A Quality Improvement Project to Gain Insight Into What Helps Cancer Patients Cope During Outpatient Radiation Therapy Treatments.

Psychosocial support in cancer care has not been researched or published to the degree of physical support. This type of support includes the mental, emotional, social, and spiritual needs of patients and loved ones. This quality improvement project provides insight for those seeking understanding of what exactly helps cancer patients cope during outpatient radiation therapy treatments. The purpose of this project was to learn what practices benefit patient's coping during outpatient external radiation therapy treatments in order to increase attention given to psychosocial support of future cancer patients receiving outpatient external radiation therapy treatments. Insight from this project was used to create a resource handout for Novant Health Cancer Institute to help increase awareness, discussion, and attention to supporting outpatient radiation therapy patients emotionally and spiritually.

Primary seminal vesicle epithelioid smooth muscle neoplasm of uncertain biologic potential.

We present the case of a 73-year-old male patient who presented with obstructive urinary symptoms, pelvic pressure, and hematuria. CT imaging revealed a heterogenous prostate enlargement, and MRI demonstrated the mass to be arising from the seminal vesicle. Prostate biopsies showed benign tissue. Surgical excision was completed and pathology revealed it to be an epithelioid smooth muscle neoplasm of uncertain biologic potential. This is only the second known case of such a seminal vesicle tumour. As soft tissue sarcomas of the seminal vesicle emerge in the literature, we may develop a better understanding of their biologic behaviour and prognostic potential.

Safety and efficacy of anterior vertebral body tethering in the treatment of idiopathic scoliosis.

AIMS: Spinal fusion remains the gold standard in the treatment of idiopathic scoliosis. However, anterior vertebral body tethering (AVBT) is gaining widespread interest, despite the limited data on its efficacy. The aim of our study was to determine the clinical efficacy of AVBT in skeletally immature patients with idiopathic scoliosis. METHODS: All consecutive skeletally immature patients with idiopathic scoliosis treated with AVBT enrolled in a longitudinal, multicentre, prospective database between 2013 and 2016 were analyzed. All patients were treated by one of two surgeons working at two independent centres. Data were collected prospectively in a multicentre database and supplemented retrospectively where necessary. Patients with a minimum follow-up of two years were included in the analysis. Clinical success was set a priori as a major coronal Cobb angle of < 35° at the most recent follow-up. RESULTS: A total of 57 patients were included in the study. Their mean age was 12.7 years (SD 1.5; 8.2 to 16.7), with 95% being female. The mean preoperative Sanders score and Risser grade was 3.3 (SD 1.2), and 0.05 (0 to 3), respectively. The majority were thoracic tethers (96.5%) and the mean follow-up was 40.4 months (SD 9.3). The mean preoperative major curve of 51° (SD 10.9°; 31° to 81°) was significantly improved to a mean of 24.6° (SD 11.8°; 0° to 57°) at the first postoperative visit (45.6% (SD 17.6%; 7% to 107%); p < 0.001)) with further significant correction to a mean of 16.3° (SD 12.8°; -12 to 55; p < 0.001) at one year and a significant correction to a mean of 23° (SD 15.4°; -18° to 57°) at the final follow-up (42.9% (-16% to 147%); p < 0.001). Clinical success was achieved in 44 patients (77%). Most patients reached skeletal maturity, with a mean Risser score of 4.3 (SD 1.02), at final follow-up. The complication rate was 28.1% with a 15.8% rate of unplanned revision procedures. CONCLUSION: AVBT is associated with satisfactory correction of deformity and an acceptable complication rate when used in skeletally immature patients with idiopathic scoliosis. Improved patient selection and better implant technology may improve the 15.8% rate of revision surgery in these patients. Further scrutiny of the true effectiveness and long-term risks of this technique remains critical. Cite this article: Bone Joint J 2020;102-B(12):1703-1708.

PYGOPUS2 expression in prostatic adenocarcinoma is a potential risk stratification marker for PSA progression following radical prostatectomy.

