Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin.

BACKGROUND: Serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a promising biomarker for hepatocellular carcinoma (HCC) surveillance. AIM: To identify the contributing factors related to the abnormal elevation of PIVKA-II level and assess their potential influence on the performance of PIVKA-II in detecting HCC. METHODS: This study retrospectively enrolled in 784 chronic liver disease (CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve (AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-II for HCC, respectively. RESULTS: Elevated PIVKA-II levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase (ALP), and total bilirubin (TBIL) for CLD patients and aspartate aminotransferase (AST) and tumor size for HCC patients (all P < 0.05). Serum PIVKA-II were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal (ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST (all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-II was significantly higher compared to that in patients with TBIL > 1 × ULN (0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant (0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone. CONCLUSION: Serum PIVKA-II has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Microbial spectrum and drug resistance of pathogens cultured from gallbladder bile specimens of patients with cholelithiasis: A single-center retrospective study.

BACKGROUND: Bacterial infection is an important cause of cholelithiasis or gallstones and interferes with its treatment. There is no consensus on bile microbial culture profiles in previous studies, and identified microbial spectrum and drug resistance is helpful for targeted preventive and therapeutic drugs in the perioperative period. AIM: To analyze the bile microbial spectrum of patients with cholelithiasis and the drug susceptibility patterns in order to establish an empirical antibiotic treatment for cholelithiasis-associated infection. METHODS: A retrospective single-center study was conducted on patients diagnosed with cholelithiasis between May 2013 and December 2018. RESULTS: This study included 185 patients, of whom 163 (88.1%) were diagnosed with gallstones and 22 (11.9%) were diagnosed with gallstones and common bile duct stones (CBDSs). Bile culture in 38 cases (20.5%) was positive. The presence of CBDSs (OR = 5.4, 95%CI: 1.3-21.9, P = 0.03) and longer operation time (> 80 min) (OR = 4.3, 95%CI: 1.4-13.1, P = 0.01) were identified as independent risk factors for positive bile culture. Gram-negative bacteria were detected in 28 positive bile specimens, and Escherichia coli (E. coli) (19/28) and Klebsiella pneumoniae (5/28) were the most frequently identified species. Gram-positive bacteria were present in 10 specimens. The resistance rate to cephalosporin in E. coli was above 42% and varied across generations. All the isolated E. coli strains were sensitive to carbapenems, with the exception of one imipenem-resistant strain. K. pneumoniae showed a similar resistance spectrum to E. coli. Enterococcus spp. was largely sensitive to glycopeptides and penicillin, except for a few strains of E. faecium. CONCLUSION: The presence of common bile duct stones and longer operation time were identified as independent risk factors for positive bile culture in patients with cholelithiasis. The most commonly detected bacterium was E. coli. The combination of ß-lactam antibiotics and ß-lactamase inhibitors prescribed perioperatively appears to be effective against bile pathogens and is recommended. Additionally, regular monitoring of emerging resistance patterns is required in the future.

An 11-gene signature for the prediction of systemic recurrences in colon adenocarcinoma.

BACKGROUND: Prognosis varies among patients within the same colon adenocarcinoma (COAD) stage, indicating the need for reliable molecular markers to enable individualized treatment. This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD. METHODS: Gene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database (n = 332) and The Cancer Genome Atlas database (n = 431). The relationship between gene signature and relapse-free survival was analysed in the training set (n = 93) and validated in the internal validation set (n = 94) and external validation sets (n = 145 and 431). RESULTS: Overall, 11 genes (N-myc downstream regulated gene 1 [NDRG1], fms-like tyrosine kinase 1 [FLT1], lipopolysaccharide binding protein [LBP], fatty acid binding protein 4 [FABP4], adiponectin gene [ADIPOQ], angiotensinogen gene [AGT], activin A receptor, type II-like kinase 1 [ACVRL1], CC chemokine ligand 11 [CCL11], cell division cycle 42 [CDC42], T-cell receptor alpha variable 9_2 [TRAV9_2], and proopiomelanocortin [POMC]) were identified by univariable and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Based on the risk-score model, the patients were grouped into the high-risk or low-risk groups using the median risk score as the cut-off. The area under the curve (AUC) values for 1-, 3-, and 5-year recurrence were 0.970, 0.849, and 0.859, respectively. Patients in the high-risk group had significantly poorer relapse-free survival than did those in the low-risk group. The predictive accuracy of the 11-gene signature was proven in the validation sets. Our gene signature showed better predictive performance for 1-, 3-, and 5-year recurrence than did the other four models. CONCLUSIONS: The 11-gene signature showed good performance in predicting recurrence in COAD. The accuracy of the signature for prognostic classification requires further confirmation.

