Skip to main content

    Ants Toi

    Serum insulin-like growth factor-I (IGF-I) levels at the higher end of the reference range have been associated with increased risk for the future development of prostate cancer. We determined whether high serum IGF-I levels are... more
    Serum insulin-like growth factor-I (IGF-I) levels at the higher end of the reference range have been associated with increased risk for the future development of prostate cancer. We determined whether high serum IGF-I levels are associated with precancerous lesions of the prostate. We conducted a case-control study to determine whether high serum IGF-I levels were associated with the presence of
    Clinical confusion continues to exist regarding the underestimation of cancers among patients on active surveillance and among men with repeated negative prostate biopsies despite worrisome prostate-specific antigen (PSA) levels. We have... more
    Clinical confusion continues to exist regarding the underestimation of cancers among patients on active surveillance and among men with repeated negative prostate biopsies despite worrisome prostate-specific antigen (PSA) levels. We have previously described our initial experience with magnetic resonance imaging (MRI)-based detection of tumours in the anterior prostate gland. In this report, we update and expand our experience with these tumours in terms of multiparametric-MRI findings, staging, and grading. Furthermore, we report early treatment outcomes with these unique cancers. We reviewed our prostate MRI dataset of 1117 cases from January 2006 until December 2012 and identified 189 patients who fulfilled criteria for prostate evasive anterior tumors (PEATS). Descriptive analyses were performed on multiple covariates. Kaplan-Meier actuarial technique was used to plot the treatment-related outcomes from PEATS tumours. Among the 189 patients who had MRI-detectable anterior tumours, 148 had biopsy proven disease in the anterior zone. Among these tumours, the average PSA was 18.3 ng/mL and most cancers were Gleason 7. In total, 68 patients chose surgical therapy. Among these men, most of their cancers had extra prostatic extension and 46% had positive surgical margins. Interestingly, upgrading of tumours that were biopsy Gleason 6 in the anterior zone was common, with 59% exhibiting upgrading to Gleason 7 or higher. Biochemical-free survival among men who elected surgery was not ideal, with 20% failing by 20 months. PEATS tumours are found late and are disproportionally high grade tumours. Careful consideration to MRI testing should be given to men at risk for PEATS.
    ABSTRACT Background: Antimicrobial prophylaxis prior to transrectal ultrasound (TRUS)-guided prostate biopsy reduces the risk of infectious complications. Despite increasing E. coli resistance to fluoroquinolones, oral ciprofloxacin... more
    ABSTRACT Background: Antimicrobial prophylaxis prior to transrectal ultrasound (TRUS)-guided prostate biopsy reduces the risk of infectious complications. Despite increasing E. coli resistance to fluoroquinolones, oral ciprofloxacin remains the most widely used agent for this indication. We reviewed the temporal trends of infection-related complications following TRUS-guided prostate biopsy at Princess Margaret Cancer Center, a Canadian tertiary care hospital where ciprofloxacin prophylaxis is used. Methods: Surveillance for complications following TRUS-guided prostate biopsy at our center has been conducted since 2003. Complications that occurred within 30-days of the procedure were included. Definite infections were defined as either a positive blood or urine culture in a patient meeting National Healthcare Safety Network (NHSN) criteria for bloodstream or urinary tract infection, respectively. Possible infections were defined as empiric treatment for cystitis, pyelonephritis, prostatitis, epididymo-orchitis, or sepsis without culture confirmation. Results: Of 19279 men who underwent TRUS-guided prostate biopsy between 2003 and 2013, 159 (0.8%) developed infectious complications. Between 2006 and 2013, definite urinary tract infection increased from 0.05% to 0.8% (p<.0001); bloodstream infections increased from 0.1% to 0.6% (p<0.0001); and overall infections, including definite and possible infections, increased from 0.3% to 1.9% (p<.0001) (Figure). E. coli represented (85/89) 95% of isolates from urine and blood cultures of which 93% were resistant to ciprofloxacin. Resistance of E. coli to trimethoprim/sulfamethoxazole, gentamicin, cefazolin, ceftriaxone, and nitrofurantoin was 58%, 42%, 33%, 32%, and 8%, respectively. Conclusion: The proportion of TRUS-guided prostate biopsies associated with infectious complications has increased significantly over the past decade, likely driven by the emergence of E. coli resistance to ciprofloxacin. Emerging antibiotic resistance may make current prophylaxis strategies with ciprofloxacin less effective, emphasizing the need for prospective evaluation of other prophylactic regimens and other non-antibiotic prevention strategies.