AIMS: Prostate cancer (PrCa) is the most frequently diagnosed non-cutaneous cancer in men. Without clear pathological indicators of disease trajectory at diagnosis, management of PrCa is challenging, given its wide-ranging manifestation from indolent to highly aggressive disease. This study examines the role in PrCa of the Pygopus (PYGO)2 chromatin effector protein as a risk stratification marker in PrCa. METHODS: RNA expression was performed in PrCa cell lines using Northern and RT-PCR analyses. Protein levels were assessed using immunoblot and immunofluorescence. Immunohistochemistry was performed on tissue microarrays constructed from radical prostatectomies with 5-year patient follow-up data including Gleason score tumour staging, margin and lymph node involvement and prostate serum antigen (PSA) levels. Biochemical recurrence (BR) was defined as a postoperative PSA level of >0.2 nL. Univariate and multivariate analyses were performed using SAS and Kaplan-Meier curves using graphPad (Prism). RESULTS: In vitro depletion of PYGO2 by RNAi in both androgen receptor positive and negative PrCa cell lines attenuated growth and reduced Ki67 and 47S rRNA expression, while PYGO2 protein was localised to the nuclei of tumours as determined by immunohistochemistry. High expression levels of PYGO2 in tumours (n=156) were correlated with BR identified as PSA progression, after 7-year follow-up independent of other traditional risk factors. Most importantly, high PYGO2 levels in intermediate grade tumours suggested increased risk of recurrence over those with negative or weak expression. CONCLUSION: Our data suggest that elevated PYGO2 expression in primary prostate adenocarcinoma is a potential risk factor for BR.

Thirty-Day Reoperation and Readmission Rates After Correction of Adult Spinal Deformity via Circumferential Minimally Invasive Surgery-Analysis of a 7-Year Experience.

STUDY DESIGN: Single-center retrospective analysis of consecutive patients who have undergone circumferential minimally invasive surgery (cMIS) for correction of adult spinal deformity (ASD). OBJECTIVES: To study the rates of reoperations and readmissions within the first 30 days following cMIS for correction of ASD. BACKGROUND: Hospital readmission and reoperation rates have been emphasized as an important measure of quality and cost-effectiveness of care. However, there is little information about the readmission rates following cMIS correction of ASD. METHODS: This is a retrospective cohort study of 214 consecutive patients with ASD who underwent correction using cMIS involving at least 2 levels. Major complications encountered during surgery or within 30 days following the index procedure that needed reoperation or readmission were recorded. The primary outcomes measured were early readmission, and early reoperation. RESULTS: An average of 4 levels were fused. Nineteen complications were noted in the 30-day period following the index surgery, giving an early complication rate of 8.9%. Twelve of those complications occurred during the initial hospitalization and 7 complications occurred after the patient had been discharged home. Forty-seven percent of the complications occurred within the first 3 years of our experience, 37% in the next 2 years, and only 16% in the following 3 years. The 30-day readmission rate was 3.3%, which showed no statistically significant difference based on the number of levels fused. CONCLUSIONS: Our study delivers significant evidence that efforts to reduce hospital readmissions for ASD patients should begin by concentrating on the postoperative complications. Although minimally invasive approaches will not eliminate all complications, they may have an effect on reducing the rate of major complications, most notably the rate of postoperative infection. This in turn can lead to a substantially lower readmission and reoperation rate as is reported in our study. LEVEL OF EVIDENCE: Level IV, case series.

Defining the inherent stability of degenerative spondylolisthesis: a systematic review.