Autophagy inhibitors increase the susceptibility of KRAS-mutant human colorectal cancer cells to a combined treatment of 2-deoxy-D-glucose and lovastatin.

RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 µM) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G2/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 µM) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.

Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice.

BACKGROUND: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. METHODS: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. RESULTS: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1ß) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. CONCLUSION: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

Factors contributing to diagnostic delay of Caroli syndrome: a single-center, retrospective study.

BACKGROUND: Caroli syndrome (CS) is a rare congenital disorder without pathognomonic clinical symptoms or laboratory findings; therefore, the diagnosis is often delayed. The objective of this study was to investigate the diagnostic delay and associated risk factors in CS patients. METHODS: This was a retrospective analysis of 16 CS patients admitted to a single tertiary medical center on mainland China. The diagnostic timelines of CS patients were reviewed to demonstrate the initial findings of CS at diagnosis, the risk factors associated with diagnostic delay, and potential clues leading to early diagnosis. RESULTS: The median diagnostic delay was 1.75 years (range: 1 month to 29 years, interquartile range: 6.2 years) in 16 enrolled CS patients. Sex, age, and initial symptoms were not associated with diagnostic delay. 87.5% of CS patients were diagnosed by imaging, and the accuracies of ultrasonography, computed tomography (CT), and magnetic resonance cholangiopancreatography were 25, 69.2, and 83.3%, respectively. The median diagnostic delays for patients with or without CT performed at the first hospital visited according to physician and radiologist suspicion of the diagnosis were 7.4 months and 6 years, respectively (p = 0.021). Hepatic cysts with splenomegaly were detected by ultrasound in over half of CS patients. CONCLUSIONS: The majority of CS patients were not diagnosed until complications of portal hypertension had already developed. Recognition and early suspicion of the disease were important factors influencing diagnostic delay of CS. Hepatic cysts plus splenomegaly detected by US might raise the clinical suspicion to include CS in the differential diagnosis.

Antitumor immunity of low-dose cyclophosphamide: changes in T cells and cytokines TGF-beta and IL-10 in mice with colon-cancer liver metastasis.

BACKGROUND: The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer. Low-dose cyclophosphamide (CTX) is widely believed to be involved in the modulation of the immune system. However, the underlying mechanism of low-dose CTX remains unknown. This study aimed to investigate the antitumor immunity of low-dose CTX in the treatment of colon-cancer liver metastasis. METHODS: Thirty mice were randomly divided into five groups. After liver metastasis was established in colon-cancer models, mice in the treatment groups were injected with low-dose CTX (20 mg/kg) at different time points. Liver and spleen tissues were examined for T-cell markers via flow cytometry. Interleukin (IL)-10 and transforming growth factor (TGF)-ß1 expression levels in liver tissues were analysed by immunohistochemistry. Serum interferon (IFN)-γ and IL-10 levels were detected by enzyme-linked immunosorbent assay. An additional 20 mice were randomly allocated into two groups and the survival times were recorded. RESULTS: The expression levels of CD4+ T cells, CD8+ T cells, and IFN-γ were down-regulated, whereas those of IL-10 and TGF-ß1 were up-regulated in liver metastasis from colon cancer in mice. Furthermore, the local and systemic microenvironments of the liver were altered, which led to reduced antitumor immune responses and subsequently liver metastasis. However, treatment with low-dose CTX reversed these effects. The survival times of mice treated with low-dose CTX were significantly longer than those of the other groups. CONCLUSIONS: Low-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation in mice. CTX could be used as a drug to prevent and treat liver metastasis from colon cancer.

Tumor Cell-Secreted ISG15 Promotes Tumor Cell Migration and Immune Suppression by Inducing the Macrophage M2-Like Phenotype.