    The human kallikrein-2 (hK2) protein and two single nucleotide polymorphism (SNPs) (rs2664155, rs198977) of the gene are associated with prostate cancer risk. We examined whether hK2 protein and gene SNPs predict prostate cancer at the... more
    The human kallikrein-2 (hK2) protein and two single nucleotide polymorphism (SNPs) (rs2664155, rs198977) of the gene are associated with prostate cancer risk. We examined whether hK2 protein and gene SNPs predict prostate cancer at the time of repeat biopsy. We prospectively offered a repeat biopsy to men with a negative prostate biopsy performed for a PSA >4.0 ng/mL or abnormal Digital Rectal Exam (DRE) between 2001-2005. We genotyped and measured serum hK2 levels in 941 men who underwent a repeat prostate biopsy. Logistic regression analyses were conducted to determine the significance of KLK2 SNPs and hK2 levels for predicting cancer at repeat biopsy. Of the 941 patients, 180 (19.1%) were found to have cancer. The rs198977 SNP was positively associated with cancer at repeat biopsy (OR variant T allele = 1.8, 95% CI: 1.04-3.13, p = 0.049). When combined, the odds ratio for prostate cancer for patients with high hK2 levels and the variant T-allele of rs198977 was 3.77 (95% CI: 1...
    Active surveillance (AS) is an expectant management strategy for prostate cancer (PCa). The impact of obesity on progression is not well characterized in this population. To determine if obesity is associated with progression in men on AS... more
    Active surveillance (AS) is an expectant management strategy for prostate cancer (PCa). The impact of obesity on progression is not well characterized in this population. To determine if obesity is associated with progression in men on AS for low-risk PCa. Men undergoing AS for low-risk PCa (no Gleason pattern ≥4, three or fewer cores involved or one-third or less of the total number of cores involved, and no core with >50% cancer involvement) were identified at our institution. The outcomes were pathologic progression (defined as no longer meeting low-risk criteria on follow-up biopsy) and therapeutic progression (defined as intent to initiate active treatment). Kaplan-Meier curves and multivariable logistic regression and Cox proportional hazards models were used, with separate models for reclassification at confirmatory biopsy (first biopsy after diagnostic biopsy) and progression beyond confirmatory biopsy. In this cohort of 565 men (median follow-up: 48 mo), 124 (22%) were o...
    To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of prostate cancer (PC) detection in men undergoing biopsy. Men were identified using our academic institution's prospectively maintained... more
    To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of prostate cancer (PC) detection in men undergoing biopsy. Men were identified using our academic institution's prospectively maintained prostate biopsy database. Patients were classified as aspirin (ASA) users, users of other NSAIDs, or nonusers. The primary outcome was any PC on biopsy, and the secondary outcome was clinically significant PC (CSPC; Gleason sum ≥7). Multivariate logistic regression analyses were performed to adjust for a priori defined clinical confounders. Of 839 patients, 408 (48.6%) were diagnosed with PC and 201 (24.0%) had CSPC. A higher proportion of ASA users (63.5%) and other NSAID users (61.2%) had PC compared with nonusers (41.9%; P <.001). CSPC was more common among ASA users (34.9%; P <.001) compared with other NSAID users (20.0%) and nonusers (20.9%). In multivariate regression analyses, ASA use (odds ratio [OR] = 2.04; 95% confidence interval [C...
    To determine if the USPSTF recommendation against PSA screening was associated with a change in biopsy and cancer detection rates. We conducted a time series analysis (10/2008-06/2013) of prostate biopsies performed at University Health... more
    To determine if the USPSTF recommendation against PSA screening was associated with a change in biopsy and cancer detection rates. We conducted a time series analysis (10/2008-06/2013) of prostate biopsies performed at University Health Network (Toronto). Biopsies for active surveillance or solely targeting MRI-detected lesions were excluded. Interventional auto-regressive integrated moving average (ARIMA) models with step functions were used to examine changes in the number of biopsies performed and cancers detected per month. Low risk PC (LRPC) was defined as no Gleason pattern ≥4, ≤3 cores involved or ≤1/3 of total number of cores involved, and no core with >50% cancer involvement. Intermediate-to-high grade PC (I-HGPC) was defined as Gleason 7-10. A total of 3408 biopsies were performed and 1601 (47.0%) PCs were detected (LRPC=563 (16.5%); I-HGPC=914 (26.8%)). The median number of biopsies per month decreased from 58.0 (IQR=54.5-63.0) before recommendations to 35.5 (IQR=27.0-...
