Shorter Median Survival Time Research Articles

Establishment and Characterization of a Human Primary Myelofibrosis Cell Line

Aims: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal proliferation of stem cells and myeloid cells. JAK2, CARL, and MPL mutations could be detected in most patients, but 15% of PMF patients could be absent of these three gene mutations. PMF has shorter median survival time and poorer prognosis when compared with closely related MPNs, polycythemia vera (PV) and essential thrombocythemia (ET). Allogenic hematopoietic stem cells (allo-HSCT) is the only curative therapy for PMF patients, however transplantation-related complications and deaths were observed in more than 50% patients. Hydroxyurea and Ruxolitinib are commonly used drugs to improve clinical symptoms of PMF patients, but lack of anti-tumor activities. These drugs could not reverse bone marrow fibrosis or induce cytogenetic remission. Basic research work of PMF is limited as to the lack of human PMF cell line. Here, we aimed to establish and characterize a patient-derived human PMF cell line, which would provide a useful tool for PMF research and screenings for novel drugs.Methods: The bone marrow cells were obtained from a 61-year-old male patient, who was diagnosed as PMF for 2 years. Mono-nuclear cells were isolated and cultured in a continuous culture system. The cells were characterized by different methods, including STR profiling, morphology observation with Giemsa staining, flow cytometry, chromosome analysis, Epstein-Barr virus (EBV) detection, mycoplasma detection, whole-genome-exon sequencing, and cell proliferation assay.Results: The cells have continued to grow in liquid culture for more than 50 passages using the same culture conditions. Doubling time was about 48-72 hours. The STR profiling identified that the cultured cells and the patient's bone marrow cells were from the same origin. The cells are free from EBV and mycoplasma. Giemsa-Wrights staining showed primitive erythrocytes (Figure A), which was consistent with CD71 positive detected by flow cytometry. Chromosome analysis revealed a hyperdiploid karyotype, which was 47, XY,+12[1]/48,idem,+9[9]. Whole-genome-exon sequencing identified mutations of ASXL1, TP53, IKZF1, IDH1, FLT3, and TET1 (Figure B). Now this cell line, designated ZYXY-M2, is collected by China center for type culture collection (CCTCC).Discussion: Established cell lines are invaluable tools in cell biology. Right now, HEL and SET-2 are two cell lines that are most widely used in MPN-related researches. HEL is an erythroleukemia cell line which was derived from a patient with leukemia transformation of Hodgkin's disease, and SET-2 is a megakaryoblastic cell line which was derived from a patient with leukemic transformation of ET. Here, we established a cell line, ZYXY-M2, derived from a PMF patient and it would prove to be a valuable model for the study of PMF. ZYXY-M2 could help to explore the pathogenesis and development of PMF, novel drug screening, and may also help to set up xenograft PMF mouse models. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparative Review of Malignant Melanoma and Histologically Well-Differentiated Melanocytic Neoplasm in the Oral Cavity of Dogs.

Oral malignant melanoma (OMM) is the most common neoplasm of the canine oral cavity. It is characterized by its aggressive local disease as well as its high rate of lymphatic invasion and distant metastasis. OMM carries a poor prognosis, with most patients succumbing to the disease due to progression of the neoplasm. Histopathologically, OMM is characterized by significant nuclear atypia, a mitotic index of greater than 4/10 hpf, and evidence of vascular invasion or metastasis. Clinically, these lesions can become locally invasive, causing lysis of bones and severe inflammation of the surrounding soft tissue. With time, these lesions can spread to the regional lymph node and to the lungs and other organs. Prognosis can vary depending on the size of the primary tumor, regional node involvement, and distant metastatic disease; however, multiple studies report a relatively short median survival time ranging from less than 4 months to 8 months. Histologically well- differentiated melanocytic neoplasms (HWDMN) are a variant of OMM and sometimes referred to as canine oral melanocytic neoplasms of low malignant potential. Unlike OMM, patients with HWDMN have longer survival times. Histopathologically, HWDMNs have well-differentiated melanocytes with a low mitotic index of 3 or less per 10 hpf and minimal nuclear atypia. HWDMNs have better prognosis with a mean survival time of up to 34 months. This article is a comparative review of OMM and its less aggressive counterpart.

Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma.

Simple SummaryPancreatic cancer is a disease which is known to be highly deadly, with only 8% of people diagnosed surviving for more than 5 years. Multiple factors contribute to this poor survival rate, including a lack of early symptoms leading to late diagnosis and a high tendency for the cancer to rapidly spread throughout the body. Although there has been a lot of work in this area, we still lack an effective cure for pancreatic cancer. In this review, we aim to outline the latest research on possible treatments, including those which disrupt signalling pathways in the cell, disturb the cancers’ fuel sources, overload cancer cells with mutations, and re-direct the body’s immune system to attack the tumour. We also look at how we could eliminate a particularly aggressive group of cells within the tumour (‘cancer stem cells’) which are thought to be important to pancreatic cancer growth and spread.Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer that is strongly associated with poor prognosis and short median survival times. In stark contrast to the progress seen in other cancer types in recent decades, discoveries of new treatments in PDAC have been few and far between and there has been little improvement in overall survival (OS). The difficulty in treating this disease is multifactorial, contributed to by late presentation, difficult access to primary tumour sites, an ‘immunologically cold’ phenotype, and a strong tendency of recurrence likely driven by cancer stem cell (CSC) populations. Furthermore, apparently contrasting roles of tumour components (such as fibrotic stroma) and intracellular pathways (such as autophagy and TGFβ) have made it difficult to distinguish beneficial from detrimental drug targets. Despite this, progress has been made in the field, including the determination of mFOLFIRINOX as the standard-of-care adjuvant therapy and the discovery of KRASG12C mutant inhibitors. Moreover, new research, as outlined in this review, has highlighted promising new approaches including the targeting of the tumour microenvironment, enhancement of immunotherapies, epigenetic modulation, and destruction of CSCs.

Correlation between aspiration and long-term survival of inpatients with chronic obstructive pulmonary disease

Objective: To retrospectively analyze the high risk factors of death in patients with chronic obstructive pulmonary disease (COPD) and to explore the influence of aspiration on the long-term survival rate of COPD patients. Methods: A retrospective analysis of clinical data of inpatients, who were admitted to the First Affiliated Hospital of Guangzhou Medical University from April 2012 to December 2013 due to COPD exacerbations and had radionuclide aspiration test, was conducted. Meanwhile, we phoned the patients' family members, whose phone numbers were recorded in the electronic patient record system, to follow up the patients' survival status, and learn the causes of death from their death records if patients died during follow-up period. Inquired the resident administration patients belonging to according to their original address to get patient's current contact information if changed. Besides, if family members of patients failed to provide death record, we should look up information concerned from the medical records room of the hospital where they died. Results: The follow-up for the last patient was performed on February 20, 2017.The time span of this study is 58 months, starting from the radionuclide aspiration test for the first patient and ending with the follow-up for the last patient. 16 of the 53 patients(16/53, 30.2%)were tested positive whose average age was slightly higher than patients without aspiration (76.0±6.8 vs 70.9±9.9), but there was no significant difference between them(P=0.064). The aspiration rates among patients over and under the age of seventy were 14/35 and 2/18 respectively, and there was a significant difference between them(P = 0.03). Compared to the aspiration-negative patients, the aspiration-positive patients had higher incidence rate of pneumonia in COPD exacerbations (11/16 vs 9/37, χ²= 9.383, P = 0.002).The major cause of death in the patients with and without aspiration were respectively severe pneumonia and pulmonary encephalopathy(P<0.05 in both cases).Among COPD patients who took radionuclide aspiration test, the median survival time of the patients with and without aspiration were about 3 and 5 years respectively. The high-risk factors influencing long-term survival of the COPD patients with aspiration included ICU-involved medical history and accompanying pneumonia. Conclusions: The incidence rate of aspiration is relatively high in COPD patients over 70 years old. Compared to COPD patients without aspiration, COPD patients with aspiration have higher incidence rate of pneumonia and shorter median survival time. ICU-involved medical history and severe pneumonia are the two high-risk factors influencing long-term survival of COPD patients with aspiration.To improve the survival time of COPD patients with aspiration, we need to attach importance to the prevention and treatment of aspiration.

