Epithelial-Mesenchymal Transition Markers ß-catenin, Snail, and E-Cadherin do not Predict Disease Free Survival in Prostate Adenocarcinoma: a Prospective Study.

Current methods for diagnosis and staging of prostate adenocarcinoma are not sensitive enough to distinguish between patients with indolent disease and those that should receive radical treatment. Epithelial-mesenchymal transition (EMT) is a well-characterized process involved in tumor invasion and metastasis. The aim of this study is to analyze the expression of ß-catenin, Snail, and E-cadherin in prostate cancer patients with prospective evaluation of their value in predicting disease-free survival (DFS). One-hundred-and-three consecutive prostate carcinoma patients who underwent radical prostatectomy and 35 patients with benign prostate hyperplasia (BPH) were enrolled. Age, initial PSA level, tumor size and clinical stage were documented for adenocarcinoma patients and they were enrolled in active surveillance with serum PSA levels. Recurrence was defined as PSA level of ≥ 0.2 ng/ml on at least 2 occasions over a 2-month period. Immunohistochemical staining intensity was scored as negative, weakly positive, moderately positive, and strongly positive. For Snail and ß-catenin immunoreaction, the tumors were considered nuclear positive when more than 5 % of the nuclei of tumor cells were positively stained. Patients with prostate cancer had weaker ß-catenin (p < 0.0001), Snail (p = 0.006), and E-cadherin (p = 0.02) staining when compared to BPH patients and the frequency of nuclear positivity for ß-catenin and Snail were higher in adenocarcinoma group (p < 0.0001). Increased expression and nuclear positivity of ß-catenin were associated with advanced stage (p = 0.012 and p = 0.003) and higher tumor volume (p = 0.013 and p = 0.002). Additionally, patients with increased Snail expression had higher Gleason scores and tumor volume at presentation (p = 0.008 and p = 0.004). However, there were no significant DFS differences in adenocarcinoma patients who did and did not have ß-catenin, Snail, and E-cadherin expression as assessed with log-rank test. Expressions of ß-catenin, Snail, and E-cadherin were significantly lower in prostate cancer patients compared to BPH patients and both ß-catenin and Snail had nuclear staining pattern in patients with adenocarcinoma. However, none of these markers predicted DFS in 36-month follow up of our cohort.

Skin cancer in immunosuppressed transplant patients: Vigilance matters.

Liver transplantation (LT) is a widely-accepted, definitive therapy of irreversible liver diseases including hepatitis C, alcoholic liver disease and metabolic liver disease. After transplantation, patients generally use a variety of immunosuppressive medications for the rest of their lives to prevent rejection of transplanted liver. Mortality after LT is mainly caused by recurrence of alcoholic hepatitis which is mostly seen in the patients who resume heavy drinking. On the other hand, de-novo malignancies after LT are not seldom. Skin cancers make up 13.5% of the de-novo malignancies seen in these patients. Malignancies tend to affect survival earlier in the course with a 53% risk of death at 5 years after diagnosis. We aimed to report a case who underwent LT secondary to alcoholic liver disease and developed squamous cell carcinoma of the skin eighteen years after transplantation. In summary, transplant recipients are recommended to be educated on self examination for skin cancer; health care providers should be further suspicious during routine dermatological examinations of the transplant patients and biopsies of possible lesions for skin cancer is warranted even many years after transplantation.

Suicidal ideation among patients with Behçet's syndrome.

