Post-prostatectomy adjuvant androgen deprivation therapy- Current opinions and practices of Canadian urologists.

INTRODUCTION: Despite the proven benefit of adjuvant androgen deprivation therapy (ADT) for patients receiving primary radiation, there are few studies evaluating adjuvant ADT after prostatectomy. In the absence of evidence, opinions and practice patterns vary. We surveyed Canadian prostate cancer surgeons about their use of adjuvant ADT and their opinions on the design of a potential adjuvant ADT trial. METHODS: An electronic survey was devised and distributed using a modified Dillman approach. The survey was sent to 38 Canadian urologists that perform radical prostatectomy and representing all 17 major academic institutions in Canada and all 10 Canadian provinces. Reminders were sent three and four weeks following the original request. In addition to demographic information, we asked surgeons about their current use of postoperative adjuvant ADT and their opinion about the need for a clinical trial. To inform trial design, we asked respondents their opinions about which patients should be eligible, what duration of ADT was most appropriate, and which outcomes are clinically meaningful. The survey was sent in February 2020 and all responses were received by March 2020. RESULTS: All 38 (100%) invited urologists completed the survey. Only 3 (7%) respondents currently offer postoperative adjuvant ADT as an option for patients without metastases. 35 (92%) urologists believed that a trial is needed before short-term adjuvant treatment should be offered to prevent recurrence. 15 (45%) urologists believed an adjuvant ADT trial was most appropriate for patients with an estimated PSA recurrence risk of >25% and 16 (42%) believed a recurrence risk of >50% was most appropriate. 25 (66%) respondents believed 12-month was the optimal duration of treatment with adjuvant ADT for a randomized trial. 37 (97%) respondents felt that prolonging the time to PSA recurrence and/or pelvic radiation was a clinically important outcome. The majority (20; 53%) of respondents would recommend 12 months of adjuvant ADT in their practice if a randomized trial showed a 50% relative risk reduction in PSA recurrence at 5-year postoperative. CONCLUSION: The vast majority of Canadian prostate cancer surgeons do not offer adjuvant ADT following prostatectomy in patients without metastases. Based on the results from this survey, a randomized trial was considered warranted and feasible, and would influence patient care.

Lysine analogue use during cancer surgery: a survey from a Canadian tertiary care centre.

Background: When used during surgery, antifibrinolytic hemostatic agents such as lysine analogues are effective at reducing blood loss and the need for transfusions. Despite proven efficacy, use of hemostatic agents remains low during some surgeries. Our objective was to explore surgeon opinions about, and use of lysine analogues in, oncologic surgeries at a large tertiary care academic institution. Methods: We administered a survey to surgeons who perform high-transfusion-risk oncologic surgeries at a large academic hospital in Ottawa, Ontario. Design and distribution of the survey followed a modified Dillman method. To ensure that the survey questionnaire was relevant, clear, and concise, we performed informant interviews, cognitive interviews, and pilot-testing. The final survey consisted of 19 questions divided into 3 sections: respondent demographics, use of hemostatic agents, and potential clinical trial opinions. Results: Of 28 surgeons, 24 (86%) participated. When asked to indicate the frequency of lysine analogue use, "never" accounted for 46% of the responses, and "rarely" (<10% of the time) accounted for 23% of the responses. Reasons for never using included "unfamiliar with benefits" and "prefer alternatives." Fifteen surgeons (63%) felt that a trial was needed to demonstrate the efficacy and safety of lysine analogues in their cancer field. Conclusions: Our survey found that lysine analogues are infrequently used during oncologic surgeries at our institution. Many surgeons are unfamiliar with the benefits and side effects of lysine analogues and, alternatively, use topical hemostatic agents. Our results demonstrate that future trials exploring the efficacy and safety of lysine analogues in oncologic surgery are needed.

Soft Tissue Special Issue: Chondroid Neoplasms of the Skull.