PSMA-Targeting Radiopharmaceuticals for Prostate Cancer Therapy: Recent Developments and Future Perspectives.

Simple SummaryOne of the most frequently diagnosed cancer in men is adenocarcinoma of the prostate. Once the disease is metastatic, only very limited treatment options are available, resulting in a very short median survival time of 13 months; however, this reality is gradually changing due to the discovery of prostate-specific membrane antigen (PSMA), a protein that is present in cancerous prostate tissue. Researchers have developed pharmaceuticals specific for PSMA, ranging from antibodies (mAb) to low-molecular weight molecules coupled to beta minus and alpha-emitting radionuclides for their use in targeted radionuclide therapy (TRT). TRT offers the possibility of selectively removing cancer tissue via the emission of radiation or radioactive particles within the tumour. In this article, the major milestones in PSMA ligand research and the therapeutic developments are summarised, together with a future perspective on the enhancement of current therapeutic approaches.Prostate cancer (PC) is the second most common cancer among men, with 1.3 million yearly cases worldwide. Among those cancer-afflicted men, 30% will develop metastases and some will progress into metastatic castration-resistant prostate cancer (mCRPC), which is associated with a poor prognosis and median survival time that ranges from nine to 13 months. Nevertheless, the discovery of prostate specific membrane antigen (PSMA), a marker overexpressed in the majority of prostatic cancerous tissue, revolutionised PC care. Ever since, PSMA-targeted radionuclide therapy has gained remarkable international visibility in translational oncology. Furthermore, on first clinical application, it has shown significant influence on therapeutic management and patient care in metastatic and hormone-refractory prostate cancer, a disease that previously had remained immedicable. In this article, we provide a general overview of the main milestones in the development of ligands for PSMA-targeted radionuclide therapy, ranging from the firstly developed monoclonal antibodies to the current state-of-the-art low molecular weight entities conjugated with various radionuclides, as well as potential future efforts related to PSMA-targeted radionuclide therapy.

Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer

Objective To investigate the expression of Cripto-1 in pancreatic cancer and to analyze its clinical significance. Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ 2=4.787,P=0.029).However,multivariate analysis failed to demonstrate overexpression of Cripto-1 an independent prognostic indicator in patients with pancreatic cancer(HR=1.341,95% CI=0.800-2.248,P=0.266).Conclusions Cripto-1 may play an important role in the development and progression of pancreatic cancer.It can be a potential prognostic biomarker for patients with pancreatic cancer.

Different muscle mass indices of the Global Leadership Initiative on Malnutrition in diagnosing malnutrition and predicting survival of patients with gastric cancer

ObjectiveMalnutrition is common and related to negative prognosis in patients with gastric cancer (GC). The Global Leadership Initiative on Malnutrition (GLIM), a novel consensus for the diagnosis of malnutrition, was proposed recently. However, the roles of GLIM in diagnosing malnutrition and predicting overall survival (OS) in patients with GC have been unclear. MethodWe conducted a multicenter, observational cohort study including 877 hospitalized patients with GC 2013 through 2018. Different anthropometric measurements were compared to assess reduced muscle mass. Kaplan-Meier curves and multivariate Cox regression were used to analyze the relationship between GLIM-defined malnutrition and the OS of patients with GC. Independent prognostic variables were incorporated to develop a nomogram for individualized survival prediction. The calibration curve was used to determine the predictive accuracy and discriminatory capacity of the nomogram. In addition, 219 patients with GC were enrolled for external validation. ResultsA total of 464 (53%) patients with GC were diagnosed with malnutrition. Patients diagnosed with severe malnutrition based on either midarm circumference or body weight–standardized hand grip strength had a shorter median survival time (16.7 mo; interquartile range, 8.4–32.7 mo) and a higher hazard ratio (HR, 1.49; 95% CI, 1.15–1.92; P = 0.002). Severe malnutrition was an independent risk factor for OS (HR, 1.32; 95% CI, 1.02–1.71; P = 0.038). The GLIM nomogram showed good performance in predicting 3-y survival in patients with GC. ConclusionsOur findings support the effectiveness of GLIM in diagnosing malnutrition and predicting OS in patients with GC.

