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Objective: In order to avoid the misdiagnosis of thyroid diseases, we need to discuss the clinical features and diagnostic methods of cervical esophageal cancer and Zenker's diverticulum. Methods: The clinical and laboratory data of seven cases were reviewed retrospectively, and in all cases, esophageal-related diseases were misdiagnosed as thyroid diseases preoperatively. Among them, two cases were cervical esophageal cancer metastasized to thyroids but initially, they were misdiagnosed as thyroid cancer. The other five cases were Zenker's diverticulum, but were originally diagnosed as nodular goiter, and two out of the five cases were found with calcification. They were all detected by ultrasound examination without any clinical feature of esophageal diseases. Previous literatures only reported five cases of thyroid metastasis and three cases of Zenker's diverticulum. Results: In both cases where cervical esophageal cancer metastasized to thyroid, anterior cervical neoplasm biopsy and surgical removal were performed followed by postoperative radiotherapy and chemotherapy. Both patients died from esophageal cancers in 7 and 15 months postoperatively. All five cases of Zenker's diverticulum received excision and repair without any postoperative complication or recurrence in the following 2 to 7 years. Conclusions: Cervical esophageal cancer and Zenker's diverticulum may be misdiagnosed as thyroid disease. Careful and comprehensive diagnostic tests would be required to avoid misdiagnosis. [ABSTRACT FROM AUTHOR]

Background: Breast ductal cancer in situ (DCIS) can recur or progress to invasive ductal cancer (IDC), and the interim stage include DCIS with microinvasion (DCIS-Mi). In this article, we attempt to study the study the differences of clinicopathological features, imaging data, and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and IDC. Methods: In this retrospective study, we attempt to compare the clinicopathological features, immunohistochemical results and imaging data of 866 patients (included 73 DCIS, 72 DCIS-Mi, and 721 IDC). Results: Patients with DCIS and DCIS-Mi were younger than those with IDC (P = 0.007). DCIS and DCIS-Mi often happened in premenopausal women while IDC was opposite (P <0.001). The incidence of IDC with node-positive was significantly higher than it in DCIS and DCIS-Mi (P <0.001). We also observed that the Her2-positive was more often found in patients with pure DCIS compared to those with DCIS-Mi and DCIS-I (P <0.001). There was a significant difference between the four subgroups (Luminal-A, Luminal-B, ERBB2+, Basal-like) from DCIS, DCIS-Mi, and IDC (P <0.001). Basal-like patients were fewer than other subgroups in DCIS, DCIS-Mi, and IDC. The incidence of the first performance of ultrasound (catheter winded and nodular mass) and mammography (nodular mass) had significantly difference among patients with DCIS, DCIS-Mi, and IDC (P <0.001). Conclusions: Different clinicopathological, immunohistochemical, and imaging features among DCIS, DCIS-Mi, and IDC indicate that they are distinct entities. A larger sample size is needed for further study. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells, migrating cancer stem cells and chemoradioresistant cancer stem cells, playing different roles in cancer initiation and progression. Here we propose a new concept "horizontal hierarchy of cancer stem cells" to distinguish them from vertical hierarchy cancer stem cells, cancer transient-amplifying cells and cancer differentiated cells, and summarize our current understanding of these subsets of cancer stem cells with the aim to open up novel therapeutic strategies for cancer based on this understanding. [ABSTRACT FROM AUTHOR]

