A new model using routinely available clinical parameters to predict significant liver fibrosis in chronic hepatitis B

Objective: We developed a predictive model for significant fibrosis in chronic hepatitis B (CHB) based on routinely available clinical parameters. Methods: 237 treatment-naïve CHB patients [58.4% hepatitis B e antigen (HBeAg)-positive] who had undergone liver biopsy were randomly divided into two cohorts: training group (n = 108) and validation group (n = 129). Liver histology was assessed for fibrosis. All common demographics, viral serology, viral load and liver biochemistry were analyzed. Results: Based on 12 available clinical parameters (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP, GGT and AFP), a model to predict significant liver fibrosis (Ishak fibrosis score ≥3) was derived using the five best parameters (age, ALP, AST, AFP and platelet). Using the formula log(index+1) = 0.025+0.0031(age)+0.1483 log(ALP)+0.004 log(AST)+0.0908 log(AFP+1)-0.028 log(platelet), the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index predicts significant fibrosis with an area under the receiving operating characteristics (AUROC) curve of 0.776 [0.797 for patients with ALT <2×upper limit of normal (ULN)] The negative predictive value to exclude significant fibrosis was 88.4%. This predictive power is superior to other non-invasive models using common parameters, including the AST/platelet/GGT/AFP (APGA) index, AST/platelet ratio index (APRI), and the FIB-4 index (AUROC of 0.757, 0.708 and 0.723 respectively). Using the PAPAS index, 67.5% of liver biopsies for patients being considered for treatment with ALT <2×ULN could be avoided. Conclusion: The PAPAS index can predict and exclude significant fibrosis, and may reduce the need for liver biopsy in CHB patients. © 2011 Seto et al.published_or_final_versio

High hepatitis B surface antigen levels predict insignificant fibrosis in hepatitis B e antigen positive chronic hepatitis B

INTRODUCTION: There is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB). METHODS: Serum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation. RESULTS: 140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT 1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p/= 25,000 IU/mL was independently associated with fibrosis score </= 1 (p=0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT </=2xULN, positive and negative predictive values for predicting fibrosis score </= 1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology. CONCLUSION: Among HBeAg-positive patients with ALT </=2xULN, high serum HBsAg levels can accurately predict fibrosis score </= 1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.published_or_final_versio

Paradoxical Impact of Two Folate Receptors, FRα and RFC, in Ovarian Cancer: Effect on Cell Proliferation, Invasion and Clinical Outcome

Despite being an essential vitamin, folate has been implicated to enhance tumor growth, as evidenced by reports on overexpression of folate receptor alpha (FRα) in carcinomas. The role of another folate transporter, reduced folate carrier (RFC), is largely unknown. This study investigated the roles of folate, FRα and RFC in ovarian cancers. We demonstrated FRα mRNA and protein overexpression and reduced RFC expression in association with FRα gene amplification and RFC promoter hypermethylation, respectively. FRα overexpression was associated with tumor progression while RFC expression incurred a favorable clinical outcome. Such reciprocal expression pattern was also observed in ovarian cancer cell lines. Folate was shown to promote cancer cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin expression. This effect was blocked after either stable knockdown of FRα or ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that, RFC can serve as a balancing partner of FRα and confer a protective effect in patients with high FRα-expressing ovarian carcinomas, as evidenced by their prolonged overall and disease-free survivals. In conclusion, we report on the paradoxical impact of FRα (putative oncogenic) and RFC (putative tumor suppressive) in human malignancies. FRα and RFC may potentially be explored as therapeutic target or prognostic marker respectively. We recommend caution and additional research on folate supplements in cancer patients. © 2012 Siu et al.published_or_final_versio

Practice Changes: 2014 WHO Classification of Tumours of Female Reproductive Organs

Symposium: Gynaecological Cance

Vaginal Intraepithelial Neoplasia

Vaginal squamous intraepithelial neoplasia (VaIN) is uncommon when comparing to the cervical or vulval counterparts. Almost all are caused by infection of human papillomaviruses (HPVs). Traditionally, VaIN was classified into grades I, II, and III, depending on the degree of involvement of the epithelium by the dysplastic cells. The 2013 Lower Anogenital Squamous Terminology (LAST) Standardization Project working group and the World Health Organization (WHO) 2014 classification recommend that lesions that are considered as condyloma and VaIN I should now be classified as low-grade squamous intraepithelial lesions (LSILs). LSIL is a morphological manifestation of transient, usually low-risk HPV infection. VaIN II/III lesions signify persistent infection by high-risk HPV and are considered precancerous; they should now be classified as high-grade squamous intraepithelial lesions (HSILs). The change in nomenclature reduces the problem of interobserver variability in assessing VaIN II and also classifies lesions into two biological and managerial groups. Histological assessment of problematic HSIL may be supported by using several immunohistochemical stains such as p16, ki-67, and ProEx C. Patients with persistent high-risk HPV infection are at an increased risk of recurrence and development into squamous cell carcinoma. Although many studies on HPV-associated lesions were done on the cervix, given the biological similarity between those in the vagina and other lower genital sites, it is conceivable that they can be regarded as closely related lesions even if not a single disease entity. Premalignant glandular lesions of the vagina are rare and a brief account will be given

Iatrogenic lesions of the female genital tract

Advances in management of obstetrical and gynaecological diseases mandate the practising pathologist to be familiar with various types of treatment-related pathology This review addresses iatrogenic pathology of the female genital tract under the following headings: pathology related to surgery, pathology related to contraception, pathology related to assisted reproduction, effects of tamoxifen therapy pathology of diethylstilbestrol, and effects of other specific drugs. © 2003 Elsevier Science Ltd.link_to_subscribed_fulltex

Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: A review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy

Uterine smooth muscle tumors are classified according to their morphologic features that include architecture, growth pattern, cellular characteristics and constituents of the intercellular stroma. While terminologies used for the pathologic diagnosis of various subtypes may be eloquent and histologically accurate, some of these are confusing for the clinician and may also be open to interpretation by different pathologists: the labeling of atypical leiomyomas epitomizes this intricate system. Clinically, it is probably more useful to classify them as either tumors with or tumors without recurrent and/or metastatic potential. The term "atypical leiomyoma" has been used to label tumors that have a low risk of recurrence and is synonymous with benign tumors. The latter are known variously as leiomyoma with bizarre nuclei, symplastic leiomyoma, or pleomorphic leiomyoma. Variants of benign uterine smooth muscle tumors, such as mitotically active leiomyoma, cellular and highly cellular leiomyoma, epithelioid leiomyoma, and myxoid leiomyoma each have distinctive hallmarks that enable subclassification. Nevertheless, they may occasionally possess one or more unusual features that are cause for alarm. Tumors that have a dissecting growth pattern, with or without extrauterine extension, may mimic malignancy both grossly and microscopically. The current review discusses the pathologic diagnosis of and terminology applied to selected variants of uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas with emphasis on unusual reported features that may indicate malignancy. This includes an update on uterine smooth muscle tumor of uncertain malignant potential (STUMP), intravenous leiomyomatosis, benign metastasizing leiomyoma, and diffuse leiomyomatosis. Their clinicopathologic features, differential diagnoses, and management options based on findings in the previously reported cases will also be reviewed. Copyright © 2010 by Lippincott Williams & Wilkins.link_to_subscribed_fulltex