Imaging features and outcomes in patients with ruptured hepatocellular carcinoma following transcatheter arterial chemoembolization: a retrospective clinical study.

ObjectiveTo summarize and analyze the imaging features and outcomes of patients with ruptured hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE).MethodsWe investigated all consecutive patients with HCC who received standardized TACE based on our hospital database. Ruptured HCCs were divided into three types according to their relationship with the liver capsule, determined by computed tomography or magnetic resonance imaging scans: Type I, portion of tumor cambered outwards ≤30%; Type II, portion of tumor cambered outwards >30% and <50%; and Type III, portion of tumor cambered outwards ≥50%.ResultsThere were 54, 40, and 26 patients with Type I, II, and III HCCs, respectively. Among these, eight patients developed ruptured tumors within 2 weeks after TACE, including one, two, and five patients with type I, II, and III ruptured HCCs, respectively. Patients with type III HCCs had a shorter median survival time than patients with type I–II HCCs.ConclusionsPatients with type III HCCs might have a higher re-rupture rate and benefit less from emergency arterial embolization procedures than patients with type I–II HCCs.

Hematologic and clinical characteristics of dogs with circulating macrophage-like cells.

Macrophage-like (ML) cells are rarely observed on blood smear examinations, and the significance of these cells has been poorly described. The objective of this study was to retrospectively describe selected hematologic and clinical characteristics of dogs with ML cells in peripheral blood. Complete blood count (CBC) reports with blood smear evaluations from the clinical pathology laboratory records at North Carolina University College of Veterinary Medicine were retrospectively reviewed. Data were collected over a 10-year-period. Dogs were defined as having circulating ML cells if three or more ML cells were present on a single blood smear. Hematologic and clinical data of dogs with circulating ML cells were compared with age-matched hospital-derived control dogs. Of 61,631 CBC records, 87 reports (0.14%) described the presence of ML cells. Thirty-nine dogs met the inclusion criteria. The hemogram of dogs with circulating ML cells was characterized by a pronounced inflammatory and stress leukogram, anemia, and thrombocytopenia. Of the 39 dogs, 19 (49%) had systemic or severe localized inflammatory/necrotic diseases. Eighteen (46%) dogs were diagnosed with neoplasia of histiocytic (5) and non-histiocytic origins (13). Dogs with circulating ML cells had a shorter median survival time (34days) than the control dogs (595days, P<.0001), with an increased occurrence of death/euthanasia within 1month (3.89-fold). However, the presence of circulating ML cells was not found to be an independent prognostic factor in a multivariable model. The hemograms and diagnoses of dogs with ML cells suggest that severe inflammatory conditions or histiocytic and non-histiocytic neoplasia are common causes for circulating ML cells.

Clinical features and outcome of dogs and cats with bidirectional and continuous right-to-left shunting patent ductus arteriosus.

BackgroundStudies describing the clinical progression of animals with reverse patent ductus arteriosus (PDA) are lacking.ObjectivesTo describe the signalment, presenting signs, echocardiographic features, and survival in a group of dogs and cats with bidirectional and continuous right‐to‐left PDA.AnimalsForty‐six client‐owned animals included, comprising 43 dogs and 3 cats with bidirectional or continuous right‐to‐left PDA.MethodsRetrospective multicenter study. Medical records and echocardiographic findings reviewed from animals diagnosed with bidirectional or continuous right‐to‐left PDA. Impact of ductal morphology, spectral Doppler flow profile, PCV, sildenafil treatment at presentation, sildenafil dose, severity of pulmonary hypertension, general anesthesia with or without surgery and the presence of right‐sided congestive heart failure (R‐CHF) on crude mortality rate were evaluated via Mantel‐Cox log rank comparison of Kaplan‐Meier survival curves. Univariable and multivariable Cox proportional hazards analysis was performed, and hazard ratio (HR) (95% confidence intervals [CI]) was presented.ResultsHindlimb collapse was the most common presenting sign in dogs (n = 16). Clinical signs in cats were variable. Median survival time was 626 days in dogs (range 1‐3628 days). Dogs with R‐CHF had a shorter median survival time (58 days vs 1839 days, P = .03). Dogs treated with sildenafil at initial presentation survived longer (1839 days vs 302 days, P = .03), which was the only independent predictor of survival (HR 0.35, CI 0.15‐0.86, P = 0.021).Conclusions and Clinical ImportanceDogs and cats with reverse PDA have a variable clinical presentation and prognosis. Survival time was longer in animals prescribed sildenafil at diagnosis. Dogs with R‐CHF at presentation have a worse overall outcome.