Background: Clinicians are confronted with an increasing number of patients with thyroid nodules. Reliable preoperative diagnosis of thyroid nodules remains a challenge because of inconclusive cytological examination of fine-needle aspiration biopsies. Although molecular analysis of thyroid tissue has shown promise as a diagnostic tool in recent years, it has not been successfully applied in routine clinical use, particularly in Chinese patients., Methods: Whole-transcriptome sequencing of 19 primary papillary thyroid cancer (PTC) samples and matched adjacent normal thyroid tissue (NT) samples were performed. Bioinformatics analysis was carried out to identify candidate diagnostic genes. Then, RT-qPCR was performed to evaluate these candidate genes, and four genes were finally selected. Based on these four genes, diagnostic algorithm was developed (training set: 100 thyroid cancer (TC) and 65 benign thyroid lesions (BTL)) and validated (independent set: 123 TC and 81 BTL) using the support vector machine (SVM) approach., Results: We discovered four genes, namely fibronectin 1 (FN1), gamma-aminobutyric acid type A receptor beta 2 subunit (GABRB2), neuronal guanine nucleotide exchange factor (NGEF) and high-mobility group AT-hook 2 (HMGA2). A SVM model with these four genes performed with 97.0 % sensitivity, 93.8 % specificity, 96.0 % positive predictive value (PPV), and 95.3 % negative predictive value (NPV) in training set. For additional independent validation, it also showed good performance (92.7 % sensitivity, 90.1 % specificity, 93.4 % PPV, and 89.0 % NPV)., Conclusions: Our diagnostic panel can accurately distinguish benign from malignant thyroid nodules using a simple and affordable method, which may have daily clinical application in the near future.

Background: The purpose of this study was to evaluate the clinicopathologic and ultrasonographic (US) characteristics and establish an effective scoring system for predicting central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC)., Methods: A total of 498 patients with PTMC who underwent total thyroidectomy or lobectomy with therapeutic central lymph node dissection (CLND) were enrolled. Univariate and multivariate analyses were performed to find the independent predictors for CLNM based on clinicopathological and US characteristics. Using the standardized regression coefficient, a 10-point score system was constructed in line with these independent predictors. Then, the scoring system was evaluated for the diagnostic value in predicting CLNM., Results: Tumor location (the lower polo), tumor size (>5 mm), extrathyroidal extension, margin (no well-defined), display of enlarged lymph node, and contact of >25% with the adjacent capsule were independent predictors for CLNM. Verifying the scoring system, a cutoff value of 5 points was found to be the best prediction for CLNM, the sensitivity and specificity were 64.7 and 80.5%, respectively, and the positive and negative predictive values were 77.3 and 69.0%, respectively., Conclusions: The points≤5 could be considered as a low risk for CLNM, and the points>5 could be identified as a high risk for CLNM. More advanced diagnostic approaches and prophylactic CLND are needed for patients with the points>5.

Background: Luteimonas abyssi XH031(T), which was previously isolated from subseafloor environment of the South Pacific Gyre (SPG), was an aerobic, gram-negative bacterium, and was identified to be a novel species of the genus Luteimonas in the family of Xanthomonadaceae. The nutrients utilization and metabolic mechanisms of XH031(T) indicate its plasticity. In view of the above characteristics, its genome was sequenced, and an in-depth analysis of the XH031(T) genome was performed to elucidate its adaption to extreme ecological environment., Results: Various macromolecules including polysaccharide, protein, lipid and DNA could be degraded at low temperature by XH031(T) under laboratory conditions, and its degradation abilities to starch, gelatin and casein were considerably strong. Genome sequence analysis indicated that XH031(T) possesses extensive enzyme-encoding genes compared with four other Luteimonas strains. In addition, intricate systems (such as two-component regulatory systems, secretion systems, etc.), which are often used by bacteria to modulate the interactions of bacteria with their environments, were predicted in the genome of XH031(T). Genes encoding a choline-glycine betaine transporter and 99 extracellular peptidases featured with halophilicity were predicted in the genome, which might help the bacterium to adapt to the salty marine environment. Moreover, there were many gene clusters in the genome encoding ATP-binding cassette superfamily transporters, major facilitator superfamily transporters and cytochrome P450s that might function in the process of various substrate transportation and metabolisms. Furthermore, drug resistance genes harbored in the genome might signify that XH031(T) has evolved hereditary adaptation to toxic environment. Finally, the annotation of metabolic pathways of the elements (such as carbon, nitrogen, sulfur, phosphor and iron) in the genome elucidated the degradation of organic matter in the deep sediment of the SPG., Conclusions: The genome analysis showed that XH031(T) had genetic advantages to adapt to subseafloor environment. The material metabolism manifests that the strain may play an important ecological role in the biogeochemical cycle of the SPG, and various cold-adapted extracelluar enzymes produced by the strain may have significant value in application.