OBJECT A range of surgical options exists for the treatment of degenerative lumbar spondylolisthesis (DLS). The chosen technique inherently depends on the stability of the DLS. Despite a substantial body of literature dedicated to the outcome analysis of numerous DLS procedures, no consensus has been reached on defining or classifying the disorder with respect to stability or the role that instability should play in a treatment algorithm. The purpose of this study was to define grades of stability and to develop a guide for deciding on the optimal approach in surgically managing patients with DLS. METHODS The authors conducted a qualitative systematic review of clinical or biomechanical analyses evaluating the stability of and surgical outcomes for DLS for the period from 1990 to 2013. Research focused on nondegenerative forms of spondylolisthesis or spinal stenosis without associated DLS was excluded. The primary extracted results were clinical and radiographic parameters indicative of DLS instability. RESULTS The following preoperative parameters are predictors of stability in DLS: restabilization signs (disc height loss, osteophyte formation, vertebral endplate sclerosis, and ligament ossification), no disc angle change or less than 3 mm of translation on dynamic radiographs, and the absence of low-back pain. The validity and magnitude of each parameter's contribution can only be determined through appropriately powered prospective evaluation in the future. Identifying these parameters has allowed for the creation of a preliminary DLS instability classification (DSIC) scheme based on the preoperative assessment of DLS stability. CONCLUSIONS Spinal stability is an important factor to consider in the evaluation and treatment of patients with DLS. Qualitative assessment of the best available evidence revealed clinical and radiographic parameters for the creation of the DSIC, a decision aid to help surgeons develop a method of preoperative evaluation to better stratify DLS treatment options.

Onabotulinumtoxin A injections: a safety review of children with clubfoot under 2 years of age at BC Children's Hospital.

BACKGROUND: Pediatric indications for Onabotulinumtoxin A extend beyond treatment of skeletal muscle conditions. Each of the indications for Onabotulinumtoxin A use have adverse events reported in the past. The aim of this study was to review dverse events in children less than 2 years of age who were treated with Onabotulinumtoxin A injections as part of equinus foot deformity, in the setting of clubfoot at British Columbia's Children Hospital. METHODS: A retrospective review of all clubfoot patients at British Columbia's Children Hospital, less than 2 years of age, who received a Onabotulinumtoxin A injection for equinus correction, between September 2000 and December 2012 was conducted. Data collected included demographics, clinical diagnosis, treatment history, ankle range of motion and any adverse event noted by the clubfoot team or reported by the families. RESULTS: A total of 239 eligible subjects (361 feet) had received 523 Onabotulinumtoxin A injections before the age of 2 years. There was only one adverse event reported out of the 523 Onabotulinumtoxin A injections (adverse events rate of 0.19%) given at British Columbia's Children Hospital. However, this adverse event was not found related to the Onabotulinumtoxin A injection. CONCLUSIONS: Onabotulinumtoxin A appears to be safe with respect to the adverse events, for use in children under 2 years of age with the diagnosis of clubfoot when dosed at 10 units per kilogram. However, the dose of Onabotulinumtoxin A and underlying diagnosis should always be kept in mind.

Bioactivation of 1,1-dichloroethylene to its epoxide by CYP2E1 and CYP2F enzymes.

1,1-Dichloroethylene (DCE) exposure to mice elicits lung toxicity that selectively targets bronchiolar Clara cells. The toxicity is mediated by DCE metabolites formed via cytochrome P450 metabolism. The primary metabolites formed are DCE epoxide, 2,2-dichloroacetaldehyde, and 2-chloroacetyl chloride. The major metabolite detected is 2-S-glutathionyl acetate [C], a putative conjugate of DCE epoxide with glutathione. In this investigation, studies were undertaken to test the hypothesis that CYP2E1 and CYP2F2 are involved in bioactivation of DCE to the epoxide in murine lung. We have developed a method using liquid chromatography/mass spectrometry (LC/MS) to evaluate the kinetics of the rates of production of conjugate [C] by recombinant CYP2E1 and CYP2F enzymes and lung microsomes. Concentration-dependent formation of conjugate [C] was found in incubations of DCE with recombinant CYP2E1 and CYP2F enzymes and lung microsomes from CD-1, wild-type (mixed 129/Sv and C57BL), and CYP2E1-null mice. Recombinant rat CYP2E1 exhibited greater affinity and catalytic efficiency for DCE metabolism than did recombinant human CYP2E1, mouse CYP2F2, goat CYP2F3 or rat CYP2F4. In the lung microsomal incubations, the rates of conjugate [C] production were higher in CD-1 mice than in either wild-type or CYP2E1-null mice; the level of [C] in CYP2E1-null mice was about 66% of that in wild-type mice. These results demonstrated that LC/MS analysis is a suitable method for detection and quantitation of conjugate [C], and that CYP2E1 and CYP2F2 catalyze the bioactivation of DCE to the epoxide in murine lung. The results also demonstrated that CYP2E1 is the high-affinity enzyme involved in DCE bioactivation.