    The diastrophic dysplasia family of osteochondrodysplasias comprises a spectrum of skeletal diseases characterized by abnormal growth and remodelling of cartilage and bone. They are caused by mutations in the diastrophic dysplasia sulfate... more
    The diastrophic dysplasia family of osteochondrodysplasias comprises a spectrum of skeletal diseases characterized by abnormal growth and remodelling of cartilage and bone. They are caused by mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene. Different defects in this gene product give rise to the variety of phenotypes based on the level of residual transport capacity. We reported a case
    We report the prenatal findings in two cases of Beals syndrome. Both pregnancies presented with clinical features of arthrogryposis multiplex congenita/fetal akinesia syndrome (AMC/FAS), including clenched fists and multiple joint... more
    We report the prenatal findings in two cases of Beals syndrome. Both pregnancies presented with clinical features of arthrogryposis multiplex congenita/fetal akinesia syndrome (AMC/FAS), including clenched fists and multiple joint contractures on repeat prenatal ultrasound examinations. The first case was diagnosed as having Beals syndrome on physical examination shortly after birth and the diagnosis was confirmed by DNA analysis, shown as a point mutation in the fibrillin 2 (FBN2) gene. The second case was diagnosed with Beals syndrome following microarray analysis on amniocytes, which showed a deletion of the FBN2 gene. Although most cases with AMC/FAS carry a poor prognosis, Beals syndrome is consistent with normal cognitive development and a better prognosis. Thus, making the correct diagnosis is crucial, both pre- and postnatally, for accurate counseling and management.
    To prospectively evaluate toxicity, biochemical failure-free survival (bFFS) and biopsy-proven local control for prostate cancer patients treated with 75.6 Gy in 42 fractions using 6-field conformal radiotherapy to prostate alone. From... more
    To prospectively evaluate toxicity, biochemical failure-free survival (bFFS) and biopsy-proven local control for prostate cancer patients treated with 75.6 Gy in 42 fractions using 6-field conformal radiotherapy to prostate alone. From 1997 to 1999, 140 patients with T1-2NxM0, Gleason score<or=8, and PSA<or=20 ng/ml prostate cancer were assessed using Radiation Therapy Oncology Group acute and late toxicity scores. bFFS was determined for 120 patients treated without hormones. Post-treatment prostate biopsies were performed at a median of 3 years and a late toxicity questionnaire was administered at a median of 5 years. Clinically important acute toxicities were gastrointestinal (GI) grade 2: 22% and 3: 0%, and genitourinary (GU) grade 2: 24% and 3: 2%. Late physician-assessed toxicities were GI>or=grade 2: 2%, and GU>or=grade 2: 1%. The 3-year bFFS of patients failure-free before biopsy was 93% (95% CI: 83-100) from a negative biopsy and 22% (95% CI: 0-56) from a positive biopsy (P=0.001). Patients reported significantly more late toxicity than physicians (GI: P=0.003, GU: P<0.001). At 5.0 years median follow-up, cause-specific survival was 98% (95% CI: 96-100), overall survival was 91% (95% CI: 86-97), and bFFS was 55% (95% CI: 45-64). 75.6 Gy caused modest levels of acute and late toxicity. Three-year biopsies predicted subsequent biochemical outcome.
    Transrectal ultrasound and ultrasound guided prostate biopsy is the current standard for detecting prostate cancer. Newer techniques such as elastography and contrast enhanced ultrasound may help in lesion detection and monitoring.... more
    Transrectal ultrasound and ultrasound guided prostate biopsy is the current standard for detecting prostate cancer. Newer techniques such as elastography and contrast enhanced ultrasound may help in lesion detection and monitoring. Advances are occurring in several areas including multiparametric MRI, understanding of the nature of prostate cancer and new therapies including focal therapy and active surveillance. These changes are creating an increasing role for targeted biopsies following MRI and for use of MRI for treatment monitoring.