Interferon-stimulated gene 15 (ISG15) is known to be involved in tumor progression. We previously reported that ISG15 expressed on nasopharyngeal carcinoma (NPC) cells and related to poor prognosis of patients with NPC. We further observed that ISG15 can be secreted by NPC cell and expressed on the macrophages in situ. However, the role of ISG15 in tumor-associated macrophages (TAMs) remains poorly understood. In the present study, we found that ISG15 treatment induces macrophages with M2-like phenotype, and the enhancement of NPC cell migration and tumorigenicity. Mechanically, ISG15-induced M2-like phenotype is dependent on the interaction with its receptor, LFA-1, and engagement of SRC family kinase (SFK) signal, and the subsequent secretion of CCL18. Blocking LFA-1, or SRC signal with small molecular inhibitors, or neutralizing with anti-CCL18 antibody can impede the activation of LFA-1-SFK-CCL18 axis in ISG15-treated macrophages. Clinically, ISG15+ CD163+ TAMs related to impaired survival of patients and advanced tumor stage of NPC. Furthermore, we found ISG15+ CD163+ macrophages inhibited antitumor CD8+ cells responses in NPC. Together, our findings suggested tumor cell-secreted ISG15, which acted as a tumor microenvironmental factor, induces M2-like phenotype, promoting tumor progression and suppression of cytotoxic T lymphocyte response.

Risk factors for recurrence after bowel resection for Crohn's disease.

BACKGROUND: Complications of Crohn's disease such as intestinal obstruction, fistula or perforation often need surgical treatment. Nearly 70%-80% patients with Crohn's disease would receive surgical treatment during the lifetime. However, surgical treatment is incurable for Crohn's disease. The challenge of recurrence postoperatively troubles both doctors and patients. Over 50% patients would suffer recurrence postoperatively. Some certain risk factors are associated with recurrence of Crohn's disease. AIM: To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn's disease. METHODS: Patients diagnosed Crohn's disease and received intestinal resection between April 2007 and December 2013 were included in this study. Data on the general demographic information, preoperative clinical characteristics, surgical information, postoperative clinical characteristics were collected. Continuous data are expressed as median (inter quartile range), and categorical data as frequencies and percentages. Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence, then log-rank test was applied to test the homogeneity of those clinical variables. Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence. RESULTS: A total of 64 patients were included in this study. The median follow-up time for the patients was 17 (9.25-25.75) mo. In this period, 41 patients (64.1%) had endoscopic recurrence or clinical recurrence. Endoscopic recurrence occurred in 34 (59.6%) patients while clinical recurrence occurred in 28 (43.8%) patients, with the interval between the operation and recurrence of 13.0 (8.0-24.5) months and 17.0 (8.0-27.8) mo, respectively. In univariate analysis, diagnosis at younger age (P < 0.001), disease behavior of penetrating (P = 0.044) and preoperative use of anti-tumor necrosis factor (TNF) (P = 0.020) were significantly correlated with endoscopic recurrence, while complication with perianal lesions (P = 0.032) and preoperative use of immunomodulatory (P = 0.031) were significantly correlated with clinical recurrence. As to multivariate analysis, diagnostic age (P = 0.004), disease behavior (P = 0.041) and preoperative use of anti-TNF (P = 0.010) were independent prognostic factors for endoscopic recurrence, while complication with perianal lesions (P = 0.023) was an independent prognostic factor for clinical recurrence. CONCLUSION: Diagnostic age, disease behavior, preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn's disease.

Overexpression of G protein-coupled receptor 31 as a poor prognosticator in human colorectal cancer.