Bioactivation of 1,1-dichloroethylene by CYP2E1 and CYP2F2 in murine lung.

1,1-Dichloroethylene (DCE) exposure evokes lung toxicity with selective damage to bronchiolar Clara cells. Recent in vitro studies have implicated CYP2E1 and CYP2F2 in the bioactivation of DCE to 2-S-glutathionyl acetate [C], a putative conjugate of DCE epoxide with glutathione. An objective of this study was to test the hypothesis that bioactivation of DCE is catalyzed by both CYP2E1 and CYP2F2 in murine lung. Western blot analysis of lung microsomal proteins from DCE-treated CD-1 mice showed time-dependent loss of immunodetectable CYP2F2 and CYP2E1 protein. Dose-dependent formation of conjugate [C] was observed in the lungs of CD-1 mice treated with DCE (75-225 mg/kg), but it was not detected after pretreatment with 5-phenyl-1-pentyne (5-PIP). Treatment of mice with 5-PIP and also with diallyl sulfone (DASO2) significantly inhibited hydroxylation of p-nitrophenol (PNP) and chlorzoxazone (CHZX). Incubation of recombinant CYP2F3 (a surrogate for CYP2F2) and recombinant CYP2E1 with PNP and CHZX confirmed that they are substrates for both of the recombinant enzymes. Incubation of the recombinant enzymes with DASO2 or 5-PIP significantly inhibited hydroxylation of both PNP and CHZX. Bronchiolar injury was elicited in CD-1 mice treated with DCE (75 mg/kg), but it was abrogated with 5-PIP pretreatment. Bronchiolar toxicity also was manifested in the lungs of CYP2E1-null and wild-type mice treated with DCE (75 mg/kg), but protection ensued after pretreatment with 5-PIP or DASO2. These results showed that bioactivation of DCE in murine lung occurred via the catalytic activities of both CYP2E1 and CYP2F2 and that bioactivation by these enzymes mediated the lung toxicity.

Metabolism and toxicity of trichloroethylene in epididymis and testis.

The widespread occupational exposure to trichloroethylene (TCE) led us to test the hypothesis that TCE causes toxicity in the male reproductive system. We also investigated mechanisms mediating the potential cytotoxic response. Mice were exposed to TCE (1000 ppm) by inhalation for 6 h/day for 5 days/week for a total of 19 days. Exposure after the first week was interspersed by a "weekend." To estimate internal exposure, we measured the TCE metabolites, trichloroacetic acid (TCA) and trichloroethanol (TCOH), in urine at Days 4, 9, 14, and 19. Urinary excretion of TCOH was significantly higher than TCA; levels of TCOH and TCA significantly increased by the second and third week, respectively. Cytochrome P450 2E1 (CYP2E1), an enzyme involved in TCE metabolism, was localized in the epididymal epithelium and testicular Leydig cells, and was found at higher levels in the former than the latter. Immunoblotting confirmed that CYP2E1 protein was present in greater amounts in epididymis than in testis. p-Nitrophenol hydroxylation, a CYP2E1 catalytic activity, was also higher in the epididymis than in the testis. Chloral, a major TCE metabolite, was generated in microsomal incubations at significantly higher levels in epididymis than in testis. Antibody inhibition of CYP2E1 reduced chloral formation, which was more pronounced in epididymis than in testis. After 4 weeks of TCE exposure, damage to the epididymis was manifested as sloughing of epithelial cells. These results indicated that TCE is metabolized in the male reproductive tract, leading to adverse effects that are more severe in the epididymis than in the testis.