Hepatitis E Virus in the United States and Canada: Is It Time to Consider Blood Donation Screening?

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.

Severe acute haemolytic transfusion reaction secondary to a plasma incompatible group B platelet transfusion.

OBJECTIVES: To report a rare case of acute hemolytic transfusion reaction (AHTR) following an ABO plasma incompatible group B platelet transfusion. BACKGROUND: AHTR is an uncommon, but potentially fatal event. Most reported cases of platelet transfusions associated with AHTR involve group O donors. CASE REPORT: A 34-year-old man, recipient of a group AB haploidentical haematopoietic stem cell transplantation (HSCT), had received re-induction chemotherapy for leukaemia relapse. A group B whole blood-derived buffy coat platelet pool was transfused. He developed rigours/fever, profound hemolytic anaemia, and hemodynamic instability. Serological investigations revealed AHTR from passive transfer of high titre anti-A (256 for IgM and 8192 for IgG). DISCUSSION: This case highlights the potential risks associated with ABO-mismatched transfusions, and the complexity associated with transfusing HSCT recipients and red cell transfusion recipients with dual populations of circulating red cells. The literature on minor ABO plasma incompatible transfusions, challenges in establishing local policies to limit the risks of AHTR and risk mitigation strategies are discussed. CONCLUSION: Clinicians must maintain a high level of suspicion for AHTR after ABO plasma incompatible platelet transfusions. Patients must be aware of the risks of AHTR, and early recognition and diagnosis of this complication may be lifesaving.

Severe Cystic Echinococcosis-Associated Immune Thrombocytopenic Purpura: A Case Report.

We present a case of immune thrombocytopenic purpura (ITP), which leads to the diagnosis of severe cystic echinococcosis. Our patient presented with platelets of 5 × 109/L, and investigations uncovered multiple large echinococcal hepatic cysts, the largest of which measured 19.4 × 15 × 12 cm, and peritoneal implants. While initially refractory to prednisone and immunoglobulins, the ITP responded to dexamethasone. The echinococcosis was treated with albendazole followed by surgical resection of all lesions. Our patient's disease course has evolved favorable since his initial treatment with an isolated episode of recurrent thrombocytopenia 2 years later, and has remained in remission for the past 2 years. While a causal association between echinococcosis and ITP cannot be confirmed, this case is a reminder of the importance of remaining inquisitive for atypical potential triggers of ITP. We also present a review of the limited literature on the association of parasitic infections and ITP.

Molecular Pathogenesis of Hodgkin Lymphoma: Past, Present, Future.

Our understanding of the tumorigenesis of classical Hodgkin lymphoma (cHL) and the formation of Reed-Sternberg cells (RS-cells) has evolved drastically in the last decades. More recently, a better characterization of the signaling pathways and the cellular interactions at play have paved the way for new targeted therapy in the hopes of improving outcomes. However, important gaps in knowledge remain that may hold the key for significant changes of paradigm in this lymphoma. Here, we discuss the past, present, and future of cHL, and review in detail the more recent discoveries pertaining to genetic instability, anti-apoptotic signaling pathways, the tumoral microenvironment, and host-immune system evasion in cHL.

Bone Marrow Immunohistochemistry and Flow Cytometry in the Diagnosis of Malignant Hematologic Diseases With Emphasis on Lymphomas: A Comparative Retrospective Study.

We aim to evaluate the degree of agreement between immunohistochemistry (IHC) and flow cytometry (FC) in the diagnosis of malignant hematologic diseases, mainly lymphomas. A total of 260 bone marrow biopsies, 255 bone marrow aspirates, and 5 other suspensions of 260 patients used for diagnosis of a hematologic malignancy between 2009 and 2012 with both, IHC and FC, were retrospectively analyzed. Overall there is a substantial degree of agreement (κ=0.69) between IHC and FC. Chronic lymphocytic leukemia/small lymphocytic lymphoma, mature T-cell neoplasms, acute leukemias, and myelodysplastic syndromes had the highest concurrence rates (>80%). In nonconcordant cases, an IHC provided diagnosis in 25.4%, and an FC in 4.6%. Lymphomas were diagnosed by an IHC only in 51% of the cases. Both methods have good concurrence rates and are complementary. An IHC has the advantage of combining markers, morphology, and tissue immunoarchitecture, which is beneficial in the diagnosis of lymphomas. An FC is required in leukemias as it is faster and plays an important role in minimal residual disease.

