatic artery was reconstructed with an aorto-hepatic autogenous bypass. Postoperatively the patient had neurogenic diarrhea, which subsided on medical treatment. Seven months after surgery the patient is in a good state of health and living a normal life. [ABSTRACT FROM AUTHOR]

Background: NUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. NC is largely chemoresistant, with an overall survival of less than 7 months. Because the carcinoma is not restricted to a particular organ, diagnosis is often a challenge. In the absence of a clearly determined incidence for NC, we sought to study the diagnosis of patients in a well-defined population.Methods: We systematically reviewed records of all patients that presented to the Oncology Department of the Princess Margaret Hospital for Children from 1989 to 2014. This institution in the geographically isolated state of Western Australia has a catchment population of around 2 million. We then identified all high grade undifferentiated sarcomas or carcinomas in the 0-16 year age group.Results: Over 26 years, we found 14 patients of 16 years or younger with undifferentiated malignant tumors. Of these, five tumors were positive by immunohistochemistry for the NUT/NUTM1 (Nuclear Protein in Testis) protein and/or the translocation t(15;19). Three patients presented with thoracic tumors, one with a para-spinal tumor, and one had an upper airway nasopharyngeal carcinoma. In all five cases, there was an initial response to therapy and then progression. This 26-year survey was conducted in a geographically isolated state with a well-defined population, and we determined an estimated incidence of NC of around 0.41 per million child years (0-16 yrs. of age) at risk. From three patients it was feasible to derive cell lines for further genetic analyses and drug screening.Conclusions: For the first time, the incidence of NC could be determined in a well-defined geographic area. The calculated rate of NC incidence is consistent with a history of under-recognition for this malignancy. These findings indicate that improved diagnostic detection of NC would enable better management and counselling of patients. Our findings emphasize the heterogeneity of NC, and they highlight the need to develop personalised therapy options, and to consider a diagnosis of NC in undifferentiated malignant tumors. [ABSTRACT FROM AUTHOR]

Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings. We conducted a 36-centre, retrospective cohort study in patients with chemo-naïve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019. The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9–16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6–6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4–10.5) and 9 patients (3.0%, 95% CI 1.4–5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0–6.8) and 7.5 (95% CI 6.5–8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07–3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12–8.20, P = 0.03). Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy. UMIN000038084 • Data on pembrolizumab plus chemotherapy-induced pneumonitis are limited. • We conducted a 36-centre, retrospective cohort study. • Treatment-related pneumonitis occurred at a higher rate in real-world settings. • After adjusting for immortal time bias, pneumonitis led to worse survival outcomes. • Our findings indicate that pneumonitis requires the careful attention of clinicians. [ABSTRACT FROM AUTHOR]

Years of investigation have shed light on a theory in which breast tumor epithelial cells are under the effect of the stromal microenvironment. This review aims to discuss recent findings concerning the phenotypic and functional characteristics of cancer associated fibroblasts (CAFs) and their involvement in tumor evolution, as well as their potential implications for anti-cancer therapy. In this manuscript, we reviewed that CAFs play a fundamental role in initiation, growth, invasion, and metastasis of breast cancer, and also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of this disease. [ABSTRACT FROM AUTHOR]

