Cholangiocarcinoma in Primary Sclerosing Cholangitis

Introduction

Cholangiocarcinoma (CCA) is an aggressive and nearly always fatal tumor of the biliary tract.

Purpose

This review explores risk factors, epidemiology, current diagnostic approaches, and treatment of CCA arising in patients with primary sclerosing cholangitis (PSC).

Methods

We review latest recommendations about screening strategies to enable the early detection of CCA in PSC, using CA 19-9 and ultrasound imaging, as well as fluorescent in situ hybridization techniques to enhance the accuracy of biliary cytology. We also review the emerging role of liver transplantation.     

Cutaneous sebaceous neoplasms as markers of Muir-Torre syndrome: a diagnostic algorithm

Sebaceous gland neoplasms such as adenoma, epithelioma, and carcinoma are uncommon cutaneous tumors. Although sporadic, their occurrence is clinically significant because of their association with Muir‐Torre syndrome (MTS). MTS is a rare autosomal dominant genodermatosis characterized by the occurrence of sebaceous gland neoplasms and/or keratoacanthomas associated with visceral malignancies that include gastrointestinal and genitourinary cancers. MTS is usually the result of germline mutation in one or more of the DNA mismatch repair (MMR) genes. MMR genes commonly implicated include MSH‐2 and MLH‐1 and, more recently, MSH‐6. Recent evidence suggests that immunohistochemistry is very sensitive and effective in detecting these defects in cutaneous tumors in MTS. In addition, the genetic instability of cutaneous and visceral tumors in MTS caused by the defects in MMR genes can also be detected, using polymerase chain reaction (PCR)‐based techniques, for microsatellite instability (MSI). Given that some sebaceous neoplasms represent cutaneous markers of MTS, what should we as dermatopathologists be advocating? Should we be looking for absence/loss of MMRs in all sebaceous neoplasms? When should we recommend assaying for MSI? This review attempts to address all of these issues with a view to streamlining the work‐up of a patient presenting for the first time with a sebaceous neoplasm and no prior personal or family history of internal malignancies.     

Prognostic factors of survival time after hematopoietic stem cell transplant in acute lymphoblastic leukemia patients: Cox proportional hazard versus accelerated failure time models

Background

The aim of this study is to evaluate the prognostic factors of overall survival (OS) after haematopoietic stem cell transplant (HSCT) in acute lymphoblastic leukaemia (ALL) patients using accelerated failure time (AFT), Cox proportional hazard (PH), and Cox time-varying coefficient models.

Methods

206 patients were enrolled after HSCH in Shariati Hospital between 1993 and 2007. There was evidence of marked departures from the proportional hazards assumption with two prognostic factors, relapse and chronic graft-versus-host disease (cGVHD) (P < .001). Performance among AFT and Cox''s models was assessed using explained variation and goodness of fit methods. Discrimination among the exponential, Weibull, generalized gamma (GG), log-logistic, and lognormal distributions was done using maximum likelihood and Akaike information criteria.

Results

The 5-year OS was 52% (95%CI: 47.3–56.7). Peak mortality hazard occurred at months 6–7 after HSCT followed by a decreasing trend. In univariate analysis, the data was better fitted by GG distribution than by other distributions. Univariate analysis using GG distribution showed a positive association between OS with acute graft-versus-host disease (aGVHD) (P = .021), no relapse (P < .001), cGVHD (P < .001), neutrophil recovery (P < .001) and platelet recovery (P < .001). Based on Cox PH models; however cGVHD and relapse were the predictive factors of OS (P < .001). Multivariate analysis indicated that, OS is related to relapse (P < .001) and platelet recovery (P = .037), where predictive power of Weibull AFT models was superior to Cox PH model and Cox with time-varying coefficient (R² = 0.46 for AFT, R² = .21 for Cox PH and R² = .34 for Cox time-varying coefficient). Cox-Snell residual shows Weibull AFT fitted to data better than other distributions in multivariate analysis.

Conclusion

We concluded that AFT distributions can be a useful tool for recognizing prognostic factors of OS in acute lymphoblastic leukemia patients.     

A Flowcytometry Study of CD55 and CD59 Expression on Erythrocytes in Rheumatoid Arthritis Patients

Background: Inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect the unnecessary activation of complement components.   Objective: To investigate the expression of CD55 and CD 59 complement regulatory proteins in RA patients. Subjects and Methods: Fifty proved rheumatoid arthritis patients participated in this study and their blood were collected for investigations. CD55 and CD59 molecules expression on the erythrocytes was assayed using primary monoclonal antibody and secondary FITC conjugated Ab, then the prepared samples were run with a FACSCalibur flowcytometer (Becton-Dickinson) and the obtained data was analyzed using a Cell Quest software package. To evaluate the complement function, CH50 was performed using patient sera. All experiments were done with a matched healthy volunteer group.   Results: The mean fluorescence intensity for CD55 was 27.6 ± 13.4 arbitrary unit for patients and 68.5 ± 10.5 for healthy group. CD59 mean fluorescence intensity was 314 ± 83 in patient group and 508 ± 56 in healthy volunteers. In addition, there was a significant difference between CH50 in patients (54.5 ± 15.5) and in healthy group (110 ± 20). A significant correlation between CD55 and CD59 expansion on the patient erythrocytes was found (P = 0.00, r = 0.576). No association was found between CD59, or CD55 with CH50 (P > 0.05).   Conclusion: The expression of CD55 and CD59 is down-regulated on erythrocytes of patients with RA. Change in expression of regulatory complement components in RA may be a useful key for the assessment of disease progression or in patients' follow-up.