Mechanisms and functions of long non‑coding RNAs in glioma (Review).

Glioma is one of the most common primary malignancies of the adult central nervous system with malignancy grades betweenI‑IV. Among these four grades, glioblastoma is the most malignant and aggressive type of tumor and is characterized by a poor prognosis, high recurrence rate and short median survival time after initial diagnosis. Existing treatments, such as radiotherapy, chemotherapy and surgical resection, have poor therapeutic effects; therefore, it is necessary to discover novel targeted therapies to enhance the curative effect and improve prognosis. Recently, increasing evidence has shown that long non‑coding RNAs (lncRNAs) participate in the vast majority of key physiological and pathological processes. Moreover, aberrant expression levels of lncRNAs are closely associated with the occurrence and development of glioma and other malignant phenotypes. The present review summarizes new insights into the functions and mechanisms of lncRNAs at the epigenetic, transcriptional and post‑transcriptional levels, describes their ability to encode functional peptides in glioma and discusses their clinical potential as new biomarkers and prospective therapeutic targets.

Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer and the majority of patients are diagnosed at an advanced stage and have a poor prognosis. AKR1C3 (Aldo-keto reductase family 1 member C3) and AKR1D1 (Aldo-keto reductase family 1 member D1) catalyze the conversion of aldehydes and ketones to alcohols and play crucial roles in multiple cancers. However, the functions of AKR1C3 and AKR1D1 in HCC remain unclear. In our study, data from the public databases were selected as training and validation sets, then 76 HCC patients in our center were chosen as a test set. Bioinformatics methods suggested AKR1C3 was overexpressed in HCC and AKR1D1 was down-regulated. The receiver operating characteristic curve (ROC) analysis was performed and the area under curve (AUC) values of AKR1C3 and AKR1D1 were above 0.7 (0.948, 0.836, respectively). Also, the high expression of AKR1C3 and low expression of AKR1D1 predicted poor prognosis and short median survival time. Then, the knockdown of AKR1C3 and overexpression of AKR1D1 in HCC cells were achieved with lentivirus. And both decreased cell proliferation, restrained cell viability, and inhibited tumorigenesis. Moreover, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted and the results showed that AKR1C3 and AKR1D1 might participate in the MAPK/ERK and androgen receptor (AR) signaling pathway. Furthermore, the AR and phosphorylated ERK1/2 were significantly reduced after the suppression of AKR1C3 or overexpression of AKR1D1. Collectively, AKR1C3 and AKR1D1 might serve as candidate diagnostic and prognostic biomarkers for HCC and provide potential targets for HCC treatment.

The deleterious effects of smoking resumption after heart transplantation

Aims Smoking is linked to disease and survival in the general and transplant population. We studied the smoking history, disease and survival of patients after heart transplantation. Methods A total of 130 patients who underwent heart transplantation between 1995 and 2019 received a questionnaire to document their smoking history. We assessed patient characteristics, comorbidities and survival. Results Sixty-five per cent of patients were active or former smokers prior to heart transplantation. All patients stopped smoking; 26% of the former smokers resumed smoking after transplantation. Patients who resumed smoking were younger at the time of transplantation, used fewer statins and were more likely to be treated with azathioprine after transplantation. The mean follow-up for all patients was 11 ± 5.5 years. Patients who resumed smoking were more likely to develop solid organ cancers (45%) compared to those who remained abstinent (23%) and those who never smoked (13%) (p 0.014). A Cox proportional hazards regression analysis identified smoking resumption, with a RR of 2.31 (1.14–4.68, p 0.02), and age at transplantation, with a RR of 1.03 (1–1.06, p 0.034), as significant for survival. Patients resuming smoking after transplantation had a significantly higher risk of dying from solid organ cancer, with a RR of 2.54 (1.03, 6.28; p 0.04) with a short median survival time (25th–75th percentile) of (1 (0–5) months, p 0.007). Conclusion Patients who resume smoking after heart transplantation have worse survival and are at higher risk of dying from solid organ cancer. Implementing a smoking cessation plan throughout the post-transplant period is important.