Clinically, radiologically, and pathologically, chondroid neoplasms of the skull can be diagnostically challenging due to overlapping features in each of these domains. Compounding the problem for the pathologist, there is also significant morphologic, immunophenotypic, and molecular genetic overlap between benign and malignant cartilaginous lesions, and the majority of these lesions are encountered quite rarely in routine surgical pathology practice. Each of these factors contribute to the diagnostic difficulty posed by these lesions, highlighting the importance of radiologic-pathologic correlation in the diagnosis. This review is intended to provide an update for surgical pathologists on some of the most commonly encountered chondroid neoplasms in the skull, and includes the following lesions: chondromyxoid fibroma, synovial chondromatosis, chondrosarcoma and variants, and chordoma and variants. For each of these lesions, the differential diagnosis and useful ancillary tests will be discussed in the context of a broad range of additional primary and secondary lesions.

Ear and Temporal Bone Pathology: Neural, Sclerosing and Myofibroblastic Lesions.

Neural, sclerosing, and myofibroblastic lesions of the ear and temporal bone present diagnostic challenges for both clinicians and pathologists due to significant overlap in their clinical presentations, histologic appearances, and immunohistochemical profiles. While some of these lesions, such as schwannomas, are relatively common, others are rendered even more difficult because they are encountered very rarely in routine surgical pathology practice. This review is intended to provide an update on the pathology of some of the most commonly encountered primary diagnostic entities for the ear and temporal bone, and includes the following neural lesions: schwannoma, meningioma, and encephalocele/meningocele. Sclerosing lesions that will be discussed include spindle cell and sclerosing rhabdomyosarcoma, sclerosing epithelioid fibrosarcoma, and sclerosing paraganglioma. Finally, myofibroblastic lesions that will be reviewed are nodular fasciitis, IgG4-related disease, and solitary fibrous tumor. For each of these lesions, the differential diagnosis and useful ancillary tests will be discussed in the context of a broad range of additional primary and secondary lesions.

Site-directed mutagenesis of acyl carrier protein (ACP) reveals amino acid residues involved in ACP structure and acyl-ACP synthetase activity.

Acyl carrier protein (ACP) interacts with many different enzymes during the synthesis of fatty acids, phospholipids, and other specialized products in bacteria. To examine the structural and functional roles of amino acids previously implicated in interactions between the ACP polypeptide and fatty acids attached to the phosphopantetheine prosthetic group, recombinant Vibrio harveyi ACP and mutant derivatives of conserved residues Phe-50, Ile-54, Ala-59, and Tyr-71 were prepared from glutathione S-transferase fusion proteins. Circular dichroism revealed that, unlike Escherichia coli ACP, V. harveyi-derived ACPs are unfolded at neutral pH in the absence of divalent cations; all except F50A and I54A recovered native conformation upon addition of MgCl(2). Mutant I54A was not processed to the holo form by ACP synthase. Some mutations significantly decreased catalytic efficiency of ACP fatty acylation by V. harveyi acyl-ACP synthetase relative to recombinant ACP, e.g. F50A (4%), I54L (20%), and I54V (31%), whereas others (V12G, Y71A, and A59G) had less effect. By contrast, all myristoylated ACPs examined were effective substrates for the luminescence-specific V. harveyi myristoyl-ACP thioesterase. Conformationally sensitive gel electrophoresis at pH 9 indicated that fatty acid attachment stabilizes mutant ACPs in a chain length-dependent manner, although stabilization was decreased for mutants F50A and A59G. Our results indicate that (i) residues Ile-54 and Phe-50 are important in maintaining native ACP conformation, (ii) residue Ala-59 may be directly involved in stabilization of ACP structure by acyl chain binding, and (iii) acyl-ACP synthetase requires native ACP conformation and involves interaction with fatty acid binding pocket residues, whereas myristoyl-ACP thioesterase is insensitive to acyl donor structure.