Backgroud: Recent studies have indicated that programmed cell death‐ligand 1 (PD‐L1) and cluster of differentiation 47 (CD47) play an essential role in tumor immune evasion and may serve as potential targets for combined immunotherapy. The aim of our study was to evaluate the PD‐L1/CD47 expression status in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), and explore its survival impact and relevance with the immune microenvironment. Methods: The specimens from 190 LUSC and 240 LUAD patients who underwent intent‐to‐treat surgeries were retrospectively collected for immunohistochemistry assays of PD‐L1, CD47, cluster of differentiation 8 (CD8), and cluster of differentiation 68 (CD68). Results: A total of 96 (22.3%) and 296 (68.8%) cases were positive for PD‐L1 and CD47 expression, respectively, and 80 (18.6%) of them demonstrated the co‐expression of PD‐L1/CD47. The rate of PD‐L1/CD47 co‐expression was 23.7% in LUSC, significantly higher than the 14.6% in LUAD (p = 0.018). The median overall survival (OS) for all patients was 55.9 months (range 2.0–146.0 months). The univariate analysis showed that patients with positive CD47 expression (LUSC p = 0.003, LUAD p = 0.036) and PD‐L1/CD47 co‐expression (LUSC p = 0.023, LUAD p = 0.004) exhibited significantly worse prognosis. The multivariate analysis demonstrated that PD‐L1/CD47 co‐expression was an independent prognostic factor for OS (LUSC hazard ratio [HR] 1.922, 95% CI 1.245–2.969, p = 0.003; LUAD HR 1.549, 95% CI 1.015–2.364, p = 0.043). PD‐L1/CD47 co‐expression was associated with high CD8‐positive T‐lymphocyte density in LUSC (p = 0.004) and LUAD (p = 0.043), and with high CD68‐positive macrophage density in LUSC (p = 0.026). Conclusions: PD‐L1/CD47 co‐expression was an independent prognostic factor for LUSC and LUAD patients and may serve as a potential predictive biomarker for combined dual‐targeting immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle depletion (sarcopenia) is associated with poor prognosis in patients with lung cancer. We analyzed changes in skeletal muscle area using serial computed tomography (CT) until the death of patients with advanced squamous cell lung cancer (SQCLC). Methods: This retrospective study comprised 70 consecutive patients who underwent palliative chemotherapy for SQCLC. The cross‐sectional area of the skeletal muscle at the level of the first lumbar vertebra (L1) was measured using chest CT. An artificial intelligence algorithm was developed and used for the serial assessment of the muscle area. Sarcopenia was defined as an L1 skeletal muscle index <46 cm2/m2 in men and < 29 cm2/m2 in women. Results: The median age was 69 years; 62 patients (89%) had metastatic disease at the time of initial diagnosis. Sarcopenia was present in 58 patients (82.9%) at baseline; all patients experienced net muscle loss over the disease trajectory. The median overall survival was 8.7 (95% confidence interval 5.9–11.5) months. The mean percentage loss of skeletal muscle between the first and last CT was 16.5 ± 11.0%. Skeletal muscle loss accelerated over time and was the highest in the last 3 months of life (p < 0.001). Patients losing skeletal muscle rapidly (upper tertile, >3.24 cm2/month) had shorter overall survival than patients losing skeletal muscle slowly (median, 5.7 vs. 12.0 months, p < 0.001). Conclusions: Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life. Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life. [ABSTRACT FROM AUTHOR]

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC. [ABSTRACT FROM AUTHOR]

Collective cell migration of epithelial tumor cells is one of the important factors for elucidating cancer metastasis and developing novel drugs for cancer treatment. Especially, new roles of E-cadherin in cancer migration and metastasis, beyond the epithelial-mesenchymal transition, have recently been unveiled. Here, we quantitatively examined cell motility using micropatterned free edge migration model with E-cadherin re-expressing EC96 cells derived from adenocarcinoma gastric (AGS) cell line. EC96 cells showed increased migration features such as the expansion of cell islands and straightforward movement compared to AGS cells. The function of tight junction proteins known to E-cadherin expression were evaluated for cell migration by knockdown using sh-RNA. Cell migration and straight movement of EC96 cells were reduced by knockdown of ZO-1 and claudin-7, to a lesser degree. Analysis of the migratory activity of boundary cells and inner cells shows that EC96 cell migration was primarily conducted by boundary cells, similar to leader cells in collective migration. Immunofluorescence analysis showed that tight junctions (TJs) of EC96 cells might play important roles in intracellular communication among boundary cells. ZO-1 is localized to the base of protruding lamellipodia and cell contact sites at the rear of cells, indicating that ZO-1 might be important for the interaction between traction and tensile forces. Overall, dynamic regulation of E-cadherin expression and localization by interaction with ZO-1 protein is one of the targets for elucidating the mechanism of collective migration of cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: BRAF p.V600E is reported in up to 80% of ameloblastomas. Despite the high frequency, the presence of this mutation in different histopathological areas of the tumour has not been investigated. This information has an important role in the use of BRAF p.V600E assessment as an auxiliary tool in the differential diagnosis between unicystic ameloblastoma and other odontogenic cystic lesions, especially when only incisional biopsies are available. Therefore, the purpose of the present study was to investigate BRAF p.V600E heterogeneity in unicystic ameloblastoma. Methods: Five cases of ameloblastoma and two dentigerous cysts were analysed. The regions exhibiting different microscopic characteristics were selected from each ameloblastoma case and manually dissected. TaqMan allele‐specific qPCR or Sanger sequencing was performed to determine BRAF p.V600E status. Results: We screened the mutation in a small cohort of UA and no molecular heterogeneity was found. Four cases of ameloblastoma (80%) exhibited BRAF p.V600E in all different areas evaluated. One case did not harbour the mutation in any microscopic region analysed. The BRAF mutation was absent in the dentigerous cysts. Conclusion: Ameloblastomas appear to exhibit a homogeneous profile regarding the BRAF p.V600E no matter what histological feature is observed under light microscopy, suggesting that this molecular test may contribute to establish the correct diagnosis in cases microscopically resembling other odontogenic lesions. [ABSTRACT FROM AUTHOR]

