Retrospective Analysis of Clinical Outcomes of Stereotactic Body Radiation Therapy for Localized Prostate Cancer at an Asian Cancer Specialist Centre.

INTRODUCTION: The current treatment options for localized prostate cancer are radical prostatectomy and external beam radiotherapy (EBRT) with stereotactic body radiation therapy (SBRT) gaining interest as a treatment option compared to standard fractionation radiation therapy. This present study is a retrospective study evaluating the correlations between the biochemical efficacy, and treatment toxicity in SBRT for localized prostate cancer. METHODS: All organ-confined prostate cancer patients treated with SBRT from 2010 to 2018, at Beacon Hospital, Malaysia were included in this study. Patient demographics, dosimetric parameters, and disease information were retrospectively collected. The primary endpoint was biochemical recurrence-free survival assessed using the Phoenix definition (Nadir + 2 ng/mL). Toxicity outcomes were scored using the Radiation Therapy Oncology Group scale. RESULTS: Fourty-nine patients who met the inclusion criteria (5 low-, 13 intermediate- and 31 high-risk according to the D'amico Risk Classification) received SBRT. The most common dose regime was 34-35Gy in 5 fractions (n=18). Other dose regimes were 24Gy in 3 fractions and 25-33Gy in 5 fractions. Median follow-up was 45.4 months. The median pre-treatment prostate-specific antigen (PSA) was 11.22 ng/mL, which decreased to a median PSA of 0.1 ng/mL by 2 years post-treatment. Out of the 49 cases, only 1 case of biochemical recurrence occurred, yielding a 3- and 5-year overall survival of 100%, and a 3- and 5- year biochemical recurrence-free rate of 100% and 95.2%. Acute grade III urinary toxicities occurred in 1 (2%); whereas acute grade I urinary and rectal toxicities were seen in 22 (44.9%) and 7 (14.3%) patients respectively. Grade I and grade III late rectal toxicities occurred in 3 and 1 patients respectively, while 3 and 1 patient reported late grade I and III urethral stricture respectively. CONCLUSION: SBRT for clinically-localized and locally advanced prostate cancer provided promising outcomes with low toxicity and good biochemical control.

The Bipolar Hip: How Acetabular and Femoral Pathomorphology Affects Hip Motion in Femoral Acetabular Impingement Syndrome.

PURPOSE: To investigate the individual and combined contributions of acetabular and femoral morphology to hip range of motion (ROM) in patients with femoroacetabular impingement syndrome (FAIS) by use of computed tomography measurements and hip ROM evaluated on physical examination. METHODS: A retrospective chart and radiographic analysis of patients presenting with hip pain suggestive of FAIS was performed. The femoral neck-shaft angle, femoral version, magnitude and clock-face location of the alpha angle, midcoronal center-edge angle (CEA), midsagittal CEA, acetabular version, and McKibbin index were measured on computed tomography scans. Univariate and multivariate linear regression analyses determined which measurements correlated with hip ROM, including hip flexion as well as hip internal and external rotation with the hip in 90° of flexion. RESULTS: Two hundred hips that met the inclusion and exclusion criteria during the eligibility period were included in the analysis. The mean age was 31.9 ±10.0 years, there were 145 female patients (72%), and the mean body mass index was 25.2 ± 5.0. Multivariate linear regression analysis showed that the midsagittal CEA was the only measurement correlating with flexion (q = .031) whereas the femoral neck-shaft angle and McKibbin index were the only significant variables that correlated with external rotation (q = .031 and q < .001, respectively). Finally, the McKibbin index and maximum alpha angle were the only variables that correlated with internal rotation (q < .001 and q = .034, respectively). CONCLUSIONS: Multivariate analysis showed that combined acetabular and femoral version significantly correlated with internal and external rotation whereas femoral version in isolation did not. Increased cam morphology remained a significant contributor to reduced internal rotation but did not affect hip flexion. These data suggest that hip ROM is affected by both femoral pathomorphology and acetabular pathomorphology and that careful evaluation of both should be conducted prior to corrective osteoplasty or osteotomy. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Minimal clinically important differences in the American Shoulder and Elbow Surgeons, Simple Shoulder Test, and visual analog scale pain scores after arthroscopic rotator cuff repair.