A Novel Human ß-Globin Gene Variant [Hb London-Ontario, HBB: c.332T>G] is Associated with Transfusion-Dependent Anemia in a Patient with a Hemoglobin Electrophoresis Pattern Consistent with ß-Thalassemia Trait.

We present the case of a novel ß-globin gene variant associated with early-onset transfusion-dependent anemia compatible with a ß-thalassemia major (ß-TM) phenotype in a patient of British descent. As a child, our patient developed chronic symptomatic anemia with hemoglobin (Hb) nadirs of 3.0 g/dL. She started receiving occasional transfusions by the age of 13 years and became transfusion-dependent by the age of 32 years. Work-up performed at our center showed a Hb electrophoresis compatible with ß-thalassemia (ß-thal) trait. Polymerase chain reaction (PCR) of the ß-globin gene detected a novel mutation situated at codon 110 (CTG). This missense mutation led to a substitution of the thymine nucleotide (nt) base for guanine (CGG) at position 332 (HBB: c.332T>G). We have named this new mutation Hb London-Ontario. The majority of previously described dominant allelic mutations of the ß-globin gene led to a ß-thal intermedia (ß-TI) phenotype. The heterozygous mutation which was detected in our patients is unique at it leads to a more severe ß-TM phenotype. We suspect this is a de novo mutation of which the mother of our patient, who was reported to have a form of thalassemia, was the proband.

Low endoscopy bleeding risk in patients with congenital bleeding disorders.

INTRODUCTION: Haemophilia A and haemophilia B, von Willebrand disease (VWD), factor VII deficiency and factor XI deficiency are congenital bleeding disorders predisposing to bleeding during invasive procedures. The ageing population of people with congenital bleeding disorders will likely increasingly require gastrointestinal endoscopy. The bleeding risk postgastrointestinal endoscopy and optimal prophylactic treatment regimens are not well described. METHODS: We performed a retrospective chart review at the McGill University Health Centre. Adult patients with haemophilia A or B, VWD, FVII deficiency and FXI deficiency who underwent gastrointestinal endoscopic procedures were included. Bleeding prophylaxis included combinations of plasma-derived factor (VWD) or recombinant factor (haemophilia A and haemophilia B), desmopressin and/or tranexamic acid. Our primary outcome was the 72-hour postendoscopy bleeding rate. RESULTS: One hundred and four endoscopies were performed in 48 patients. Haemophilia A (45.3% of endoscopies) was the most common bleeding disorder, followed by VWD (38.5%), FXI deficiency (8.7%), haemophilia B (4.8%) and FVII deficiency (2.9%). All patients were reviewed by the Haemophilia Treatment Center with peri-procedure treatment protocols put in place as required. The overall 72-hour bleeding rate was 0.96%, confidence interval (CI) 95% (0.17%-5.25%). The colonoscopic postpolypectomy bleeding rate was 1/21 (4.8%, CI 95% (0.9%-22.7%)) in comparison with the general population rate of 0.3%-10% for high-risk endoscopy (including colonoscopic polypectomy). CONCLUSION: To the best of our knowledge, this is the largest study describing patients with inherited bleeding disorders undergoing gastrointestinal endoscopy. The bleeding risk is not significantly higher to the general population when haemostatically managed by a team experienced in bleeding disorders.

IκB-Kinase-epsilon (IKKε) over-expression promotes the growth of prostate cancer through the C/EBP-ß dependent activation of IL-6 gene expression.