Afatinib is an ErbB family blocker approved for the treatment of epidermal growth factor receptor mutation‐positive nonsmall‐cell lung cancer. A pivotal trial demonstrated significant clinical benefits with manageable toxicity of afatinib as a second‐line treatment option in squamous cell carcinoma of the lung (SCC) which led to approval in >60 countries. However, these results were derived from a controlled study conducted in selected patients and are not necessarily representative of the real‐world use of this drug. In addition, data on afatinib use after immunotherapy in this clinical setting are lacking. The aim of this study is to evaluate the treatment outcomes and safety of afatinib as a second‐ or later‐line treatment for SCC and to identify potential predictive biomarkers. As a real‐world observational study, 130 eligible patients with advanced SCC, who progressed after platinum‐based chemo‐ and immunotherapy, will be enrolled. Treatment outcomes and safety data will be collected for both the retrospective and prospective cohorts, and molecular profiling using tissue and plasma will be performed for the prospective cohort. The primary endpoint is time to treatment failure, and the secondary endpoints are objective response rate, progression‐free survival, overall survival, and safety. Comparison of clinical outcomes with respect to the different programmed death‐ligand 1 expression and molecular characteristics will also be carried out. This study will provide additional evidence on the usefulness of afatinib as a subsequent treatment, as well as feasible molecular biomarkers to predict its efficacy in this clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: Gliomatosis cerebri (GC) is defined by diffuse, widespread glial tumor growth affecting three or more cerebral lobes. Previous studies in gliomas found no distinct histological or molecular GC subtype, yet the presence of GC is associated with worse median overall survival (OS). Here, we explored whether differing therapeutic strategies in first-line treatment could account for this. Methods: From our University Cancer Center database, 47 patients with histological diagnosis of WHO grade II or III glioma and GC imaging pattern were identified. GC criteria were confirmed by independent review. Patients with WHO grade II or III glioma with non-GC pattern served as control cohort (n = 343). Results: Within the GC patient cohort, lower WHO grade, mutated isocitrate dehydrogenase 1 (IDH1) status, and absence of contrast enhancement were associated with better OS. Compared to the control cohort, patients with GC had significantly shorter OS independent of histological diagnosis or IDH1 mutation status. Patients with GC preferentially received chemotherapy alone (62 vs. 18%), and less frequently radiochemotherapy (21 vs. 27%). OS was significantly shorter in the GC cohort compared to the non-GC cohort both for chemotherapy (3.9 vs. 7.6 years, p = 0.0085) and for combined radiochemotherapy (1.1 vs. 8.4 years, p < 0.0001). However, when only patients who received biopsy plus chemotherapy were analyzed, the differences lost statistical significance (3.5 vs. 6.6 years, p = 0.196). Conclusion: We found major differences in the selection of first-line therapies of GC versus non-GC patients. Our results suggest that these differences may partly account for the worse prognosis of GC patients. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐33 cytokine plays a critical role in allergic diseases and cancer. IL‐33 also has a nuclear localization signal. However, the nuclear function of IL‐33 and its impact on cancer is unknown. Here, we demonstrate that nuclear IL‐33‐mediated activation of SMAD signaling pathway in epithelial cells is essential for cancer development in chronic inflammation. Using RNA and ChIP sequencing, we found that nuclear IL‐33 repressed the expression of an inhibitory SMAD, Smad6, by interacting with its transcription factor, RUNX2. IL‐33 was highly expressed in the skin and pancreatic epithelial cells in chronic inflammation, leading to a markedly repressed Smad6 expression as well as dramatically upregulated p‐SMAD2/3 and p‐SMAD1/5 in the epithelial cells. Blocking TGF‐β/SMAD signaling attenuated the IL‐33‐induced cell proliferation in vitro and inhibited IL‐33‐dependent epidermal hyperplasia and skin cancer development in vivo. IL‐33 and SMAD signaling were upregulated in human skin cancer, pancreatitis, and pancreatitis‐associated pancreatic cancer. Collectively, our findings reveal that nuclear IL‐33/SMAD signaling is a cell‐autonomous tumor‐promoting axis in chronic inflammation, which can be targeted by small‐molecule inhibitors for cancer treatment and prevention. The cell‐autonomous functions of cytokines and their impact on cancer promotion are unclear. Here, we demonstrate that nuclear IL‐33 promotes epithelial carcinogenesis in chronic inflammation independent of its cytokine function. IL‐33 is highly induced and localized in the epithelial cell nuclei of the skin and pancreas affected by chronic inflammation.Nuclear IL‐33 upregulates SMAD signaling in epithelial cells by repressing the expression of Smad6 (an inhibitory SMAD).Nuclear IL‐33 binds to the RUNX2 transcription factor to block Smad6 expression.Nuclear IL‐33 promotes epithelial cell proliferation and tumor development by upregulating SMAD signaling in cancer‐prone chronic inflammation of skin and pancreas. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is a new disease in the World Health Organization's classification of tumors of soft tissue and bone published in 2013. Primary mediastinal UPS is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, which was initially misdiagnosed as epithelial malignant pleural mesothelioma (MPM). The cytopathological findings of the pleural effusion cell block often contribute to the diagnosis of various malignant tumors. However, these findings may lead to misdiagnosis of highly invasive mediastinal tumors such as UPS. A biopsy for primary mediastinal lesions should be performed because MPM rarely mimics mediastinal tumors with pleural effusion. [ABSTRACT FROM AUTHOR]

