Transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation: a clinicopathologic study of 5 cases and review of the literature

To date, only 16 cases of transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation have been reported in the literature. We reviewed the clinicopathologic features of 5 cases of endometrial carcinoma with transitional cell differentiation. The mean age was 68 years, and all patients presented with postmenopausal bleeding. Macroscopically, the tumors were intracavitary and friable. Microscopically, the tumors were composed of tightly packed papillary structures with thin fibrovascular cores, resembling a transitional cell carcinoma of the urinary tract. One tumor showed exclusively transitional cell differentiation, whereas the remaining 4 neoplasms showed that the transitional cell carcinoma was admixed with a variable proportions of endometrioid adenocarcinoma. Four cases were in FIGO stage IB, whereas the remaining tumor infiltrated the uterine cervix (FIGO stage IIB). Immunoreactivity was typical of müllerian derivatives (cytokeratin 7 positive, cytokeratin 20 negative). p16 protein was positive in all cases, but human papillomavirus DNA was not detected in any of the tumors. None of the patients developed local recurrence or distant metastases, even though there are too few cases of transitional cell carcinoma of the endometrium reported to make any statistically valid conclusions about response to therapy and prognosis. Transitional cell carcinoma is an unusual variant of endometrial carcinoma, with distinctive histologic and immunophenotypic features. Identification of this variant broadens the morphological spectrum of epithelial neoplasms of the endometrium.     

Schneiderian Membrane Thickness and Clinical Implications for Sinus Augmentation: A Systematic Review and Meta‐Regression Analyses

Background: Schneiderian membrane thickness (SMT) has been regarded as a key factor for influencing membrane perforation, which may jeopardize the final clinical outcome of sinus augmentation. Hence, this systematic review aims at studying the mean SMT and further investigating patient‐related factors that may affect SMT. As a secondary goal, the association between SMT and membrane perforation rate was studied. Methods: Three independent reviewers in several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register databases, conducted electronic and manual literature searches. This review was written and conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) and MECIR (Methodological Expectations of Cochrane Intervention Reviews) guidelines. Quantitative assessment was performed for articles that met the inclusion criteria to investigate the mean SMT, its contributing factors, and the influence on membrane damage and surgical complications. Results: Thirty‐one studies that reported maxillary SMT were considered for qualitative analysis. Nineteen were further meta‐analyzed. Overall mean ± SE SMT was 1.17 ± 0.1 mm (95% confidence interval [CI] = 0.89 to 1.44). Although mean SMT for the three‐dimensional radiography (3DR) group was 1.33 mm (95% CI = 1.06 to 1.60), for the histology group, it was 0.48 mm (95% CI = 0.12 to 1.1). Random‐effects model showed that, although there is a trend for thicker SMT as determined using 3DR compared with histologic analysis, such difference did not reach statistical significance (P = 0.15). Also, regression analyses demonstrated that the variables periodontitis (P = 0.13) and smoking (P = 0.11) showed thicker SMT. Inconclusive data were obtained when correlating SMT and perforation rate, although it seems that thicker SMT might be more prone to perforation (P = 0.14). Conclusions: SMT is, on average, 1 mm in patients seeking sinus augmentation. Three‐dimensional technologies overestimate approximately 2.5 times SMT when compared with histologic analysis. Periodontitis and smoking may result in thickening of the sinus membrane. However, current data were inconclusive to link SMT to the rate of membrane damage.     

A multicentric European study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens.

This study was designed to assess intraobserver and interobserver agreement in the diagnosis of 56 endometrial specimens by five European expert gynecologic pathologists using the WHO classification and to establish which histologic features are significantly associated with each classification category. The seven categories were simple hyperplasia, complex hyperplasia, atypical hyperplasia, well-differentiated adenocarcinoma, proliferative endometria, secretory endometria, and other. Slides were reviewed twice for diagnosis, with accompanying evaluation of a checklist of histologic features. These seven categories were eventually reduced to four and three for the purposes of data analysis. The four modified diagnostic categories consisted of hyperplasia (previously simple hyperplasia and complex hyperplasia), atypical hyperplasia, well-differentiated adenocarcinoma, and cyclical endometrium (previously proliferative, secretory, and other). The three diagnostic categories consisted of hyperplasia, endometrioid neoplasia (previously atypical hyperplasia and well-differentiated adenocarcinoma), and cyclical endometrium. Intraobserver and interobserver agreement was assessed using the percentage agreement and kappa statistics. The associations among the various histologic features and diagnoses was analyzed using multiple logistic regression to identify those features that were useful for distinguishing diagnostic categories. When using seven categories, kappa values ranged from 0.53 to 0.74 (percentage agreement, 61-79%) and from 0.33 to 0.59 (percentage agreement, 43-63%) for intraobserver and interobserver agreement, respectively. When using four categories, kappa values ranged from 0.68 to 0.73 (percentage agreement, 77-80%) and from 0.39 to 0.64 (percentage agreement, 54-73%) for intraobserver and interobserver agreement, respectively. When using three categories, kappa values ranged from 0.70 to 0.83 (percentage agreement, 80-89%) and from 0.55 to 0.73 (percentage agreement, 70-82%) for intraobserver and interobserver agreement, respectively. Data were analyzed in each diagnostic category. When using four or three diagnostic categories, the mean intraobserver and interobserver agreements varied less between categories and achieved higher values, with smaller 95% confidence intervals. The mean percentage agreement was lowest for complex hyperplasia and for atypical hyperplasia. For distinguishing cyclical endometrium versus hyperplasia, the useful histologic feature was glandular crowding. For hyperplasia versus atypical hyperplasia and for hyperplasia versus endometrioid neoplasia, the useful features were nuclear enlargement, nuclear pleomorphism, vesicular chromatin, and nucleoli, but of these, only nuclear pleomorphism achieved substantial mean intraobserver and interobserver agreements. For discriminating atypical hyperplasia from well-differentiated adenocarcinoma, the only useful feature was stromal alterations, which achieved only fair mean intraobserver and interobserver agreements. In summary, in endometrial biopsy or curettage specimens, the lack of agreement in the diagnoses of complex hyperplasia and atypical hyperplasia and the lack of reproducibility in the recognition of the histologic feature of stromal alterations to differentiate atypical hyperplasia from well-differentiated adenocarcinoma suggest that the histologic classification should be simplified by including a combined category for simple and complex hyperplasia, called hyperplasia, and a combined category for atypical hyperplasia and well-differentiated adenocarcinoma, called endometrioid neoplasia. Diagnoses of hyperplasia and endometrioid neoplasia are highly reproducible between observers from different institutions. Glandular crowding is the best histologic feature to differentiate cyclical endometrium from hyperplasia, whereas nuclear pleomorphism is the reproducible cytologic feature to differentiate hyperplasia from endometrioid neoplasia.     

Intrahepatic bile duct and portal vein anatomy revisited

Seventeen normal cadaver livers were studied to assess the anatomic relationship of bile ducts to portal veins. The common bile duct, main portal vein, and hepatic artery were cannulated and injected with air, dilute contrast medium, and mineral oil, respectively. The livers were placed in anatomic position and examined with computed tomography. In the lateral segment of the left hepatic lobe, the bile ducts were anterior to the portal vein in seven cases, posterior in seven, and tortuous (ie, both anterior and posterior) in three. In the medial segment of the left lobe, the bile ducts were anterior in four cases, posterior in four, tortuous in three, and not seen in six. In the right lobe, the bile ducts were anterior in nine cases, posterior in five, tortuous in one, and not seen in two. In the porta hepatis, the bile ducts were anterior in ten cases, posterior in one, tortuous in five, and not seen in one. Histologic findings confirmed the anterior and posterior location of the bile ducts relative to the portal veins. These findings contradict the commonly held view of intrahepatic bile ducts being anterior to the portal vein and are clinically significant for techniques such as bile duct drainage.     

Reticulocyte hemoglobin content for the diagnosis of iron deficiency

SUMMARY: Identification of iron deficiency (ID) is essential to initiate early treatment to prevent long-term systemic complications of ID anemia. This study was undertaken to evaluate the efficiency of the parameter reticulocyte hemoglobin content (CHr) compared with other laboratory parameters in the assessment of ID in a pediatric population. Blood samples were obtained for 237 children who received routine pediatric care visits in a primary care clinic (mean age: 63.7 mo; male:female ratio: 1.08:1). A multiple stepwise logistic regression analysis identified CHr as the most accurate marker independently associated to ID. A CHr cutoff value of 25 pg (sensitivity: 94%; specificity: 80%) proved an optimal performance predicting ID. Therefore, we conclude that the hematologic parameter CHr constitutes a valuable screening tool for the identification of ID with or without anemia in childhood.     

增效联磺片的体外溶出度和体内生物利用度

建立了测定体外溶出介质中磺胺嘧啶(SD)、磺胺甲噁唑(SMZ)和甲氧苄啶(TMP)及血浆中SD,SMZ,TMP和两个代谢产物N⁴-acetyl-SD和N⁴-acetyl-SMZ的反相高效液相色谱法,并对市售两种增效联磺片(片剂A和B)进行了体外溶出度和人体内生物利用度的研究。体外溶出度实验表明:两种片剂相同主药的T⁵⁰差异非常显著(P<0.001),片剂A主药的溶出比B快。生物利用度试验表明:片剂B相对于A的口服吸收分数为0.73(SD),0.78(SMZ)和0.83(TMP),口服片剂后各主药的体内过程符合表观一级吸收和一级消除的单室模型。     

Identification of core genes in ovarian cancer by an integrative meta-analysis

Background

Epithelial ovarian cancer is one of the most ?severe public health threats in women. Since it is still challenging to screen in early stages, identification of core genes that play an essential role in epithelial ovarian cancer initiation and progression is of vital importance.

Results

Seven gene expression datasets (GSE6008, GSE18520, GSE26712, GSE27651, GSE29450, GSE36668, and GSE52037) containing 396 ovarian cancer samples and 54 healthy control samples were analyzed to identify the significant differentially expressed genes (DEGs). We identified 563 DEGs, including 245 upregulated and 318 downregulated genes. Enrichment analysis based on the gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the upregulated genes were significantly enriched in cell division, cell cycle, tight junction, and oocyte meiosis, while the downregulated genes were associated with response to endogenous stimuli, complement and coagulation cascades, the cGMP-PKG signaling pathway, and serotonergic synapse. Two significant modules were identified from a protein-protein interaction network by using the Molecular Complex Detection (MCODE) software. Moreover, 12 hub genes with degree centrality more than 29 were selected from the protein-protein interaction network, and module analysis illustrated that these 12 hub genes belong to module 1. Furthermore, Kaplan-Meier analysis for overall survival indicated that 9 of these hub genes was correlated with poor prognosis of epithelial ovarian cancer patients.

Conclusion

The present study systematically validates the results of previous studies and fills the gap regarding a large-scale meta-analysis in the field of epithelial ovarian cancer. Furthermore, hub genes that could be used as a novel biomarkers to facilitate early diagnosis and therapeutic approaches are evaluated, providing compelling evidence for future genomic-based individualized treatment of epithelial ovarian cancer.