AIM: To investigate the expression of G protein-coupled receptor 31 (GPR31) and its clinical significance in human colorectal cancer (CRC). METHODS: To determine the association between the GPR31 expression and the prognosis of patients, we obtained paraffin-embedded pathological specimens from 466 CRC patients who underwent initial resection. A total of 321 patients from the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were included as a training cohort, whereas 145 patients from the Sixth Affiliated Hospital of Sun Yat-sen University from January 2007 to November 2008 were included as a validation cohort. We examined GPR31 expression levels in CRC tissues from two independent cohorts via immunohistochemical staining. All patients were categorized into either a GPR31 low expression group or a GPR31 high expression group. The clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group were compared. RESULTS: We compared the clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group. Significant differences were observed in the number of patients in pM classification between patients in the GPR31 low expression group and GPR31 high expression group (P = 0.007). The five-year survival and tumor-free survival rates of patients were 84.3% and 82.2% in the GPR31 low expression group, respectively, and both rates were 59.7% in the GPR31 high expression group (P < 0.05). Results of the Cox proportional hazard regression model revealed that GPR31 upregulation was associated with shorter overall survival and tumor-free survival of patients with CRC (P < 0.05). Multivariate analysis identified GPR31 expression in colorectal cancer as an independent predictive factor of CRC patient survival (P < 0.05). CONCLUSION: High GPR31 expression levels were found to be correlated with pM classification of CRC and to serve as an independent predictive factor of poor survival of CRC patients.

CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways.

Papillary thyroid carcinoma (PTC) is the one of the most common types of endocrine cancer and has a heterogeneous prognosis. Tumors from patients with poor prognosis may differentially express specific genes. Therefore, an analysis of The Cancer Genome Atlas (TCGA) database was performed and revealed that cytokine receptor-like factor 1 (CRLF1) may be a potential novel target for PTC treatment. The objective of the current study was to explore the expression of CRLF1 in PTC and to investigate the main functions and mechanisms of CRLF1 in PTC. PTC tissues exhibited higher CRLF1 expression at both the mRNA and protein levels than it did with normal thyroid tissues. High CRLF1 levels were associated with aggressive clinicopathological features and poor disease-free survival rates. By using loss-of-function and gain-of-function assays, we found that CRLF1 not only increased cell migration and invasion in vitro but also promoted tumor growth both in vitro and in vivo. In addition, CRLF1 induced epithelial-mesenchymal transitions. Overexpression of CRLF1 activated the ERK1/2 and AKT pathways. The oncogenic effects induced by CRLF1 were suppressed by treating the cells with the MEK inhibitor U0126 or the AKT inhibitor MK-2206. These results suggest that CRLF1 enhances cell proliferation and metastasis in PTC and thus may therefore be a potential therapeutic target for PTC.

Overexpression of Nogo receptor 3 (NgR3) correlates with poor prognosis and contributes to the migration of epithelial cells of nasopharyngeal carcinoma patients.

Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines. Among these genes, Nogo receptor 3 (NgR3), which was originally identified in the nervous system and plays a role in nerve development and regeneration, was inappropriately overexpressed in NPC cells and tissues. Immunohistochemical analysis demonstrated that the overexpression of NgR3 was correlated with poor prognosis in NPC patients. Overexpression of NgR3 promoted, and knocking down NgR3 inhibited, NPC cell migration and invasion in vitro and metastasis in vivo. The ability of NgR3 to promote cell migration was triggered by the downregulation of E-cadherin and enhanced cytoskeletal rearrangement and cell polarity, which were correlated with the activation of focal adhesion kinase (FAK). Collectively, NgR3 is a novel indicator of poor outcomes in NPC patients and plays an important role in driving the progression of NPC. These results suggest a potential link between the nervous system and NPC progression. KEY MESSAGES: Genes involved in the neuronal biological process are enriched in nasopharyngeal carcinoma. Overexpression of NgR3 correlates with poor prognosis of nasopharyngeal carcinoma. NgR3 promotes NPC cell migration by downregulating E-cadherin. NgR3 promotes NPC cell polarity and enhances the formation of NPC cell pseudopodia by activating FAK/Src pathway.

Novel chimeric transcript RRM2-c2orf48 promotes metastasis in nasopharyngeal carcinoma.