Background: Intestinal Ganglioneuromatosis (IG) is a rare disorder of the enteric nervous system. In pediatric age it is often associated with genetic syndromes such as Neurofibromatosis 1 (NF1), multiple endocrine neoplasia type 2B (MEN2B) and Cowden syndrome (PTEN mutation), and ganglioneuromas (GNs) may be sometimes the first sign of the disease. Isolated GNs are rare and sporadic. Clinical symptom vary and depend on the size and on the location of the GNs. This disorder affects intestinal motility and it, consequently, causes changes in bowel habits, abdominal pain, occlusive symptoms and rarely lower gastrointestinal bleeding secondary to ulceration of the intestinal mucosa. On the other hand, patients can remain asymptomatic for many years. Case presentation: We describe a 9-year-old boy referred to our emergency department for right lower quadrant abdominal pain. No familial history for gastrointestinal disorders. No history of fever or weight loss. At physical examination, he had diffused abdominal pain. Abdominal ultrasonography showed a hypoechoic formation measuring 41.8 mm by 35 mm in the right lower quadrant of the abdomen. Routine blood tests were normal, but fecal occult blood test was positive. Abdominal TC confirmed the hypodense formation, of about 5 cm in transverse diameter, in the right hypochondrium that apparently invaginated in the caecum-last ileal loop. Colonoscopy showed in the cecum an invaginated polypoid lesion of the terminal ileal loop. Laparoscopic resection of the polypoid lesion was performed. Histological diagnosis of the large neoplasm observed in the terminal ileum was diffuse ganglioneuromatosis. NF1, RET and PTEN gene tests resulted negative for specific mutations. At the 1 year follow-up, the patient presented good general condition and blood tests, fecal occult blood test, esophagogastroduodenoscopy, colonoscopy and MR-enterography were negative. Conclusions: Only few cases are reported in literature of IG in pediatric age. Although rare, the present case suggests that this disorder must be taken in consideration in every patient with GI symptoms such as abdominal pain, constipation, lower intestinal bleeding, in order to avoid a delayed diagnosis. [ABSTRACT FROM AUTHOR]