Background: South Pacific Gyre (SPG) is the largest and clearest gyre in the world, where the concentration of surface chlorophyll a and primary production are extremely low. Aquimarina longa SW024(T) was isolated from surface water of the SPG center. To understand how this bacterium could survive in this ultra-oligotrophic oceanic environment and its function in biogeochemical cycle, we sequenced the genome of A. longa SW024(T) and performed extensive genomic analyses., Methods: Genomic DNA was extracted and sequenced using Illumina Hiseq 2000 and Miseq platform. Genome annotation, genomic comparison and phylogenetic analyses were performed with the use of multiple bioinformatics tools like: BLAST+ 2.2.24, Glimmer3.0, RAST server, Geneious 4.8.5, ClustalW2 and MEGA5. Physiological and morphological features were tested by bacterial culture, electron microscopy, fluorescence microscopy and exopolysaccharides extraction., Results: Analysis of seven Aquimarina genomes and 30 other genomes of Flavobacteriaceae isolated from seawater showed that most of the strains had low DNA G + C contents, and Aquimarina had larger genomes than other strains. Genome comparison showed varying genomic properties among seven Aquimarina genomes, including genome sizes and gene contents, which may warrant their specific adaptive strategies. Genome of A. longa SW024(T) was further compared with the genomes of two other Aquimarina species which were also isolated from the SPG and A. longa SW024(T) appeared to have much more genes related to replication, recombination and repair. As a copiotroph, A. longa SW024(T) is long in length, and possesses large genome size and diverse transporters. However, it has also evolved many properties to survive in the oligotrophic marine environment. This bacterium grew better on solid medium than in liquid medium, suggesting it may be liable to attach to particle surfaces in order to survive in the nutrient-limiting environment. Gliding motility and the capacity to degrade various polymers possibly allow the bacterium to grow on detritus particles and use polymeric substances as carbon and energy sources. Moreover, genes related to carbon, nitrogen, and sulfur metabolisms were identified, which showed that A. longa SW024(T) might be involved in various elemental cycles., Conclusions: Genomic comparison of Aquimarina genus exhibits comprehensive capabilities of the strains to adapt to diverse marine environments. The genomic characteristics of A. longa SW024(T) reveal that it evolves various strategies to cope with both copiotrophic and ultra-oligotrophic marine environment, which provides a better understanding of the survival abilities of bacteria in prevalent and even extreme oceanic environments. Furthermore, carbon, nitrogen and sulfur utilization of A. longa SW024(T) may represent its potential functions in the global biogeochemical cycle.

Background: Gene expression profiling of breast cancers identifies distinct molecular subtypes that affect prognosis. The aim of this study was to determine whether features of tumors especially the risks of lymph node (LN) metastases differ among molecular subtypes., Methods: Subtypes were classified by immunohistochemical surrogates as luminal A, luminalHer2-, luminalHer2+, TNBC, and HER-2+. Data were obtained from an established, registered database of patients with invasive breast cancer treated at our hospital between July 2012 and October 2014. A total of 929 tumors were classifiable into molecular subtypes., Results: The distribution of subtypes was luminal A (24.2%), luminalHer2- (27.8%), luminalHer2+ (9.1%), TNBC (21.3%), and HER-2+ (17.5%). Marked differences in age, tumor size, extent of lymph node involvement, and grade were observed among subtypes. On univariate analysis, the LN positivity varied across subtypes with 33.6% in luminal A, 40.3% in luminalHer2-, 37.3% in luminalHer2+, 37.6% in TNBC, and 47.4 % in HER-2+ (p=0.201). There was no significant difference in LN positivity among subtypes. On multivariable analysis, grade and tumor size were independent predictors of LN positivity., Conclusions: Predictors of LN metastases include higher grade and larger tumor size. Even though breast cancer subtype is not a statistically significant predictor of LN positivity, this information may still be useful in selecting the appropriate therapy in clinical practice.