Recently, chimeric transcripts have been found to be associated with the pathogenesis and poor prognosis of malignant tumors. Through our preliminary experiment, a novel chimeric transcript called chimeric transcript RRM2-c2orf48 was detected in C666-1, a classical cell line of human nasopharyngeal carcinoma (NPC). Therefore, the objective of this study was to demonstrate the existence and expression of novel chimeric transcript RRM2-c2orf48 and to explore the main functions and mechanisms of RRM2-c2orf48 in NPC. In this study, the expression of RRM2-c2orf48 was evaluated in NPC cells and specimens. Effects of RRM2-c2orf48 on migration and invasive capacities were detected in vivo and vitro. Moreover, ways in which RRM2-c2orf48 increases the invasive capacities of NPC were explored. As a result, the presence of novel chimeric transcript RRM2-c2orf48 was confirmed in C666-1 by RT-PCR and sequencing, and it was a read-through between RRM2 and c2orf48 through the transcription of interchromosome. Higher expressions of novel RRM2-c2orf48 were detected in NPC cell lines and NPC tissue specimens relative to the controls and its expression was be statistically relevant to TNM staging. High level of RRM2-c2orf48 could increase the migration and invasive capacities of NPC cells, potentially as a result of NPC cell epithelial-mesenchymal transition. RRM2-c2orf48 could also enhance resistance of chemotherapy. In vivo, RRM2-c2orf48 could enhance lung and lymph node metastasis in nude mice. These results demonstrate that high levels of RRM2-c2orf48 expression may be a useful predictor of NPC patients of metastatic potency, presenting potential implications for NPC diagnosis and therapy.

Postoperative immune response and surgical stress in selective neck dissection: Comparison between endoscopically assisted dissection and open techniques in cT1-2N0 oral squamous cell carcinoma.

BACKGROUND: Endoscopically assisted selective neck dissection (SND) has recently been applied in clinical N0 cases of oral squamous cell carcinoma (OSCC). However, nothing is known of the immune response after surgery. METHODS: A total of 60 patients with cT1-2N0 OSCC randomly underwent endoscopically assisted SND and open operations. The serum levels of IL-6, IL-8, IL-10, IL-1b, TNF-a, CRP, cortisol, ACTH, and growth hormone were analyzed before the start of the surgery (T0) and at 2 (T1), 6 (T2), 24 (T3), and 72 h (T4) after surgery. RESULTS: A total of 31 patients were randomized for endoscopic SND, whereas 29 underwent open procedures. The release of IL-6, IL-10 and CRP was significantly lower in the endoscopic group than in the open surgery group (p < 0.05), and cortisol levels were also lower in the endoscopic group (p < 0.05). CONCLUSIONS: Endoscopic SND could effectively provide lower inflammatory responses and surgical stress, reducing peri-operative trauma and accelerating recovery.

Prognostic value of the C-reactive protein/albumin ratio in patients with laryngeal squamous cell carcinoma.

PURPOSE: The present study was designed to retrospectively evaluate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in laryngeal squamous cell carcinoma (LSCC). METHODS: One hundred and twenty-nine newly diagnosed LSCC patients admitted between May 2006 and October 2011 were retrospectively reviewed. Their serum CRP and ALB were quantified preoperatively. The relationship between the CRP/ALB ratio and the clinicopathologic features was analyzed. Receiver operating characteristic curve was used to calculate the prognostic value of the CRP/ALB ratio. Then, the Cox proportional hazards model was used in univariate and multivariate analyses to identify significant prognostic factors associated with disease-free survival and overall survival. RESULTS: The cutoff value for CRP/ALB ratio was 0.047. An elevated CRP/ALB ratio was significantly associated with nodal metastasis, late disease stage, and recurrence. Also, high values of CRP/ALB ratio were significant predictors for poor overall survival and disease-free survival on multivariate analysis. CONCLUSION: Pretreatment CRP/ALB ratio may be a significant prognostic marker in LSCC.

Endoscope-assisted extracapsular dissection of benign parotid tumors through a single cephaloauricular furrow incision versus a conventional approach.

BACKGROUND: A few modified approaches have been reported for performing endoscope-assisted dissections of benign parotid tumors, but none that use incisions totally hidden in a natural furrow. This study evaluated the feasibility of performing endoscope-assisted extracapsular dissections of benign parotid tumors using a single cephaloauricular furrow incision. METHODS: Forty-six patients with benign parotid superficial lobe tumors were randomly divided into two groups: an endoscope-assisted (21 patients) group or a conventional (25 patients) surgery group. Perioperative and postoperative outcomes of the patients were evaluated, including the maximum diameter of the tumors, length of the incision, operating time, estimated blood loss during the operation, amount and duration of drainage, satisfaction scores based on the cosmetic results, perioperative complications, and follow-up information. RESULTS: The diameters of the tumors were comparable between the groups, and all operations were successfully performed as planned. The mean length of the incision in the endoscope-assisted group (3.6 ± 0.5 cm) was significantly shorter than that in the conventional group (9.1 ± 1.9). Meanwhile, the intraoperative blood loss, amount of drainage, perioperative complications, and cosmetic outcomes were all improved in the endoscope-assisted group. No tumor recurrence was found during 11-40 months of follow-up. CONCLUSIONS: Cephaloauricular furrow incisions were totally and naturally hidden in this procedure. Endoscope-assisted extracapsular dissections of benign parotid tumors via a small cephaloauricular furrow incision were found to be feasible and reliable, providing a minimally invasive approach and a satisfactory appearance.