EPHA2 is a member of the ephrin receptor tyrosine kinase family and is closely related to the malignant tumor progression. The effect of EPHA2 on OSCC is not clear. This study explored the role of EPHA2 and AKT/mTOR signaling pathways in Cal-27 cell invasion and migration. The expression of EPHA2 and EPHA4 in human OSCC and normal oral tissue was detected by immunohistochemistry. EPHA2-overexpressing and EPHA2-knockdown Cal-27 cells were established, and the cells were treated with an AKT inhibitor (MK2206) and mTOR inhibitor (RAD001). The expression of EPHA2 was detected by qRT-PCR, cell proliferation was evaluated by MTT assay, cell migration and invasion were examined by scratch and Transwell assay, and cell morphology and apoptosis were assessed by Hoechst 33258 staining. Western blot was performed to detect the expression of proteins related to AKT/mTOR signaling, cell cycle, and pseudopod invasion. EPHA2 and EPHA4 were highly expressed in clinical human OSCC. Overexpression of EPHA2 promoted the proliferation, migration, and invasion of Cal-27 cells, inhibited cell cycle blockage and apoptosis, and enhanced the activity of the AKT/mTOR signaling pathway. MK2206 (AKT inhibitor) and RAD001 (mTOR inhibitor) reversed the effect of EPHA2 overexpression on the biological behavior of Cal-27 cells. EPHA2 promotes the invasion and migration of Cal-27 human OSCC cells by enhancing the AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective study was to provide additional data on the use of toceranib in a wide variety of tumor types in small breed dogs, especially < 8 kg (except 5 dogs). This was a retrospective study of 31 dogs with malignant tumors treated with a 2.5 mg/kg median dose of toceranib (Palladia; Zoetis, USA) on a Monday– Wednesday–Friday schedule. Clinical benefit was observed in 13 of 15 dogs (86.7%, 3 with complete response, 4 with partial response, 6 with stable disease) with gross disease. Distant metastasis, response to treatment, and treatment setting were significantly associated with survival time. Negative prognostic factors were multiple chemotherapy and distant metastasis (affecting progression-free survival [PFS]), surgery, regional enlarged lymph nodes, underlying disease, and toxicity (affecting median survival time [MST]). Positive prognostic factors were epithelial and round cell tumor (affecting PFS), epithelial tumor, microscopic disease, no evidence of disease response, and stable disease (MST). In conclusion, a clinical benefit from toceranib treatment was noted in most of the dogs with gross disease in our study. This study suggested that the toceranib is probably selective treatment to various tumor types in small breed dogs. [ABSTRACT FROM AUTHOR]

Background: To assess the correlation of WHO histological classification and Masaoka–Koga staging system of thymic epithelial tumors (TETs) with prognosis. Methods: We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka–Koga staging system. Survival curves were constructed with Kaplan‐Meir method. Results: There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III–IV) was high (65%). With a median follow‐up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka–Koga staging had an effect on survival. Conclusions: The results indicates a clear association between the WHO histological classification and Masaoka–Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment. Key points: Significant findings of the study: The WHO histological classification, the Masaoka–Koga system and surgery treatment were associated with overall survival. What this study adds: To determine prognosis factors in TETs. [ABSTRACT FROM AUTHOR]