BACKGROUND: Minimal clinically important differences (MCIDs) for different patient outcome scores have been reported for various shoulder diseases, including shoulder arthroplasty and the nonoperative treatment of rotator cuff disease. The purpose of this study was to assess the MCID for the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, the Simple Shoulder Test (SST), and a visual analog scale (VAS) measuring pain, after arthroscopic rotator cuff repair. METHODS: A total of 202 patients who underwent arthroscopic rotator cuff repair were retrospectively reviewed. ASES, SST, and VAS pain scores were collected preoperatively and at 1 year postoperatively. The MCID was then calculated via a 4-question anchor-based method. RESULTS: The MCID results for the ASES, SST, and VAS pain scores were 27.1, 4.3, and 2.4, respectively. Age at time of surgery, sex, anteroposterior tear size, and worker's compensation status were not associated with MCID values (P > .05). CONCLUSION: The MCID values determined in the current study are higher than those previously identified for the nonoperative treatment of rotator cuff disease using the same anchor questions. Use of these higher values should be considered when evaluating improvements of individual patients after rotator cuff repair, to determine comparative effectiveness of various rotator cuff repair techniques and to determine sample sizes for prospective comparative trials of rotator cuff repair methods.

Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer

@#Introduction: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene. Materials and Methods: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies. Results: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent. Conclusions: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

Arthroscopic Transtibial PCL Reconstruction: Surgical Technique and Clinical Outcomes.

PURPOSE OF REVIEW: Posterior cruciate ligament (PCL) injuries are relatively uncommon injuries. As such, there is a dearth of high-quality studies in the literature examining the operative management of PCL injuries and a lack of clear consensus on what the optimal method should be. The goal of this review was to conduct a comprehensive evaluation of recent literature and provide an evidence-based algorithm to optimize surgical decision-making and outcomes for PCL reconstruction. RECENT FINDINGS: Recent literature confirms that transtibial PCL reconstruction is a reliable and reproducible method to manage PCL injuries and results in satisfactory patient outcomes. However, there does not yet appear to be enough new, compelling information to conclusively determine an optimal method for surgical management. Our preferred method of management for operative PCL injuries is a single bundle transtibial PCL reconstruction, which is supported by the current body of literature. Future high-quality research studies are necessary to further guide treatment algorithms.

Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate

@#Introduction: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. Methods: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. Results: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). Conclusion: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity. @*@#

The role of heat shock proteins and glucose regulated proteins in cancer

Heat shock proteins (HSPs) are a family of evolutionary conserved proteins that work as molecular chaperones for cellular proteins essential for cell viability and growth as well as having numerous cyto-protective roles. They are sub-categorised based on their molecular weights; amongst which some of the most extensively studied are the HSP90 and HSP70 families. Important members of these two families; Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90), are the glucose regulated proteins (GRP). These stress-inducible chaperones possess distinct roles from that of the other HSPs, residing mostly in the endoplasmic reticulum and mitochondria, but they can also be translocated to other cellular locations. Their ability in adapting to stress conditions in the tumour microenvironment suggests novel functions in cancer. GRPs have been implicated in many crucial steps of carcinogenesis to include stabilization of oncogenic proteins, induction of tumour angiogenesis, inhibition of apoptosis and replicative senescence, and promotion of invasion and metastasis.

Accuracy of data entry of patient race/ethnicity/ancestry and preferred spoken language in an ambulatory care setting.

OBJECTIVE: To describe data collection methods and to audit staff data entry of patient self-reported race/ethnicity/ancestry and preferred spoken language (R/E/A/L) information. DATA SOURCE/STUDY SETTING: Large mixed payer outpatient health care organization in Northern California, June 2009. STUDY DESIGN: Secondary analysis of an audit planned and executed by the Department of Clinical Services. DATA COLLECTION/EXTRACTION METHODS: We analyzed concordance between patient written responses and staff data entry. PRINCIPAL FINDINGS: The data entry accuracy rate across questions was high, ranging from 92 to 97 percent. Inaccuracies were due to human error (62 percent), flaws in system design (2 percent), or some combination of both (35 percent). CONCLUSIONS: This study highlights the high accuracy of patient self-reported R/E/A/L data entry and identifies some areas for improvement in staff training and technical system design to facilitate further progress.

Population Colorectal Cancer Screening Estimates: Comparing Self-Report to Electronic Health Record Data in California.