Antibodies Against Epstein-Barr Virus Glycoprotein gp42 for the Diagnosis of Nasopharyngeal Carcinoma.

BACKGROUND: Assessment of immunoglobulin A (IgA) antibody responses to Epstein-Barr virus (EBV) antigen is important for the early diagnosis of nasopharyngeal carcinoma (NPC). EBV glycoprotein gp42 has been shown to play an essential role in membrane fusion with B cells. The aim of the present study was to assess whether the antibodies to EBV glycoprotein gp42 in serum could be a novel marker for diagnosis of NPC. METHODS: EBV glycoprotein gp42 expressed in the recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to gp42 in serum. The blood samples were obtained from 406 participants (n = 208 patients with NPC and 198 healthy controls). Receiver operating characteristics (ROC) was used to calculate diagnostic accuracy. RESULTS: The ROC curves showed that IgA-gp42 ELISA had a sensitivity of 76.4%, specificity of 78.3% and an area under the curve (AUC) of 0.856 (95% CI, 0.82 - 0.891) to diagnose NPC. Furthermore, gp42 maintained diag- nostic capacity in NPC patients who were IgA-viral capsid antigen (VCA) negative (87.5%, 64.1% and 0.844 [95% CI, 0.776 - 0.912]). Combining gp42 and VCA improved the diagnostic capacity compared with the individual tests (89.9%, 94.4% and 0.973 [95% CI, 0.959 - 0.9871). CONCLUSIONS: The EBV glycoprotein complex gp42 acts as a novel biomarker for diagnosis of NPC and improves identification of patients with VCA-negative NPC.

Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma.

To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort (n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort (n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls (p < 0.001). In the training cohort, the IgA-gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC.

The experience of gasless endoscopic-assisted thyroidectomy via the anterior chest approach for Graves' disease.

The aim of this study was to evaluate the safety, feasibility, effectiveness, and cosmesis of a gasless endoscopic-assisted thyroidectomy via the anterior chest in patients with Graves' disease. We retrospectively reviewed 38 patients with Graves' disease treated with thyroidectomy from November 2007 to June 2015. We analyzed clinical characteristics of patients, type of operation, operative indications, operative duration, length of postoperative hospital stay, and postoperative complications. The thyroidectomies were classified as total thyroidectomy (n = 12) or near-total thyroidectomy with a remnant of <1 g (n = 26). Surgical indications were recurrence after antithyroid drugs (ATDs) and unwillingness to undergo radioiodine therapy (n = 27), local compressive symptoms (n = 2), adverse drug reactions to ATDs (n = 5), and patient's preference (n = 4). Mean resection weight was 71.7 ± 16.2 g (range 44-109 g), mean operative duration 87.7 ± 17.3 min (range 66-136 min), intraoperative blood loss 70.6 ± 11.3 mL (range 43-92 mL), and drainage was 42.0 ± 8.5 mL (range 20-62 mL). Temporary postoperative recurrent laryngeal nerve palsy and temporary hypoparathyroidism occurred in 3 cases (7.89 %) each. Mean hospital stay was 2.5 ± 0.3 days (range 2-4 days). There was no recurrence of hyperthyroidism over the follow-up period of for 68.1 ± 5.6 months (range 6-89 months). All patients were satisfied with their cosmetic results. Gasless endoscopic-assisted thyroidectomy via the anterior chest approach for Graves' disease is a safe, feasible, and effective and provides an excellent cosmetic outcome procedure. It is a valid option in appropriately selected patients.