Identification of a 6-Gene Signature Associated with Resistance to Tyrosine Kinase Inhibitors: Prognosis for Clear Cell Renal Cell Carcinoma.

BackgroundTyrosine kinase inhibitors (TKIs) are used to treat metastatic disease associated with clear cell renal cell carcinoma (ccRCC); however, most patients develop resistance after 6 to 15 months. As such, identifying biomarkers of TKI resistance may be useful for prognosis.Material/MethodsWe analyzed ChIP-seq data related to TKI resistance from the Gene Expression Omnibus and RNA-Seq and clinical data from The Cancer Genome Atlas database. We used univariate Cox analysis and Cox regression/Lasso analysis to determine a risk score. The Kaplan-Meier estimate and receiver operating characteristic curve verified the risk score’s sensitivity and specificity. The stratified analysis and the univariate and multivariate analyses revealed its predictive power. We predicted survival time by constructing a nomogram.ResultsOf the 32 differentially expressed genes (DEGs) related to TKI resistance, 6 (ACE2, MMP24, SLC44A4, C1R, C1ORF194, ADAMTS15) were used to establish a risk score. Kaplan-Meier analysis showed that high-risk patients had shorter median survival times than low-risk patients, notably among those with metastatic disease (1.51 vs. 4.55 years). The stratified analysis revealed that patients with advanced disease had relatively higher risk scores than patients at early stages (P<0.001). Univariate analysis independently associated the 6-DEGs signature with the prognosis of metastatic ccRCC (hazard ratio, 1.217; 95% confidence interval, 1.090–1.358). The nomogram we constructed based on 6-DEGs signature and clinical parameters predicted survival time accurately.ConclusionsWe identified a 6-DEGs signature that permitted us to establish a risk score related to TKI resistance that can serve as a reliable biomarker for predicting the survival of patients with ccRCC.

Expression of Phosphorylated Signal Transducer and Activator of Transcription 3 and its Prognostic Significance in Canine Anal Sac Adenocarcinoma

Prognostication in canine anal sac adenocarcinomas (ASACs) is difficult due to conflicting evidence regarding metastatic rates and median survival times (MSTs). The transcription factor signal transducer and activator of transcription 3 (STAT3) is a prognostic predictor in several human cancers. The aim of this retrospective study was to assess STAT3 expression in ASACs and to explore its association with clinical presentation and outcome. We hypothesized that STAT3 expression would distinguish tumours with early versus late metastasis. Records from The Queen's Veterinary School Hospital, Cambridge, UK, were searched for dogs diagnosed with ASAC from 2008 to 2019. Immunohistochemical expression of phosphorylated STAT3 (pSTAT3) was assessed in primary tumours (n=57) and metastatic lymph nodes (n=30) and MSTs were calculated for cases with low and high pSTAT3 expression. Of the 57 cases assessed, 27 presented with primary tumours but no metastasis and 30 with both primary and local metastatic disease. Most cases (50/57) expressed nuclear pSTAT3 within neoplastic cells in both primary tumour and metastatic lymph nodes. pSTAT3 expression was predominantly observed in neoplastic cells at the edges of neoplastic lobules, suggesting a potential role in invasion. There was no significant difference in pSTAT3 expression between cases metastatic at presentation and those that did not have detectable metastasis at presentation. There was no significant difference between the MSTs in cases with high and low pSTAT3 expression. Cases that presented with metastatic disease had shorter MSTs (395 days) than those with primary tumours alone (623 days). Although pSTAT3 is variably expressed in primary and metastatic ASAC cells, pSTAT3 did not provide prognostic information for canine ASAC.