Objective: To compare the incidence, demographics and clinical outcomes of women presenting with possible non-cervical (NC) and endocervical (EC) glandular neoplasms in their cervical smears.Study Design: Retrospective analysis of a prospective cohort within the NHS Greater Glasgow and Clyde- the largest health organisation in Scotland, UK.Methods: Cases identified from the Scottish Cervical Call Recall System between January 2013 and December 2017. Incidence and clinical trajectories of NC and EC were reviewed.Results: Two-hundred-and-thirty cases (NC = 41; EC = 189) from 486,240 smears were evaluated. The incidence was 8.4 and 38.9 per 100,000 smear-year for NC and EC, respectively. Compared to women with EC, women with NC were significantly older (p < 0.0001), had higher body mass index (p < 0.0001), more likely to present with symptoms (58.5 % vs 10.5 %; p < 0.0001), had cancers (48.8 % vs 13.8 %; p < 0.0001) and died from their diseases (9.8 % vs 0.5 %; p < 0.0001). Even in the asymptomatic screen-detected NC group, almost a quarter (23.5 %) had endometrial cancer. Age was not associated with high-risk histology (p = 0.289). High-risk colposcopic appearance had good positive predictive value (90.0 %; 95 %CI: 81.2-95.6 %) for high-risk histology, but poor negative predictive value (41.3 %; 95 %CI: 29-54 %). Negative excision margin was associated with favourable outcomes.Conclusions: NC and EC are rare, but they are distinct and should be reported separately in future studies. The risks of malignancies are high, particularly in women with NC, even if they are asymptomatic. Thus, prompt and thorough investigations and treatments are required to prevent and treat malignancies. [ABSTRACT FROM AUTHOR]

We compared the clinicopathologic characteristics and prognosis of adenosquamous carcinoma (ASQ) of the breast with invasive ductal carcinoma (IDC), utilizing the National Cancer Database (NCDB) from 2004 to 2015. 1 932 688 female patients had invasive breast carcinoma; 1 421 250 had IDC (73.5%); and 453 had ASQ (0.0002%). When compared to IDC, ASQ patients were significantly (P <.05) older and had grade 1 tumors; negative lymph nodes; ER/PR/HER2‐negative tumors; and worse 5‐year overall survival (64.9% vs 74%, respectively). Our study, largest to date on ASQ, revealed an aggressive carcinoma with a significantly worse prognosis than IDC. "Personalized medicine" treatment approach for patients with this uncommon carcinoma is needed. [ABSTRACT FROM AUTHOR]

Inflammatory Breast Cancer (IBC) is the most aggressive form of breast carcinoma characterized by rapid onset of inflammatory signs and its molecular fingerprint has not yet been elucidated. The objective of this study was to detect both gene expression levels and alternate RNA splice variants specific for IBC. W e performed splice-sensitive array profiling using Affymetrix Exon Array and quantitative RT-PCR analyses in 177 IBC compared to 183 non-IBC. We also assessed the prognostic value of the identified candidate genes and splice variants. A 5-splice signature (HSPA8 , RPL10 , RPL4 , DIDO1 and EVL) was able to distinguish IBC from non-IBC tumors (p<10-7). This splice signature was associated with poor metastasis-free survival in hormone receptor-negative non-IBC (p=0.02), but had no prognostic value in IBC. PAM analysis of dysregulated genes in IBC compared to non-IBC identified a 10-gene signature highly predictive of IBC phenotype and conferring a poor prognosis in non-IBC. The genes most commonly upregulated in IBC were 3 hemoglobin genes able to reliably discriminate IBC from non-IBC (p<10-4). Hb protein expression in epithelial breast tumor cells was confirmed by immunohistochemistry. IBC has a specific spliced transcript profile and is characterized by hemoglobin gene overexpression that should be investigated in further functional studies. [ABSTRACT FROM AUTHOR]

Background: Thymic epithelial tumors constitute a morphologically and clinically diverse group of rare neoplasm of the anterior mediastinum. Methods: Here, we present an analysis of 188 patients diagnosed with primary thymic tumors between 1995 and 2015. The prognostic value of selected clinical and morphological factors was assessed in relation to overall survival and recurrence‐free survival. Results: The risk of recurrence increased significantly in thymic carcinoma diagnosis (P = 0.0036), co‐occurrence of other diseases, and weight loss (P = 0.0012 and 0.0348, respectively). Multivariate analysis showed that the most important independent risk factor for disease recurrence was clinical stage IV (P = 0.0036). A total of 63 patients (33.5%) died. In the univariate analysis, the following factors were considered as independent prognostic factors for overall survival: clinical stage (P < 0.0001), histological type (P < 0.0001), lymph node involvement (P < 0.001), WHO performance status 2 (P < 0.0001), anemia (Hb <9.5 g/dL; P = 0.0002), leucocytosis (>12.5 G/L; P = 0.0011), LDH level (>185 U/L; P < 0.0001), concomitant diseases (P = 0.0012) and weight loss (P < 0.0001).The strongest independent risk factor for death was stage IV disease (P < 0.001). Conclusions: The results confirmed a fairly good prognosis for patients with thymic epithelial tumors. Clinical stage was the most important prognostic factor, but, some additional clinical factors may also have prognostic value. [ABSTRACT FROM AUTHOR]