INTRODUCTION: Population-based surveys are used to assess colorectal cancer (CRC) screening rates, but may be subject to self-report biases. Clinical data from electronic health records (EHR) are another data source for assessing screening rates and self-report bias; however, use of EHR data for population research is relatively new. We sought to compare CRC screening rates from a self-report survey, the 2007 California Health Interview Survey (CHIS), to EHR data from Palo Alto Medical Foundation (PAMF), a multi-specialty healthcare organization serving three counties in California. METHODS: Ever- and up-to-date CRC screening rates were compared between CHIS respondents (N=18,748) and PAMF patients (N=26,283). Both samples were limited to English proficient subjects aged 51-75 with health insurance and a physician visit in the past two years. PAMF rates were age-sex standardized to the CHIS population. Analyses were stratified by racial/ethnic group. RESULTS: EHR data included PAMF internally completed tests (84%), and patient-reported externally completed tests which were either confirmed (7%) or unconfirmed (9%) by a physician. When excluding unconfirmed tests, PAMF screening rates were 6-14 percentage points lower than CHIS rates, for both ever- and up-to-date CRC screening among Non-Hispanic White, Black, Hispanic/Latino, Chinese, Filipino and Japanese subjects. When including unconfirmed tests, differences in screening rates between the two data sets were minimal. CONCLUSION: Comparability of CRC screening rates from survey data and clinic-based EHR data depends on whether or not unconfirmed patient-reported tests in EHR are included. This indicates a need for validated methods of calculating CRC screening rates in EHR data.

Racial and Ethnic Variation in Lipoprotein (a) Levels among Asian Indian and Chinese Patients.

Background. Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD) in Non-Hispanic Whites (NHW). There are known racial/ethnic differences in Lp(a) levels, and the association of Lp(a) with CVD outcomes has not been examined in Asian Americans in the USA. Objective. We hypothesized that Lp(a) levels would differ in Asian Indians and Chinese Americans when compared to NHW and that the relationship between Lp(a) and CVD outcomes would be different in these Asian racial/ethnic subgroups when compared to NHW. Methods. We studied the outpatient electronic health records of 2022 NHW, 295 Asian Indians, and 151 Chinese adults age ≥18 y in Northern California in whom Lp(a) levels were assessed during routine clinical care from 2001 to 2008, excluding those who had received prescriptions for niacin (14.6%). Nonparametric methods were used to compare median Lp(a) levels. Significance was assessed at the P < .0001 level to account for multiple comparisons. CVD outcomes were defined as ischemic heart disease (IHD) (265 events), stroke (122), or peripheral vascular disease (PVD) (87). We used logistic regression to determine the relationship between Lp(a) and CVD outcomes. Results. Both Asian Indians (36 nmol/L) and NHW (29 nmol/L) had higher median Lp(a) levels than Chinese (22 nmol/L, P ≤ .0001 and P = .0032). When stratified by sex, the differences in median Lp(a) between these groups persisted in the 1761 men (AI v CH: P = .001, NHW v CH: P = .0018) but were not statistically significant in the 1130 women (AI v CH: P = .0402, NHW v CH: P = .0761). Asian Indians (OR = 2.0) and Chinese (OR = 4.8) exhibited a trend towards greater risk of IHD with high Lp(a) levels than NHW (OR = 1.4), but no relationship was statistically significant. Conclusion. Asian Indian and NHW men have higher Lp(a) values than Chinese men, with a trend toward, similar associations in women. High Lp(a) may be more strongly associated with IHD in Asian Indians and Chinese, although we did not have a sufficient number of outcomes to confirm this. Further studies should strive to elucidate the relationship between Lp(a) levels, CVD, and race/ethnicity among Asian subgroups in the USA.

Collecting patient race/ethnicity and primary language data in ambulatory care settings: a case study in methodology.

OBJECTIVE: To collect patient race/ethnicity and language (r/e/l) in an ambulatory care setting. DATA SOURCES/STUDY SETTING: The Palo Alto Medical Foundation (PAMF), December 2006-May 2008. STUDY DESIGN: Three pilot studies: (1) Comparing mail versus telephone versus clinic visit questionnaire distribution; (2) comparing the front desk method (FDM) versus exam room method (ERM) in the clinic visit; and (3) determining resource allocation necessary for data entry. DATA COLLECTION/EXTRACTION METHODS: Studies were planned and executed by PAMF's Quality and Planning division. PRINCIPAL FINDINGS: Collecting r/e/l data during clinic visits elicited the highest response rate. The FDM yielded higher response rate than the ERM. One full-time equivalent is initially necessary for data entry. CONCLUSIONS: Conducting sequential studies can help guide r/e/l collection in a short time frame.

Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome.

Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB patients appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower-stage/treatment-responsive CTCL versus higher-stage/treatment-resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted.