[Expression and prognostic value of IL-6 and ß-catenin in oral squamous cell carcinoma].

PURPOSE: To investigate the expression of interleukin-6 (IL-6) and ß-catenin in oral squamous cell carcinoma (OSCC) and its clinicopathological significance. METHODS: The serum IL-6 concentration in 110 OSCC patients and 109 healthy controls were determined by chemiluminescence analysis. IL-6 and ß-catenin expression levels in 68 tumor specimens of OSCC patients undergoing surgical treatment and 6 normal mucosal tissues were determined by immunohistochemistry method. The correlation between IL-6 and ß-catenin and clinicopathological parameters and their prognostic value were analyzed. SPSS 22.0 software package was used for data analysis. RESULTS: Chemiluminescence method showed that the serum IL-6 content of OSCC patients was significantly increased (P＜0.001). Immunohistochemical results demonstrated that high expression of IL-6 in OSCC tissues was remarkably associated with cervical lymph node metastasis(P=0.017), pathological differentiation(P=0.014), recurrence and distant metastasis (P=0.048). OSCC patients with high IL-6 expression showed a poor prognosis by Kaplan-Meier survival analysis. Multivariate Cox regression analysis showed that high expression of IL-6 was an independent risk factor affecting the prognosis of patients with OSCC(P＜0.05). ß-catenin hyperexpression was associated with pathological differentiation(P=0.006) and overall poor survival in OSCC patients. Spearman correlation analysis showed a positive correlation between IL-6 and ß-catenin expression in OSCC (P＜0.001). CONCLUSIONS: Serum IL-6 is expected to be a biomarker for detection of OSCC, and IL-6 and ß-catenin expression in tumour tissues can be used as markers to evaluate the poor prognosis of OSCC.

A pooled analysis of adding olanzapine to guideline-recommended antiemetic therapy for breast cancer patients treated with an anthracycline and cyclophosphamide in prospective and retrospective studies.

PURPOSE: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. For better understanding the application of olanzapine in antiemetic strategies for breast cancer patients who suffered anthracycline plus cyclophosphamide-induced nausea and vomiting, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled-analyzed the results to confirm the efficacy and safety of olanzapine in breast cancer. METHODS: PubMed, Web of Science, EMBASE, and Cochrane CENTRAL databases were searched from inception through Sep 15, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate, and the secondary outcome was treatment-related adverse events. RESULTS: Four studies with 466 breast cancer patients were identified in the pooled analysis. In the acute period (0-24 h), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group, while in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. CONCLUSION: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.

Downstaging of Recurrent Advanced Hepatocellular Carcinoma After Lenvatinib Treatment: Opportunities or Pitfalls? A Case Report.

BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage that excludes them from potentially curative surgical treatment. Lenvatinib is associated with a high objective response rate (ORR) (40.6%) in advanced HCC, indicating the potential for tumor downstaging and conversion to surgical intervention. We report the case of a patient with recurrent, advanced HCC who achieved a partial response and downstaging following third-line treatment with lenvatinib but missed the opportunity for conversion hepatectomy. CASE PRESENTATION: A male Chinese patient aged 42 years presented with an obstructive liver lesion, revealed by CT imaging to be a single tumor in segments V and VIII of the liver, without macrovascular invasion. The patient had chronic hepatitis B infection, Barcelona Clinic Liver Cancer (BCLC) Stage A, normal liver function (Child-Pugh Score 5 and Grade A) and AFP level 4.45 ng/mL. The patient underwent a successful hepatectomy but experienced recurrence 14 months later. The recurrent tumor was detected at an early stage and the patient underwent successful radiofrequency ablation and transarterial chemoembolization. After a further 11 months, the patient experienced a second relapse characterized by multiple disseminated metastases in the left and right lobes of the liver and possible macrovascular invasion, equal to BCLC Stage B/C. The patient received lenvatinib and achieved a partial response with complete disappearance of a number of lesions, recovering to BCLC Stage A and becoming eligible for liver transplantation. However, the patient refused surgery and after 4 months experienced progressive disease. CONCLUSION: Our case suggests that radical treatment, such as conversion hepatectomy or liver transplantation, should be undertaken quickly following downstaging and within the expected PFS time associated with lenvatinib. However, further studies are required to provide additional evidence for this treatment strategy.

Exportin-5 SUMOylation promotes hepatocellular carcinoma progression.

Increasing evidence has shown that abnormal expression of XPO5 is found in many human cancers and acts as an oncoprotein in certain cancers. However, its functional role in hepatocellular carcinoma (HCC) remains unexplored. In our study, we found that XPO5 was highly expressed in HCC, which was associated with SUMO modification. Moreover, we found that XPO5 was SUMOylated by SUMO2 at K125. Functional experiments revealed that XPO5 SUMOylation could promote MHCC97H cell proliferation, migration and invasion. In addition, we found that the nuclear export of pre-miR-3184 was suppressed by SUMOylated XPO5. Moreover, PLCB1 was identified as the common target of miR-3184-5p and miR-3184-3p. The suppressed phenotype induced by miR-3184-5p and miR-3184-3p could be rescued by overexpression of PLCB1. Bioinformatics analysis showed that PLCB1 expression had a negative relationship with HCC patient survival. The inhibitory effects of MHCC97H cells resulted from abnormal XPO5 SUMO modification could be blocked by miR-3184 inhibitor or PLCB1 overexpression. In conclusion, our findings demonstrate a novel mechanism of XPO5 in HCC, that is, the SUMOylated XPO5 acts as an "oncogenic" role in MHCC97H cells proliferation, migration and invasion by controlling the nuclear-cytoplasm transportation of miR-3184, thus up-regulating PLCB1 expression.

Dynamic Changes in Serum Markers and Their Utility in the Early Diagnosis of All Stages of Hepatitis B-Associated Hepatocellular Carcinoma.

OBJECTIVE: This study aimed to evaluate the individual and combined diagnostic values of serum alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), glypican-3 (GPC3) and golgi protein 73 (GP73) in diagnosing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Participants from Beijing YouAn Hospital were enrolled and divided into seven groups. Serum was collected and the levels of AFP, GPC3, GP73 and DCP were simultaneously measured with a protein array. Pearson's χ2 test was applied to compare the clinicopathological characteristics. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance of the four markers. RESULTS: As a single biomarker for differentiating HCC from all controls, AFP had a larger area under the curve (AUC) (0.798, 95% CI (0.754-0.838) than the other biomarkers, with a sensitivity of 77.3% and a specificity of 71.1%. Among the other combinations, AFP plus GPC3 and DCP (0.871, 95% CI (0.833-0.903)) was the best at differentiating HCC from all controls. In discriminating very early stage and early stage HCC from all controls, the AUC of GPC3 (0.744, 95% CI (0.690-0.793); sensitivity 62.8%; specificity 83.3%) was better than that of AFP (0.723, 95% CI (0.668-0.774); sensitivity 67.3%; specificity 71.7%). Among all biomarker combinations, the combination of AFP, GPC3 and GP73 had the largest AUC (0.843, 95% CI (0.796-0.883); sensitivity 84.1%; specificity 71.7%). AFP (AUC 0.726, 95% CI (0.662-0.784)) showed the best performance in the very early diagnosis of HBV-related HCC. CONCLUSION: As a single biomarker, AFP has an advantage in the very early and early diagnosis of HBV-related HCC. The combination of AFP, GPC3 and GP73 is the most suitable marker for the early diagnosis of HBV-related HCC. However, AFP remains the best biomarker for the very early diagnosis of HBV-related HCC, and the adding of one or more markers does not significantly improve the diagnostic accuracy.

Analysis of potential key genes in very early hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the major pathological type of primary liver cancer, one of the leading causes of cancer death worldwide. In addition, the long-term survival rates of HCC still remain low. Therefore, we attempted to identify the potential key genes in the occurrence of HCC by comparing the expression profiles of very early HCC tissue samples with that of chronic cirrhotic tissue samples by integrating the bioinformatics analysis in this study. METHODS: Gene expression profiles of 19 very early HCC and 19 cirrhotic tissue samples were selected from GSE63898. Differentially expressed genes (DEGs) were also identified by using online tool GEO2R. Furthermore, the GO and KEGG enrichment analysis of the DGEs were conducted on DAVID datasets. Then a protein-protein interaction (PPI) network was constructed and the modules were analyzed based on STRING database and Cytoscape software. The hub genes were screened by applying the cytoHubba plugin and then analyzed with the Kaplan Meier plotter. RESULTS: A total of 118 DEGs were identified between very early HCC and cirrhotic tissue samples. These DGEs were strongly associated with several biological processes, such as negative regulation of growth and p53 signaling pathway. A PPI network was constructed and top eight hub genes, including CDKN3, CDK1, CCNB1, TOP2A, CCNA2, CCNB2, PRC1, and RRM2, were determined. High expressions of CDK1, CCNB1, TOP2A, CCNA2, PRC1, RRM2, CDKN3, and CCNB2 were associated with poorer overall survivals (OS) in HCC patients. CONCLUSION: We had compared the expression profiles between the very early HCC and cirrhotic tissue samples by using bioinformatics analysis tools, which might help us better to understand the molecular mechanism of the initiation of HCC and even to find novel targets for HCC therapy.

Treatment failure with propranolol for subglottic haemangioma.

The use of propranolol for the treatment of subglottic haemangioma has become hugely popular due to its effectiveness and safety profile. We report a case of 7-month-old boy who presented with stridor and histopathology suggestive of subglottic haemangioma following microlaryngoscopy and bronchoscopy (MLB). However, he did not respond to propranolol treatment. This could be due to an older age of propranolol commencement. In general, early commencement of propranolol is necessary when diagnosis of symptomatic infantile haemangioma is made to achieve maximal improvement in symptoms and prevent further proliferation. There should be a high index of suspicion for subglottic haemangioma in children presenting with chronic biphasic stridor, with early MLB and diagnosis. This will allow early treatment, giving the best chance to avoid our situation.

Associated measurement of fucosylated levels of AFP, DCP, and GPC3 for early diagnosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is a serious health problem worldwide, especially in Asian countries, such as China. However, there are difficulties in diagnosing and treating hepatocellular carcinoma. The alteration of fucosylated proteins was closely associated with carcinogenesis. This study is designed to evaluate the early diagnostic value of associated detection of fucosylated alpha-fetoprotein (fuc-AFP), fucosylated des-γ-carboxy prothrombin (fuc-DCP), and fucosylated glypican 3 (fuc-GPC3) in hepatocellular carcinoma. METHODS: All serum specimens collected from patients were diagnosed by complete clinicopathological examination and then subjected to the associated detection of fuc-AFP, fuc-DCP, and fuc-GPC3 by protein microarray. Canonical discriminant analysis was adopted to discriminate between the hepatocellular carcinoma group and the benign liver disease group. RESULTS: A total of 51 patients with hepatocellular carcinoma and 47 patients in the benign liver disease group were included in this study. Fuc-AFP, fuc-DCP, and fuc-GPC3 were significantly higher in the hepatocellular carcinoma group than in the benign liver disease group. The sensitivity, specificity, and accuracy of canonical discriminant analysis classification were 80.4%, 97.9%, and 88.8%, respectively. CONCLUSIONS: Fuc-AFP, fuc-DCP, and fuc-GPC3 are effective and useful tumor biomarkers. Associated measurement of these biomarkers with canonical discriminant analysis classification is a promising method for the early diagnosis of hepatocellular carcinoma.

Identification of key genes and pathways in hepatocellular carcinoma: A preliminary bioinformatics analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. However, the precise mechanisms of the development and progression of HCC remain unclear. The present study attempted to identify and functionally analyze the differentially expressed genes between HCC and cirrhotic tissues by using comprehensive bioinformatics analyses. METHODS: The GSE63898 gene expression profile was downloaded from the Gene Expression Omnibus (GEO) and analyzed using the online tool GEO2R to identify differentially expressed genes (DEGs). Gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs were performed in DAVID. The STRING database was used to evaluate the interactions of DEGs and to construct a protein-protein interaction (PPI) network using Cytoscape software. Hub genes were selected using the cytoHubba plugin and were validated with the cBioPortal database. RESULTS: A total of 301 DEGs were identified between HCC and cirrhotic tissues. The GO analysis results showed that these DEGs were significantly enriched in certain biological processes including negative regulation of growth and cell chemotaxis. Several significant pathways, including the p53 signaling pathway, were identified as being closely associated with these DEGs. The top 12 hub genes were screened and included TTK, NCAPG, TOP2A, CCNB1, CDK1, PRC1, RRM2, UBE2C, ZWINT, CDKN3, AURKA, and RACGAP1. The cBioPortal analysis found that alterations in hub genes could result in significantly reduced disease-free survival in HCC. CONCLUSION: The present study identified a series of key genes and pathways that may be involved in the tumorigenicity and progression of HCC, providing a new understanding of the underlying molecular mechanisms of carcinogenesis in HCC.

Primary mucosa-associated lymphoid tissue lymphoma of the hilar bile duct resulting in fluctuant jaundice: A case report.

RATIONALE: Primary mucosa-associated lymphoid tissue (MALT) lymphomas rarely originate in the hilar bile duct. Preoperative diagnosis of a primary MALT lymphoma of the hilar bile duct is difficult owing to the rarity of this disease. Differentiating between obstructive jaundice caused by MALT lymphoma of the hilar bile duct and hilar cholangiocarcinoma (the most common form of bile duct cancer) is challenging. PATIENT CONCERNS: A 57-year-old man presented to our hospital in August 2012 with fluctuant obstructive jaundice. DIAGNOSES: Contrast-enhanced abdominal computed tomography and magnetic resonance cholangiopancreatography showed a hilar liver mass measuring 23 × 28 mm along with intrahepatic biliary dilatation indicating hilar bile duct obstruction with a high index of suspicion for hilar cholangiocarcinoma. INTERVENTIONS AND OUTCOMES: Based on frozen section examination, he was intraoperatively diagnosed with chronic nonspecific inflammation. Histopathological and immunohistochemical examinations confirmed a diagnosis of malignant lymphoma, specifically classified as an extranodal marginal zone B-cell lymphoma of MALT type. LESSONS: A primary MALT lymphoma of the bile duct should be considered among the differential diagnosis in patients with a hilar tumor who present with fluctuating jaundice and are preoperatively diagnosed with suspected hilar cholangiocarcinoma, and/or an intraoperative diagnosis of chronic nonspecific inflammation (based on frozen section examination) assessed for stenosis or obstruction of the bile duct.

Analysis of serum alpha-fetoprotein (AFP) and AFP-L3 levels by protein microarray.

Objectives This study aimed to examine a simple, effective, time-saving, and low-cost protein microarray method for detecting serum alpha-fetoprotein (AFP) and AFP-L3 levels. Methods Serum samples from patients with hepatocellular carcinoma (HCC) (n = 33) and control subjects (n = 39) were collected and evaluated for the presence of AFP using a novel protein microarray. Glycoprotein (including AFP-L3) was enriched from crude samples by a Hotgen Biotech glycosyl capture spin column and then detected by protein microarray. An electrochemiluminescence immunoassay (ECLIA) was used to validate the measured values. Results Neither AFP levels lower than 20 ng/mL in the HCC group nor AFP levels higher than 20 ng/mL in the control group were found when tested by the ECLIA and protein microarray. The kappa test showed good consistency in the diagnostic performance of measuring serum AFP levels and the percentage of AFP-L3 in total AFP by the ECLIA and protein microarray. Protein microarray had advantages of smaller sample size required, low cost, and convenience compared with the ECLIA. Conclusion The protein microarray assay that was developed in the present study shows potential as an economic and convenient technique for detecting AFP and AFP-L3 levels in serum samples from patients with HCC.

Otitis Externa in Secondary Care: A Change in Our Practice Following a Full Cycle Audit

Abstract Introduction Patients presenting with otitis externa are a common thing in otolaryngology units. However, the practice has not been standardized due to a lack of consensus over the management of this condition in secondary care. The National Institute for Health and Care Excellence (NICE) guidelinehas beenpublished targetingthe general practitioners, but it may be relevant in cases of hospital first-time attenders. Objective To conduct an audit of the investigative and prescription practice for hospital first-time attenders in our department against the NICE guideline for otitis externa. Methods The case notes of the patients presenting with otitis externa were reviewed. The data collation included the performance of ear swabs and choice of eardrops. Results An initial audit showed that ear swabs were sent in 14 out of 19 cases, of which 11 grew either Pseudomonas aeruginosa or Staphylococcus aureus (organisms that are sensitive to empirical treatment). A re-audit showed higher adherence to NICE recommendations, with ear swabs sent in only 3 out of 25 cases. The initial audit also demonstrated Sofradex (Sanofi-Aventis, Paris, France) as the most popular empirical eardrop. Following our recommendation, the re-audit showed that Betnesol-N (GSK, Brentford, UK) was administered in 24 out of 25 cases. Conclusion We recommend Betnesol-N due to its cost-effectiveness. Ear swabs should be reserved for refractory cases only. Posters and email reminders are effective means of disseminating information within the hospital.

Spontaneous closure of branchial sinus of the pyriform fossa.

Management of third and fourth branchial cleft anomalies are similar. These anomalies should be suspected in a child with recurrent low-anterior neck abscess. Investigations in the form of cross-sectional studies and examination of the pharynx under anaesthesia will facilitate diagnosis and resolution of abscess. Spontaneous closure of the pyriform sinus can occur following conservative management with antibiotic treatment and abscess drainage. This emphasise the role of second-look prior to implementing endoscopic cauterisation or surgery.

NY-ESO-1 expression in hepatocellular carcinoma: A potential new marker for early recurrence after surgery.

NY-ESO-1 belongs to the cancer testis antigens (CTA) family, and is identified in a variety of tumors. Certain studies have demonstrated that NY-ESO-1 predicts tumor recurrence and treatment response. No reports are currently available regarding the correlation between NY-ESO-1 and the recurrence of hepatocellular carcinoma (HCC) following surgery. The purpose of the present study was to evaluate the association between NY-ESO-1 and relapse of HCC and to explore the possible mechanisms for this correlation. A total of 120 HCC patients were analyzed for the expression of NY-ESO-1 by immunohistochemistry (IHC). A stable NY-ESO-1 over-expressed HepG2 cell line (ESO-HepG2) was established to determine the biological effects of NY-ESO-1 on cell proliferation, cell cycle and migration by using the xCELLigence DP system, flow cytometry and xCELLigence SP system. NY-ESO-1 was positive in 28 of 120 (23.3%) HCC tumor tissues. NY-ESO-1 was not detectable in adjacent normal liver tissues. A close correlation was found between NY-ESO-1 expression and the recurrence of HCC following surgery (P=0.007). Kaplan-Meier analysis showed a shorter recurrence-free survival (RFS) for patients positive for NY-ESO-1 (log-rank test, P=0.003). The Cox regression model demonstrated that NY-ESO-1 expression was a significant independent predictor for the recurrence of HCC following curative surgery (P=0.022). Compared with HepG2 cells, ESO-HepG2 cells have increased migration but not proliferation ability. In conclusion, NY-ESO-1 expression is associated with worse HCC outcome following surgery, and the mechanism for this finding may be that NY-ESO-1 increases tumor cell migration.