Prostate cancer risk after anti-androgen treatment for priapism

Background

Patients with recurrent ischemic priapism have historically been treated with anti-androgen therapy due to the limited available evidence for more targeted therapies to treat the underlying pathophysiologic mechanisms of this condition. We report a case in which anti-androgen therapy caused significant adverse side effects and likely masked this patient’s elevated prostate-specific antigen (PSA) levels, which adversely impacted the timely diagnosis and treatment of his prostate cancer.

Case report

A 69-year-old man treated with anti-androgens for priapism initially developed unwanted anti-androgenic side effects such as gynecomastia, erectile dysfunction, and decreased libido. After decreasing his anti-androgen dosage and starting a specified regimen of phosphodiesterase type 5 inhibitor therapy, his serum PSA levels were found to be elevated. He was subsequently diagnosed with adenocarcinoma of the prostate and underwent a radical prostatectomy with the pathologic finding of high-grade, locally progressive disease.

Conclusion

Anti-androgen therapy carries significant complication risks, including the potential to alter the diagnosis and treatment of prostate cancer. Clinicians administering this therapy for priapism management should be aware of these possible risks.     

Combining routine morphology,p16INK4a immunohistochemistry,and in situ hybridization for the detection of human papillomavirus infection in penile carcinomas: A tissue microarray study using classifier performance analyses

ObjectivesInfection by high-risk human papillomavirus (HR-HPV) plays an important role in the pathogenesis of penile cancer in approximately 50% of the patients. The gold standard for human papillomavirus (HPV) detection is the polymerase chain reaction (PCR) assay. However, technical requirements and associated costs preclude the worldwide use of PCR assays on a routine basis. Herein, we evaluated the predictive abilities of tumor morphology, immunohistochemistry for p16^INK4a expression, and in situ hybridization (ISH) for HR-HPV detection in defining HPV status, as established by PCR.Materials and methodsTissue samples from 48 patients with HPV-positive penile squamous cell carcinoma (SCC) were included in 4 tissue microarrays (TMA).ResultsSensitivities and specificities were as follows: tumor morphology, 70% and 68%; p16^INK4a immunohistochemistry, 65% and 90%; HR-HPV ISH, 47% and 100%. Regarding combinations of the predictors, the best performance was seen when HR-HPV ISH and p16^INK4a immunohistochemistry were combined, regardless of the tumor morphology: sensitivity, 88%; specificity, 64%; area under the receiver-operating characteristic (AUC) curve, 0.83. Combinations of tumor morphology with p16^INK4a immunohistochemistry or with HR-HPV ISH performed similarly well.ConclusionsIn penile SCC, both p16^INK4a immunohistochemistry and ISH for HR-HPV increase the predictive ability of routine morphology in defining HPV status. These tests can be interpreted differentially, depending on the necessity of a higher sensitivity or a higher specificity. For research/screening studies, we recommend combining tumor morphology, p16^INK4a immunohistochemistry, and HR-HPV ISH. To increase sensitivity, positivity in any of these predictors should be considered as indicative of HPV infection. For routine diagnosis of clinical cases, criteria should be more stringent, and, to achieve the highest specificity in classifying a case as HPV-related, all predictors should be consistently positive. The data generated in the present study could be used in algorithms for defining HPV status in penile carcinomas.     

Effects of hepatitis A vaccination on atherogenesis in a murine model

Summary. Our laboratory demonstrated that seropositivity to hepatitis A virus (HAV) independently predicts risk for coronary artery disease (CAD). As these findings are based only on the presence of HAV-specific antibodies, and not infectious virus, this prompted questions regarding possible effects of HAV vaccines on CAD development. If seropositivity to HAV alone, resulting from HAV vaccination, leads to increased atherogenesis, this raises important issues regarding the benefit of protection against HAV infection vs the risk of developing CAD. This study examines the effect of HAV vaccination on atherosclerosis development in a cholesterol-fed mouse model. Animals either received HAV vaccine, adjuvant, or saline. After 15 weeks, no significant differences were found in lesion area between the groups: HAV vaccine, 13 470 μm²; adjuvant, 16 332 μm² and saline, 14 356 μm². Only animals receiving HAV vaccination developed HAV-specific IgG. Thus, in this mouse model, vaccination against HAV does not contribute to the development of atherosclerosis.     

CALLA-positive myeloma: an aggressive subtype with poor survival

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.     

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.     

Characterization and quantitation of the circulating forms of serum transferrin receptor using domain-specific antibodies

To characterize the nature of the immunoreactive transferrin receptor in human serum, antisera were developed to peptide sequences of the extracellular domain of human transferrin receptor between amino acids 107 and 120 and the intracellular domain between amino acids 40 and 54. Antisera against the extracellular domain exhibited reactivity against both purified intact receptor and immunopurified circulating receptor, whereas antisera against the intracellular domain reacted only with intact receptor. Using competitive binding enzyme-linked immunosorbent assays, transferrin receptor in ultracentrifuged sera from normal subjects and patients with sickle cell anemia could be detected with antisera against the extracellular but not the intracellular domain. When the pellet obtained by ultracentrifugation of these sera was assayed after solubilization in 1% teric (polyoxyethylene-9-lauryl ether), only 0.6% of total serum receptor was detected in normal subjects and 3.8% in subjects with sickle cell disease. Roughly equal amounts of this pelleted immunoactivity were detected with antibodies against the extracellular and intracellular domains. These results indicate that less than 1% of transferrin receptor in normal human sera is intact receptor consistent with an exosomal origin and that virtually all circulating transferrin receptor is in the form of a truncated extracellular domain.     

Differential Disruption of Blood–Brain Barrier in Severe Traumatic Brain Injury

Background

Traumatic brain injury (TBI) is a significant cause of death and disability in young adults, but not much is known about the incidence and characteristics of blood–brain barrier (BBB) dysfunction in this group. In this proof of concept study, we sought to quantify the incidence of BBB dysfunction (defined as a cerebrospinal fluid (CSF)–plasma albumin quotient of ≥0.007) and examine the relationship between plasma and CSF levels of proteins and electrolytes, in patients with severe TBI.

Methods

We recruited 30 patients, all of whom were receiving hypertonic 20 % saline infusion for intracranial hypertension and had external ventricular drains in situ. Simultaneous CSF and blood samples were obtained. Biochemical testing was performed for sodium, osmolality, potassium, glucose, albumin, immunoglobulin-G, and total protein.

Results

Eleven patients (37 %) showed evidence of impairment of passive BBB function, with a CSF–plasma albumin quotient of ≥0.007. There were strong positive correlations seen among CSF–plasma albumin quotient and CSF–plasma immunoglobulin-G quotient and CSF–plasma total protein quotient (r = 0.967, P < 0.001 and r = 0.995, P < 0.001, respectively). We also found a higher maximum intracranial pressure (24 vs. 21 mmHg, P = 0.029) and a trend toward increased mortality (27 vs. 11 %, P = 0.33) in patients with BBB disruption.

Conclusions

In summary, passive BBB dysfunction is common in patients with severe TBI, and may have important implications for effectiveness of osmotherapy and long-term outcomes. Also, our results suggest that the CSF–plasma total protein quotient, a measurement which is readily available, can be used instead of the CSF–plasma albumin quotient for evaluating BBB dysfunction.