Evaluation of epithelial and mesenchymal cell markers in canine urinary bladder transitional cell carcinoma

Canine transitional cell carcinoma (cTCC) is the most common malignant tumour in the urinary bladder: it is highly invasive and exhibits metastatic characteristics. Inflammation is also strongly related to cTCC. Epithelial tumours often exhibit a mesenchymal cell phenotype during tumour invasion and metastasis owing to epithelial-mesenchymal transition (EMT), which is often induced in chronic inflammation. The aim of this retrospective study was to investigate the expression of epithelial and mesenchymal cell markers in tumour cells and to evaluate its relationship with prognosis of cTCC. In this study, 29 dogs with cTCC who underwent surgical treatment were enrolled. Clinical parameters were reviewed using medical records. Tissue expression of epithelial and mesenchymal markers was evaluated by immunohistochemical analysis. The association between the expression of mesenchymal cell markers and clinical parameters, including prognosis, was statistically examined.In five normal bladder tissues used as controls, no expression of mesenchymal markers was observed, except for one tissue that expressed fibronectin. Conversely, epithelial tumour cells expressed vimentin and fibronectin in 23/29 and 19/28 cTCC tissues, respectively. Regarding clinical parameters, vimentin score in Miniature Dachshunds was significantly higher than those in other dog breeds (P < 0.001). Multivariate survival analyses revealed that age>12 years was related to shorter progression-free survival (P = 0.02). Higher vimentin score, lower fibronectin score, and advanced clinical T stage were significantly correlated with shorter median survival time (P < 0.05). The results of this study indicate that vimentin expression was associated with cTCC progression. Further studies are needed to examine the incidence and relevance of EMT in cTCC.

Clinicopathological characteristics and treatment outcomes of cutaneous extranodal natural killer/T-cell lymphoma: a retrospective study in China.

BackgroundExtranodal natural killer/T-cell lymphoma (ENKTL) is a special subtype of non-Hodgkin lymphoma that is subcategorized into ENKTL-nasal and ENKTL-nasal type. Cases with extranasal involvement show an aggressive clinical course with poor prognosis and low survival rates. The skin is the second most commonly affected organ, and such cases are defined as cutaneous ENKTL. However, there is limited information on the clinicopathologic features and prognostic factors of cutaneous ENKTL.MethodsWe reviewed the pathologic, immunohistochemical, and clinical data for 47 cases of cutaneous ENKTL.ResultsCutaneous ENKTL mainly involved the torso and extremities, with lesions presenting as single or multiple nodules, erythema and rash, or painless necrotic ulcers. There was high surface CD3 expression. The median survival time was 4.0 months (95% CI: 2.3–5.7 months). Stage I/II patients had a better outcome, with a mean survival time of >26 months (95% CI: 17.68–35.92 months). Stage III/IV patients had very poor outcome, with overall survival of 4.7 months (95% CI: 1.01–2.73 months). The presence of B symptoms, advanced tumor stage, increased lactate dehydrogenase level, high International Prognostic Index (IPI), and abnormal hemoglobin were independent prognostic factors for poor survival. Patients were more responsive to treatment with an L-asparaginase-based chemotherapy regimen than to other therapeutic approaches.ConclusionsCutaneous and primary nasal ENKTL differ in terms of clinical and biological characteristics. Cutaneous ENKTL has a short median survival time. Although an L-asparaginase-containing chemotherapy regimen was effective, a standardized treatment strategy remains to be established for cutaneous ENKTL.

The predictive value of RDW in AKI and mortality in patients with traumatic brain injury.