In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis -benzimidazole derivatives (1–25) by using 3,3′-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (h CA-IX) was evaluated in-vitro , where several synthesized derivatives showed potent inhibition of h CA-IX (IC 50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 μM) and compounds 3–5 , 7–8 , 13–16 , 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC 50 = 18.24 ± 1.43 μM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents. [ABSTRACT FROM AUTHOR]

In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis -benzimidazole derivatives (1–25) by using 3,3′-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (h CA-IX) was evaluated in-vitro , where several synthesized derivatives showed potent inhibition of h CA-IX (IC 50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 μM) and compounds 3–5 , 7–8 , 13–16 , 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC 50 = 18.24 ± 1.43 μM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents. [ABSTRACT FROM AUTHOR]

Introduction: By definition, angiosarcoma is an epithelial cell tumor that forms in blood and lymphatic vessels. The pre-selection sites of angiosarcoma are the back of the head and neck, and the breast. Very rarely, angiosarcoma can be found in the liver and heart. Precisely because of its rarity, we wanted to show you the case of a patient with cardiac angiosarcoma at the age of 43. One can be found in the right atrium and ventricle, and the left atrium and ventricle, which are difficult to access for surgical treatment due to the position of the heart. This malignant tumor was located in the patient’s left atrium, which made the surgical treatment extremely physically demanding. Such tumor usually causes non-specific symptoms that often point to heart failure or arrhythmia. It very often metastasizes to the lymph nodes, liver, lungs and bones. Diagnostic tests that are performed for the purpose of diagnosing angiosarcoma of the heart are thoracic ultrasound of the heart, transesophageal ultrasound of the heart, computed tomography, coronary angiography, and positron emission tomography. After the diagnosis of angiosarcoma is made, the choices of treatment methods are chemotherapy, radiation and surgery depending on the size and localization. Case report: 43-years-old patient with irrelevant medical history has been transported from Varaždin General Hospital to University Hospital Centre “Sestre milosrdnice” because of arrhythmias. The patient stayed in the ward for 22 days in an isolation room due to vancomycin-resistant Enterococcus isolated in a rectal swab. During the hospitalization, a complete work-up was done to establish a diagnosis and start treatment. Also, during hospitalization, a complication occurred, the patient had an acute cerebral infarction due to tumor embolization. Mechanical thrombectomy was performed and the sample was sent for pathohistological analysis. The result of the pathohistological analysis is a malignant mesenchymal tumor - angiosarcoma. After the diagnosis, the patient is referred for cardiac surgery and presented for oncological treatment. The case we presented is specific because it is an angiosarcoma of the heart, which is a very rare heart tumor, so the experience of operating centers in the treatment of this malignant tumor is minimal. Angiosarcoma of heart is so rare that the world’s largest centers, such as cardiac surgery centers in the USA, had only 25 such patients in their database in 22 years. The survival of patients with primary angiosarcoma of the heart is significantly shorter than in those with angiosarcoma of another origin. The main cause of shorter survival is late diagnosis and the possibility that there are already distant metastases, most often in the lungs, brain, or bones. According to some studies, survival is longer in patients with sarcoma located in the left atrium, which does not have necrosis and, of course, without signs of metastatic disease. Such a rare malignant heart tumor presents a challenge for the entire multidisciplinary team. Conclusion: Nurses specific knowledge and skills are key in adequate care for the patient. Nursing assignments in the process of health care is educating the patient and their family. With education, psychological support and help must be provided. The process of health care must result in maximum preserving the quality of life, raising self-confidence and optimism with independence of the patient. To achieve that, nurse have to undertake a great deal of measures and interventions during health care. [ABSTRACT FROM AUTHOR]