The inflammatory cytokine IL-6 has been shown to induce the nuclear translocation of androgen receptors in prostate cancer cells and to activate the androgen receptors in a ligand-independent manner, suggesting it may contribute to the development of a castrate-resistant phenotype. Elevated IL-6 serum levels have also been associated with metastasis-related morbidity in prostate cancer patients. We have previously established that over-expression of I-kappa-B-kinase-epsilon (IKKε also named IKKi or IκBKε) in hormone-sensitive prostate cancer cell lines induces IL-6 secretion. We have also reported that prostate cancer cell lines lacking androgen receptor expression exhibit high constitutive IKKε expression and IL-6 secretion. In the present study, we validated the impact of IKKε depletion on the in vitro proliferation of castrate-resistant prostate cancer cells, and characterized how IKKε depletion affects tumor growth and IL-6 tumor secretion in vivo through a mouse xenograft-based approach. We observed a significant growth delay in IKKε-silenced PC-3 cells injected in SCID mice fed with a doxycycline-supplemented diet in comparison with mice fed with a normal diet. We also found a decrease in IL-6 secretion levels that strongly correlated with tumor growth inhibition. Finally, using constructs with various IL-6-mutated promoters, we demonstrated that IKKε over-expression induces a NF-κB-independent stimulation of the IL-6 gene promoter through the activation and nuclear accumulation of the transcription factor C/EBP-ß. Our study demonstrates the pro-proliferative role of the oncogene IKKε in castrate-resistant prostate cancer cell lines, involving the phosphorylation and nuclear translocation of C/EBP-ß that initiates IL-6 gene expression.

Erectile function recovery after robotic-assisted radical prostatectomy (RARP): long term exhaustive analysis across all preoperative potency categories.

INTRODUCTION: To evaluate erectile function recovery following robotic-assisted radical prostatectomy (RARP) according to preoperative sexual health inventory for men (SHIM) score stratification. MATERIALS AND METHODS: We prospectively collected data on 250 consecutive patients who underwent RARP by a single surgeon between October 2006 and October 2012. Thirty-six patients were excluded because of lack of preoperative SHIM score. All patients had a minimum follow up of 2 years. Patients were divided into four groups according to their preoperative SHIM score: group 1 with normal potency (SHIM 22-25), group 2 with mild ED (SHIM 17-21), group 3 with mild-moderate ED (SHIM 12-16) and group 4 with moderate-severe ED (SHIM 1-11). Patients were followed at 3, 6, 9, 12, 18, 24 months intervals and twice yearly thereafter. SHIM questionnaire and erection hardness scale (EHS) score were collected at each visit. Potency was defined as successful penetration during intercourse (EHS score 3-4) with or without phosphodiesterase type 5-inhibitor (PDE5-I). RESULTS: After exclusion, 214 patients were evaluated. The number of patients in group 1, 2, 3 and 4 were 95, 59, 26 and 34, respectively. At 3, 6, 9, 12, 18, 24 months, SHIM scores and potency rates were statistically different between groups 1 versus 2 versus 3 versus 4 (p < 0.01, at each time point). Patients in each group 1, 2 and 3 showed a statistically significant improvement in potency rates and SHIM scores at consecutive follow up visits up to 24 months (p < 0.01, for each potency group). Potency rates at 24 months for groups 1 to 4 were 83.3%, 54.5%, 50.0%, and 20.7%, respectively (p < 0.001). CONCLUSION: For proper patient counseling and better prediction of erectile function recovery after RARP, it is important to stratify patients according to preoperative SHIM scores. Setting realistic expectations may increase patient satisfaction.

Microcirculatory response during on-pump versus off-pump coronary artery bypass graft surgery.

OBJECTIVES: The use of cardiopulmonary bypass (CPB) during coronary artery bypass graft surgery (CABG) is associated with a systemic inflammatory response, resulting in altered microcirculation. The aim of this study was to evaluate whether beating heart surgery can preserve the microcirculation. METHODS: Sublingual microcirculation was characterized by a Sidestream Darkfield Imaging Microscope during off-pump (OPCABG) and on-pump (ONCABG) surgery. Microcirculatory parameters were evaluated during eight precise perioperative time points. RESULTS: The quality of the microcirculation decreased during early ONCABG. OPCABG resulted in a significantly better microcirculation compared to ONCABG for three of six parameters during surgery. However, by the end of surgery and postoperatively, the microcirculatory parameters were no different between the groups. CONCLUSIONS: While the results do not show a marked preservation of the microcirculation during and after OPCABG compared to ONCABG, they coincide with the body temperature fluctuations of each group during and after surgery. Our work suggests that active warming could impact the microcirculation parameters.

Prevalence and risk factors of contralateral extraprostatic extension in men undergoing radical prostatectomy for unilateral disease at biopsy: A global multi-institutional experience.