Background: Intestinal microbes play significant roles in fish and can be possibly used as probiotics in aquaculture. In our previous study, Flaviramulus ichthyoenteri Th78(T), a novel species in the family Flavobacteriaceae, was isolated from fish intestine and showed strong quorum quenching (QQ) ability. To identify the QQ enzymes in Th78(T) and explore the potential roles of Th78(T) in fish intestine, we sequenced the genome of Th78(T) and performed extensive genomic analysis., Results: An N-acyl homoserine lactonase FiaL belonging to the metallo-β-lactamase superfamily was identified and the QQ activity of heterologously expressed FiaL was confirmed in vitro. FiaL has relatively little similarity to the known lactonases (25.2 ~ 27.9% identity in amino acid sequence). Various digestive enzymes including alginate lyases and lipases can be produced by Th78(T), and enzymes essential for production of B vitamins such as biotin, riboflavin and folate are predicted. Genes encoding sialic acid lyases, sialidases, sulfatases and fucosidases, which contribute to utilization of mucus, are present in the genome. In addition, genes related to response to different stresses and gliding motility were also identified. Comparative genome analysis shows that Th78(T) has more specific genes involved in carbohydrate transport and metabolism compared to other two isolates in Flavobacteriaceae, both isolated from sediments., Conclusions: The genome of Th78(T) exhibits evident advantages for this bacterium to survive in the fish intestine, including production of QQ enzyme, utilization of various nutrients available in the intestine as well as the ability to produce digestive enzymes and vitamins, which also provides an application prospect of Th78(T) to be used as a probiotic in aquaculture.

Metastasis to the thyroid is extremely rare. There is a lack of awareness of and adequate preparation for this situation, especially in an individual without a past history of malignancy. We describe a rare case of a 61-year-old man in whom a primary distal esophageal carcinoma gave rise to a metastatic palpable mass in the thyroid gland. Palliative bilateral near-total thyroidectomy was performed with pathology showing squamous cell carcinoma and tracheostomy was carried out simultaneously due to airway compression with related symptoms. A review of the literature only reveals 4 similar cases. Secondary neoplasm of the thyroid mimicking a primary malignant lesion is seldom encountered, however, in order to make appropriate treatment, the most critical problem is to distinguish the difference between the above two and the final diagnosis can only be confirmed on pathologic examination. Although the prognosis of thyroid metastasis is commonly felt to be poor, improvement of living quality and prolongation of survival may be obtained in such patients through correct diagnosis and treatment.

Background: Competition between bacteria for habitat and resources is very common in the natural environment and is considered to be a selective force for survival. Many strains of the genus Pseudoalteromonas were confirmed to produce bioactive compounds that provide those advantages over their competitors. In our previous study, P. flavipulchra JG1 was found to synthesize a Pseudoalteromonas flavipulchra antibacterial Protein (PfaP) with L-amino acid oxidase activity and five small chemical compounds, which were the main competitive agents of the strain. In addition, the genome of this bacterium has been previously sequenced as Whole Genome Shotgun project (PMID: 22740664). In this study, more extensive genomic analysis was performed to identify specific genes or gene clusters which related to its competitive feature, and further experiments were carried out to confirm the physiological roles of these genes when competing with other microorganisms in marine environment., Results: The antibacterial protein PfaP may also participate in the biosynthesis of 6-bromoindolyl-3-acetic acid, indicating a synergistic effect between the antibacterial macromolecule and small molecules. Chitinases and quorum quenching enzymes present in P. flavipulchra, which coincide with great chitinase and acyl homoserine lactones degrading activities of strain JG1, suggest other potential mechanisms contribute to antibacterial/antifungal activities. Moreover, movability and rapid response mechanisms to phosphorus starvation and other stresses, such as antibiotic, oxidative and heavy metal stress, enable JG1 to adapt to deleterious, fluctuating and oligotrophic marine environments., Conclusions: The genome of P. flavipulchra JG1 exhibits significant genetic advantages against other microorganisms, encoding antimicrobial agents as well as abilities to adapt to various adverse environments. Genes involved in synthesis of various antimicrobial substances enriches the antagonistic mechanisms of P. flavipulchra JG1 and affords several admissible biocontrol procedures in aquaculture. Furthermore, JG1 also evolves a range of mechanisms adapting the adverse marine environment or multidrug rearing conditions. The analysis of the genome of P. flavipulchra JG1 provides a better understanding of its competitive properties and also an extensive application prospect.