BackgroundRed blood cell distribution width (RDW) has been validated valuable in predicting outcome and acute kidney injury (AKI) in several clinical settings. The aim of this study was to explore whether RDW is associated with outcome and AKI in patients with traumatic brain injury (TBI).MethodsPatients admitted to our hospital for TBI from January 2015 to August 2018 were included in this study. Multivariate logistic regression analysis was performed to identify risk factors of AKI and outcome in patients with TBI. The value of RDW in predicting AKI and outcome was evaluated by receiver operating characteristic (ROC) curve.ResultsThree hundred and eighteen patients were included in this study. The median of RDW was 14.25%. We divided subjects into two groups based on the median and compared difference of variables between two groups. The incidence of AKI and mortality was higher in high RDW (RDW > 14.25) group (31.45% vs 9.43%, P < .001; 69.81% vs 29.56%, P < .001). Spearman's method showed RDW was moderately associated with 90‐day Glasgow Outcome Scale (GOS) (P < .001). In multivariate logistic regression analysis, RDW, lymphocyte, chlorine, and serum creatinine were risk factors of AKI. And Glasgow Coma Scale (GCS), glucose, chlorine, AKI, and RDW were risk factors of mortality. The area under the ROC curve (AUC) of RDW for predicting AKI and mortality was 0.724 (0.662‐0.786) and 0.754 (0.701‐0.807), respectively. Patients with higher RDW were likely to have shorter median survival time (58 vs 70, P < .001).ConclusionsRed blood cell distribution width is an independent risk factor of AKI and mortality in patients with TBI.

Effect of perioperative desmopressin in cats with mammary carcinoma treated with bilateral mastectomy.

Perioperative administration of desmopressin has shown to significantly decrease rates of local recurrence and metastasis, and increase survival times in dogs with grade II and III mammary carcinomas. The objective of this study was to compare the oncologic outcome of cats with mammary carcinoma treated with bilateral mastectomy with or without perioperative administration of desmopressin. Medical records from nine veterinary institutions were searched to identify cats diagnosed with mammary carcinoma treated with bilateral mastectomy. Sixty cats treated with single-session or staged bilateral mastectomy were included. There were no significant differences in oncologic outcomes found between cats treated and not treated with desmopressin. No adverse effects were seen in any of the cats treated with perioperative desmopressin. Postoperative complications occurred in 18 cats (38.3%) treated with single-session bilateral mastectomy and in three cats (23.1%) treated with staged bilateral mastectomy (P=.48). Histologic grade and a modification of a proposed five-stage histologic staging system were both prognostic for disease-free interval. Incomplete histologic excision was associated with significantly increased rates of metastasis and tumour progression, and a shorter median survival time (MST). Cats that developed local recurrence also had a significantly shorter MST. The results of this study do not support the use of perioperative desmopressin to improve outcome when performing bilateral mastectomy for the treatment of mammary carcinoma in cats.

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC.

Lung cancer is the cause of a fourth of all cancer-related deaths. About a third of all lung adenocarcinoma tumours harbour mutations on exons 18 to 21 of the epidermal growth factor receptor (EGFR) gene. Detection of these mutations allows for targeted therapies in the form of EGFR Tyrosine kinase inhibitors. Recently, "liquid biopsies" have emerged as an alternative to conventional tissue mutation detection. In this pilot study, we attempted to optimize EGFR mutation detection from malignant pleural effusions (MPEs) as "liquid biopsies" when tissue biopsies were unavailable. Resulting mutations were then to be mapped on the EGFR gene and explored using cBioPortal, a public cancer genomic database. We first attempted a direct sequencing approach and showed that single nucleotide variants (SNVs) were likely to be missed in MPEs. We then switched to and optimized an EGFR mutant-specific quantitative polymerase chain reaction-based assay. This assay was piloted on n = 10 pleural effusion samples (one non-malignant pleural effusion as a negative control). 5/9 (55.55%) samples harboured EGFR mutations with 2/9 (22.22%) being exon 19 deletions and 3/9 (33.33%) the S768I mutation. The frequency of the S768I SNV in our study was significantly higher than that observed in other studies (~0.2%). Utilizing cBioPortal data, we report that patients with S768I have a shorter median survival time (6 months vs 38 months), progression-free survival time (8 months vs 44 months) and lower tumor mutation count compared to patients with other EGFR mutations. The shorter survival of patients with the S768I SNV predicts aggressive disease and poor prognosis as a result of this mutation. Studies in larger cohorts and/or animal models are necessary to confirm these findings.