INTRODUCTION: We assessed the incidence of contralateral prostate cancer (cPCa), contralateral EPE (cEPE) and contralateral positive surgical margins (cPSM) in patients diagnosed preoperatively with unilateral prostate cancer and evaluated risk factors predictive of contralateral disease extension. METHODS: The occurrence of cPCa, cEPE and cPSM and the side-specific nerve-sparing technique performed were collected postoperatively from 327 men diagnosed with unilateral prostate cancer at biopsy. Parameters, such as the localization, proportion, and percentage of cancer in positive cores, were prospectively collected. RESULTS: Overall, 50.5% of patients had bilateral disease, and were at higher risk when associated with a positive biopsy core at the apex (p = 0.016). The overall incidence of ipsilateral EPE and cEPE were 21.4% and 3.4%, respectively (p < 0.001). Compared to cPCa, ipsilateral disease was at an almost 4-fold higher risk of extending out of the prostate (p < 0.001). None of the criteria tested were identified as useful predictors for cEPE. The low incidence of cEPE in our cohort could limit our ability to detect significance. The overall incidence of ipsilateral PSM and cPSM were 15.3% and 5.8%, respectively (p < 0.001). More aggressive nerve-sparing was not associated with a higher incidence of PSM. Prostate sides selected for more aggressive nerve-sparing were associated with younger patients (p < 0.001), a smaller prostate (p = 0.006), and a lower percentage of cancer in biopsy material (p = 0.008). CONCLUSION: Although the risk of cPCa is high in patients diagnosed with unilateral prostate cancer at biopsy, the risk of cEPE and cPSM is low, yet not insignificant. Contralateral aggressive nerve-sparing should be used with caution and should not compromise oncological outcome.

Factors predicting prolonged operative time for individual surgical steps of robot-assisted radical prostatectomy (RARP): A single surgeon's experience.

INTRODUCTION: We evaluated the average time required to complete individual steps of robotic-assisted radical prostatectomy (RARP) by an expert RARP surgeon. The intent is to help establish a time-based benchmark to aim for during apprenticeship. In addition, we aimed to evaluate preoperative patient factors, which could prolong the operative time of these individual steps. METHODS: We retrospectively identified 247 patients who underwent RARP, performed by an experienced robotic surgeon at our institution. Baseline patient characteristics and the duration of each step were recorded. Multivariate analysis was performed to predict factors of prolonged individual steps. RESULTS: In multivariable analysis, obesity was a significant predictor of prolonged operative time of: docking (odds ratio [OR] 1.96), urethral division (OR 3.13), and vesico-urethral anastomosis (VUA) (OR 2.63). Prostate volume was also a significant predictor of longer operative time in dorsal vein complex ligation (OR 1.02), bladder neck division (OR 1.03), pedicle control (OR 1.04), urethral division (OR 1.02), and VUA (OR 1.03). A prolonged bladder neck division was predicted by the presence of a median lobe (OR 5.03). Only obesity (OR 2.56) and prostate volume (OR 1.04) were predictors of a longer overall operative time. CONCLUSIONS: Obesity and prostate volume are powerful predictors of longer overall operative time. Furthermore, both can predict prolonged time of several individual RARP steps. The presence of a median lobe is a strong predictor of a longer bladder neck division. These factors should be taken into consideration during RARP training.

Management of bone metastases in prostate cancer: a review.

PURPOSE OF REVIEW: Bone metastases in the advanced stages of prostate cancer have a detrimental effect on the quality of life, resulting in skeletal-related events and pain and place a significant burden on healthcare resources. Improvements in prostate cancer treatment have led to a longer survival of patients. Therefore, quality of life is of growing interest and importance. Successful management and prevention of the complications of bone metastasis in those patients remains, however, clinically challenging. RECENT FINDINGS: Recently, radium-223 was approved as a treatment for bone metastasis in patients with prostate cancer, joining zoledronic acid, denosumab and other radiopharmaceuticals in the clinical armamentarium. Radium-223 has shown to improve overall survival in patients with bone metastasis. SUMMARY: This review focuses on the recent landmark studies on zoledronic acid, denosumab and radium-223 for patients with metastatic prostate cancer and gives a comprehensive overview of their mechanism of action, efficacy, dosage and safety profile.