OBJECTIVES: To evaluate the frequency of suicidal ideation among Behçet's syndrome (BS) patients compared to healthy and diseased controls and to delineate possible factors predicting an increase in suicidal ideation. METHODS: We included consecutive BS patients attending our outpatient clinic, patients with ankylosing spondylitis (AS) and healthy hospital staff as controls. Suicidal ideation was assessed by a standard questionnaire. Linear regression was used to identify the factors associated with suicidal ideation, such as demographic and clinical features, drugs, disease activity assessed using the Behçet's disease current activity form (BDCAF) for BS patients and BASDAI for AS patients, Behçet's disease quality of life (BDQoL) and Beck depression inventory (BDI) score. RESULTS: We surveyed 303 BS patients, 52 AS patients and 106 healthy controls. Suicidal thoughts, as reflected by a positive response to the first three items of the questionnaire, were higher among BS patients with major organ involvement (42%) than those with mucocutaneous involvement (35%) and the control groups. There were significantly more BS patients with active major organ involvement who had thought to terminate their lives without plans within the last year (25.5%) compared to those with active mucocutaneous involvement (8.7%) and active AS patients (10%) (p=0.012). Patient-reported joint pain (ß=-0.155, p=0.046), BDQoL (ß=0.176, p=0.032), and BDI (ß=0.017, p<0.0001) scores, suicidal thoughts before the onset of BS (ß=-0.124, p=0.043), neurologic involvement (ß=0.119, p=0.047) and past prednisone use (ß=0.212, p=0.005) were independent predictors of suicidal thoughts. CONCLUSIONS: BS patients with major organ involvement have increased thoughts of suicide during the active stages of their disease. A number of risk factors could help physicians to identify patients with increased suicidal thoughts.

Currently Used Biologic Agents in the Management of Behcet's Syndrome.

Behcet's s yndrome (BS) is a multisystem vasculitis with frequent mucocutaneous, joint, eye and visceral organ involvement. From early 2000s, biologic drugs have been increasingly used in the management of BS, enabling rapid and complete remission in most cases with critical organ involvement. Despite the current experience with steroids and traditional immunosuppressives, biologics are exceptionally promising for treatment of resistant cases. Among the biologics used in BS, TNF-alpha antagonists are the oldest and their efficacy has been proven in recalcitrant ocular, vascular, gastrointestinal and neurologic involvements. These drugs have significantly reduced morbidity and mortality in BS and they have an acceptable safety profile. Tocilizumab, an IL6 receptor antibody, has been shown to be effective in BS patients with neurologic involvement and amyloidosis, and IL1ß antagonists such as anakinra, canakinumab, gevokizumab were effective in the management of ocular involvement. Studies investigating the efficacy of daclizumab, IL2 receptor antibody, and secukinumab, IL17 monoclonal antibody, in the management of BS with eye involvement failed to demonstrate significant clinical improvement and both studies were halted. A monoclonal vascular endothelial growth factor antagonist, bevacizumab, was shown to be effective in BS-related macular edema. Alemtuzumab and ustekinumab are among other biologics which were effective in controlling disease symptoms. In this review, we discuss the efficacy and safety of various recently developed biologic agents targeting different pathways involved in the pathogenesis of BS.

A 17-year experience with ALL-BFM protocol in acute lymphoblastic leukemia: prognostic predictors and interruptions during protocol.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and despite the intense combination chemotherapy, cure rates are less than 90%. Several prognostic parameters, including nonneoplastic hematologic cell counts during induction phase, are suggested to predict outcome in ALL. We analyzed 242 ALL patients treated in our center to investigate individual prognostic parameters and the impact of delays on disease outcome. Age at diagnosis, risk groups, extramedullary involvement, t(9;22), prednisone response, bone marrow response at days 15 and 33, day 15 platelet count, day 33 lymphocyte, monocyte, and platelet counts, treatment delay, sepsis, and omission of day 64 cyclophosphamide were valuable predictors of survival in univariate analysis. However only the age, CNS involvement, omission of cyclophosphamide, and total delay during treatment were associated with survival in multivariate analysis. Omission of second cyclophosphamide dose had no impact on survival of standard risk group patients, but adversely affected the long term survival of medium risk group (MRG) patients. The second dose might be given with the first dose on day 36 to MRG patients to prevent delays. Day 15 and 33 platelet counts are promising predictors of survival in low income countries where assessment of minimal residual disease is difficult, but this data needs further consolidation.

No appreciable decrease in fertility in Behçet's syndrome.

OBJECTIVES: Behçet's syndrome (BS) follows an active course during the childbearing years in both men and women. We formally surveyed the infertility rate and the effect of drugs and types of organ involvement on fertility in BS. METHODS: We compared fertility among BS patients with and without major organ involvement with those with FMF, AS and healthy controls. A structured interview was performed and the medical records of the patients were reviewed to confirm the sites of involvement and drugs they used during their entire follow-up. RESULTS: The number of female patients who were not able to ever conceive, who were not able to conceive before or after disease onset or who were able to conceive late or only with assisted reproductive technology was not increased among the BS group. The same was true for the male patients to successfully achieve a conception and/or father a child. The average number of children, miscarriages, terminations and ectopic pregnancies were similar among the groups. Infertility was more common in BS patients with major organ involvement who used cyclophosphamide (CYC) compared with those who did not (P = 0.009). CONCLUSION: Infertility is not appreciably increased among BS patients attending a dedicated outpatient clinic. Major organ involvement does not increase the risk of infertility and CYC is the only drug that seems to compromise fertility in BS.