Background: To confirm whether clinical and biochemical parameters or Hashimoto's thyroiditis (HT) could predict the risks of malignancy among subjects who underwent thyroidectomy, as well as to determine the influence of HT on the biological behavior of papillary thyroid cancer (PTC)., Methods: A total of 2,052 patients who underwent initial thyroidectomy were enrolled between June 2006 and August 2008. Serum free T4, free T3, thyrotropin (TSH), thyroglobulin, thyroglobulin antibody, antimicrosomal antibody, tumor-associated status, and thyroid disorders were documented., Results: Binary logistic regression analysis was performed to define the risk predictors for thyroid cancer. Finally, calcification, HT, TSH, and age, were entered into the multivariate model. Multivariate logistic regression analysis revealed the risk of thyroid cancer increases in parallel with TSH concentration within normal range, and the risk for malignancy significantly increased with serum TSH 1.97-4.94 mIU/L, compared with TSH less than 0.35 mIU/L (OR = 1.951, 95% CI = 1.201-3.171, P = 0.007). Increased risks of thyroid cancer were also detected among the patients with HT (OR = 3.732, 95% CI = 2.563-5.435), and microcalcification (OR = 14.486, 95% CI = 11.374-18.449). The effects of HT on the aggressiveness of PTC were not observed in extrathyroidal invasion (P = 0.347), capsular infiltration (P = 0.345), angioinvasion (P = 0.512), and lymph node metastases (P = 0.634)., Conclusions: The risk of malignancy increases in patients with higher level TSH within normal range, as well as the presence of HT and microcalcification. No evidence suggests that coexistent HT alleviates the aggressiveness of PTC.

We report a case of continued twitching of the latissimus dorsi muscle following breast conservation therapy, along with immediate reconstruction with a latissimus dorsi miniflap, which continued despite several attempts at control including BTX-A percutaneous local injection, and was finally cured by delayed division of the thoracodorsal nerve via a small well-tolerated axillary incision.

Background: The optimal resection extent for papillary thyroid microcarcinoma (PTMC) remains controversial. The objective of the study was to investigate risk factors of bilateral PTMC and central lymph node metastasis (CLNM) to guide surgical strategies for PTMC patients., Methods: We retrospectively reviewed 211 PTMC patients who underwent total thyroidectomy (TT) and 122 clinical lymph node-negative (cN0) cases that underwent prophylactic central lymph node dissection (CLND) between 2010 and 2011. The frequency, pattern, and predictive factors for bilateral PTMC and CLNM in these patients were studied using univariate and multivariate analysis with respect to the following variables: age, gender, extrathyroidal extension (ETE), T stage, with Hashimoto thyroiditis (HT), tumor size and multifocality based on final pathology, and preoperative evaluation using ultrasonography (US)., Results: Fifty-four of 211 (25.6%) patients had bilateral PTMC. In multivariate analysis, multifocality (P < 0.001, OR = 23.900) and tumor size ≥7 mm (P = 0.014, OR = 2.398) based on US were independent predictive factors for bilateral PTMC which was also independently associated with multifocality (P < 0.001, OR = 29.657) and tumor size ≥7 mm (P = 0.005, OR = 2.863) based on final pathology. Among 122 cN0 patients who underwent prophylactic CLND, we found 49.2% of patients had CLNM. CLNM was independently associated with men, age <50 years and tumor size ≥7 mm based on final pathology or preoperative US., Conclusions: TT should be considered for PTMC patients who are found multifocality and tumor size ≥7 mm based on preoperative US. CLND need be considered in cN0 patients who are men, aged <50 years or tumor size ≥7 mm based on preoperative US.

Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells, migrating cancer stem cells and chemoradioresistant cancer stem cells, playing different roles in cancer initiation and progression. Here we propose a new concept "horizontal hierarchy of cancer stem cells" to distinguish them from vertical hierarchy cancer stem cells, cancer transient-amplifying cells and cancer differentiated cells, and summarize our current understanding of these subsets of cancer stem cells with the aim to open up novel therapeutic strategies for cancer based on this understanding.

Background: Emerging evidence has demonstrated that Neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated in multiple malignancies, including oesophagus cancer, and plays a critical role in tumorigenesis and progression. However, till now, little is known about the role of NGAL in human rectal cancer. Its association with clinicopathologic characteristics and expression of MMP-9, one of its target genes, has not been reported systematically in rectal cancer. Therefore, to further determine the potential involvement of NGAL in rectal cancer, we have evaluated the expression level of NGAL mRNA by real time RT-PCR, and further elucidated the correlation of NGAL mRNA expression with clinicopathologic features and MMP-9 in rectal cancer., Methods: 100 paired samples of rectal cancer and adjacent normal tissues obtained from inpatients undergoing surgical operation were allocated into two groups (cancer group and control group). The mRNA expression of NGAL and MMP-9 was determined by real-time RT-PCR. The association between their expression and clinicopathological characteristics of rectal cancer were analysised., Results: Among the 100 rectal cancers, 69 cases of NGAL mRNA up-regulation were observed. NGAL mRNA up-regulation was positively correlated with MMP-9 (rs = 0.393, p < 0.001). In rectal cancer, NGAL mRNA overexpression was significantly associated with depth of invasion (p = 0.028), lymph node metastasis (p = 0.009), venous involvement (p = 0.023) and advanced pTNM stage (p = 0.011)., Conclusion: In human rectal cancer, NGAL mRNA expression was elevated. NGAL mRNA up-regulation was correlated significantly with tumor progression and MMP-9 mRNA overexpression in rectal cancer, suggesting a more aggressive phenotype. NGAL could be used for rectal cancer characterization.

Background: Lymphangiogenesis has become a new research frontier in tumor metastasis since the discovery of reliable lymphatic markers that have allowed observation and isolation of lymphatic endothelium. Cyclooxygenase-2 (COX-2) has been reported to be involved in the critical steps in carcinogenesis. However, possible role of COX-2 in lymphangiogenesis and lymphatic metastasis is still poorly understood. In present study, we aimed to investigate the relationship between vascular endothelial growth factor-C (VEGF-C) and COX-2 in human breast cancer, and correlations with lymphangiogenesis and prognosis., Methods: Tissue samples of primary tumors from 70 patients undergoing intentionally curative surgical resections for breast cancer were immunohistochemically examined for VEGF-C, COX-2, and D2-40 expressions. The association between COX-2 and VEGF-C expressions and clinicopathological parameters as well as prognosis were analysised. To demonstrate the presence of proliferating lymphatic endothelial cells, 10 random cases with high LVD counts were selected for D2-40/Ki-67 double immunostaining., Results: A significant correlation was found between the expression of VEGF-C and COX-2 (r = 0.529, P < 0.001), and both elevated VEGF-C expression and elevated COX-2 expression were associated with higher lymph vessel density (LVD), lymph node metastasis and D2-40 positive lymphatic invasion (LVI) as well as worse disease free survival (DFS) and overall survival (OS) in a univariate analysis. In the double immunostain for the lymph vessel marker D2-40 and the proliferation marker Ki-67, the results confirmed Ki-67-positive nuclei in a proportion of lymph vessel endothelial cells., Conclusion: There is indeed lymphangiogenesis in breast cancer, the most compelling evidence being the presence of proliferating lymphatic endothelial cells. VEGF-C and COX-2 are coexpressed and significantly associated with lymphangiogenesis and prognosis in invasive breast cancer. Suggesting COX-2 may up-regulate VEGF-C expression and thus promote lymph node metastasis via lymphangiogenesis pathway in human breast cancer.