Uroflow Stop Test and Potency Recovery: A Surrogate for Pelvic Floor Integrity Post Robotic-Assisted Radical Prostatectomy?

OBJECTIVE: To study the relation between uroflow Stop Test and early recovery of potency following robot-assisted radical prostatectomy (RARP). We recently showed that the ability to completely stop urine flow during voiding, measured objectively by uroflowmetry at the time of catheter removal (uroflow Stop Test) can predict early urinary continence recovery following RARP. MATERIALS AND METHODS: In this prospective observational cohort, data were collected on 108 patients operated by a single surgeon (AEH). Eighty patients had a positive uroflow Stop Test (group one) and 28 had a negative Stop Test (group two). Patients were followed for a minimum of 2 years. Covariates included age, body mass index, international prostate symptom score and sexual health inventory for men scores, prostate-specific antigen, tumor stage, prostate volume, nerve sparing status, and estimated blood loss. RESULTS: Preoperative characteristics were comparable between both groups except nerve sparing and prostate-specific antigen which were statistically higher in group one (P <.05). Early 3- and 6-months recovery of erectile function was significantly higher in group one. Potency rates in group one and two at 1, 3, 6, 9, 12, 18, and 24 months were 25% vs 14.3% (P = .241), 54.5% vs 18.5% (P = .001), 55.4% vs 18.5% (P = .001), 56.4% vs 36% (P = .084), 66.6% vs 50% (P = .141), 65.5% vs 56% (P = .404) and 73.2% vs 57.7% (P = .160) respectively. Uroflow Stop Test was independent predictor of early potency recovery on multivariate regression analysis at 6 months [odds ratio 6.042 (confidence interval 95% 1.496-24.413) P = .012]. CONCLUSION: Uroflow Stop Test is simple and can help predict early potency recovery following RARP.

Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review.

Androgen-deprivation therapy (ADT) has become a standard of care in the management of advanced prostate cancer or as an adjunct therapy. However, ADT is associated with a well-known deleterious effect on bone health, resulting in a decrease in bone-mass density (BMD) and increased risk for fracture. With the longer life expectancy of prostate cancer patients, improvement of the quality of life has become increasingly important. Therefore, adequate screening, prevention and treatment of BMD loss is paramount. Zoledronic acid and denosumab have shown promising results in recent studies, which has led to the Food and Drug Administration approval of these treatment options in various settings throughout the course of the disease, including the prevention of ADT-associated bone loss. This review focuses on the various parameters that impact BMD loss in men initiating ADT, on the specific effect of ADT on bone health and on various lifestyle modifications and treatment options such as bisphosphonates, osteoclast-targeted therapy and selective estrogen-receptor modulators that have shown promising results in recent studies.

Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on Safety and Outcomes.

PURPOSE: We evaluated photoselective vaporization of the prostate using the GreenLight™ XPS™ 180 W system for benign prostatic hyperplasia treatment in a large multi-institutional cohort at 2 years. We particularly examined safety, outcomes and the re-treatment rate in larger prostates, defined as a prostate volume of 80 cc or greater, to assess the potential of photoselective vaporization of the prostate as a size independent procedure. MATERIALS AND METHODS: A total of 1,196 patients were treated at 6 international centers in Canada, the United States, France and England. All parameters were collected retrospectively, including complications, I-PSS, maximum urinary flow rate, post-void residual urine, prostate volume, prostate specific antigen and the endoscopic re-intervention rate. Subgroup stratified comparative analysis was performed according to preoperative prostate volume less than 80 vs 80 cc or greater on transrectal ultrasound. RESULTS: Median prostate size was 50 cc in 387 patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc or greater, respectively. The rate of conversion to transurethral prostate resection was significantly higher in the 80 cc or greater group than in the less than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum urinary flow rate and post-void residual urine were significantly improved compared to baseline at 6, 12 and 24 months of followup without significant differences between the prostate size groups. The re-treatment rate at 2 years reported in 5 of 411 patients was associated with the delivery of decreased energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. CONCLUSIONS: Photoselective vaporization of the prostate using the XPS 180 W system is safe and efficacious, providing durable improvement in functional outcomes at 2 years independent of prostate size when treated with sufficient energy.