Dendritic cell sarcoma: a pooled analysis including 462 cases with presentation of our case series.

Dendritic cell tumors are extremely rare and current knowledge on these tumors is limited. The characteristics of three dendritic cell sarcoma subtypes and their optimal treatment approaches are not fully clarified. We aimed to make a systematic review of the literature and enrich the current data with five new cases. Pooled analysis of 462 reported cases revealed that the tumor had no age, gender or racial predilection. Our analysis suggests that the young age, advanced stage, intraabdominal involvement and unfavorable histological features (i.e. large tumor size, absence of lymphoplasmacytic infiltration, coagulative necrosis, high mitotic count) may predict poor prognosis. Subtypes of this tumor have different clinical behaviors with interdigitating dendritic cell sarcoma being the most aggressive form. In general, surgery is the most effective treatment modality and adjuvant radiotherapy has no significant effect on overall survival of patients. The role of chemotherapy for the management of advanced disease is controversial.

Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.

UNLABELLED: Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. OBJECTIVES: To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. METHODS: Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. RESULTS: Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. CONCLUSION: In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors.

Expression of MMP-1, MMP-9 and TIMP-2 in prostate carcinoma and their influence on prognosis and survival.

PURPOSE: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) participate in tumorigenesis, and their association with disease outcome is highly controversial. The present study investigates the influence of MMP-1, MMP-9 and TIMP-2 on different clinicopathologic variables and disease-free survival (DFS) of patients with prostate carcinoma. METHODS: Hundred and forty-five cases are included in the study, and levels of MMP/TIMP expressions are assessed in three tissue compartments (i.e., tumor, stroma and normal glands) with immunohistochemistry. RESULTS: Matrix metalloproteinase-1 expression in tumor cells was associated with lower Gleason scores, pretreatment prostate-specific antigen levels and lower incidence of vascular, perineural and extracapsular invasions. Moreover, MMP-9 positivity and TIMP-2 expression in normal glands were correlated with lower Gleason patterns and early stage at presentation. Expression of MMP in tumor cells and the presence of TIMP-2 in normal glands were associated with better DFS. CONCLUSION: Variability of MMP/TIMP expressions from case to case makes it difficult to evaluate their impact on clinical outcome. However, these proteins might be new and promising targets for prostate cancer therapy in the future.

Novel use of propranolol for management of pain in children with vertebral hemangioma: report of two cases.

INTRODUCTION: Vertebral hemangioma (VH) is an exceedingly rare neoplasm in pediatric population with less than 10 cases reported in the literature. It is usually asymptomatic in adults and diagnosed incidentally at radiographic investigations of other medical conditions. In this report, we describe two children who presented to our institution with severe back pain and were diagnosed with VH. CASE REPORTS: Case 1 was an 8-year-old male with a pain score of 10 out of 10 at presentation. Clinical investigations eliminated the possibility of a neoplasm or infectious process and MRI findings were highly suggestive of an aggressive vertebral hemangioma. Case 2 was a 17-year-old female who presented with back pain radiating to shoulders. Her pain score was 4 out of 10 and she was diagnosed with vertebral hemangioma due to the specific findings on MRI studies. DISCUSSION: Both patients received propranolol with a dose of 20 and 40 mg per day, respectively. They were free of pain at 2 months follow-up. There are different invasive treatment modalities for the management of VH, including vertebroplasty, kyphoplasty, radiotherapy, alcohol injection, embolization, and surgery. These methods have been used in adult patients for several years, but each of them has potential risks which make these options unsuitable for children. CONCLUSION: Propranolol is a beta blocker which is safely used in the management of infantile hemangiomas. This is the first report demonstrating its efficacy in symptomatic treatment of childhood VH. The lesions did not show any regression, but the pain relief obtained was very significant under propranolol therapy.