    The cerebral cortex develops in three overlapping stages: cell proliferation, neuronal migration, and cortical organization. Abnormal neuronal migration may result in lissencephaly, which is characterized by either the absence (agyria) or... more
    The cerebral cortex develops in three overlapping stages: cell proliferation, neuronal migration, and cortical organization. Abnormal neuronal migration may result in lissencephaly, which is characterized by either the absence (agyria) or the paucity (pachygyria) of cerebral convolutions. The two main clinicopathologic types of lissencephaly may be differentiated according to their prenatal imaging features. Other cranial and extracranial abnormalities also may occur in association with lissencephaly. The prognosis is often poor, but prenatal diagnosis allows appropriate counseling and optimization of obstetric management. Familiarity with the normal ultrasonographic (US) and magnetic resonance (MR) imaging appearances of the fetal cerebral cortex at various stages of gestation is essential for the early detection of abnormal sulcal development. The primary fissures and sulci that can be examined with prenatal US and MR imaging include the parieto-occipital fissure, calcarine fissure, cingulate sulcus, convexity sulci, and sylvian fissure and insula.
    Ultrasonography (US) is performed during early pregnancy for dating, determination of the number of fetuses, assessment of early complications, and increasingly for evaluation of the fetus, including measurement of the thickness of the... more
    Ultrasonography (US) is performed during early pregnancy for dating, determination of the number of fetuses, assessment of early complications, and increasingly for evaluation of the fetus, including measurement of the thickness of the nuchal translucency (NT). Measurement of NT thickness between 11 and 14 weeks gestation, combined with maternal age and maternal serum biochemistry, can be an effective method of screening for trisomy 21 and other chromosomal abnormalities. Furthermore, an increased NT thickness in the presence of a normal karyotype is associated with an increased frequency of structural defects and genetic syndromes. Therefore, this finding is an indication for a more detailed anatomic survey of the fetus. Besides nuchal abnormalities, a wide range of other congenital anomalies can be diagnosed with US at 11-14 weeks gestation, including defects of the central nervous system, heart, anterior abdominal wall, urinary tract, and skeleton. The anatomic survey can be performed with a standardized protocol by using transabdominal US and, when necessary, transvaginal US. A thorough knowledge of the US features of normal fetal development is necessary to avoid potential diagnostic pitfalls.
    We describe the finding of cavum veli interpositi (CVI) on fetal ultrasound and MRI and the postnatal MRI and developmental follow-up in two cases. The first case was diagnosed on fetal ultrasound at 33... more
    We describe the finding of cavum veli interpositi (CVI) on fetal ultrasound and MRI and the postnatal MRI and developmental follow-up in two cases. The first case was diagnosed on fetal ultrasound at 33 weeks' gestation and confirmed on fetal MRI. No abnormalities were detected on postnatal examinations and the brain MRI at 1 year of age showed no changes. At 4 years of age, his growth and development were normal.The second case was diagnosed with CVI on fetal ultrasound and MRI at 33.5 weeks' gestation. Postnatal examination showed no abnormalities, and brain MRI at 8 months of age revealed that the CVI was unchanged, but there was a dilated cavum septum pellucidum and cavum vergae. Her growth and development during the first 4 years of life were normal. CVI is a rare fetal ultrasound finding, which seems to be benign. However, further neurodevelopmental follow-up is needed to confirm this observation.
    Congenital cardiac diverticula are rare abnormalities that may occur as isolated malformations. In this report, we describe a case of an isolated congenital cardiac diverticulum complicated by a large serous pericardial effusion diagnosed... more
    Congenital cardiac diverticula are rare abnormalities that may occur as isolated malformations. In this report, we describe a case of an isolated congenital cardiac diverticulum complicated by a large serous pericardial effusion diagnosed ultrasonographically at 19 weeks' gestation. Therapeutic pericardiocentesis at 20 weeks' gestation resulted in complete resolution of the effusion with a normal fetal outcome. There is only one previous report of a prenatal diagnosis of a cardiac diverticulum complicated by a pericardial effusion and that patient underwent termination of pregnancy (Carles et al., 1995). Given the otherwise favourable prognosis for this lesion, and the excellent response in this case, pericardiocentesis should be considered in similar cases.
    We report a patient diagnosed prenatally on routine fetal ultrasound, at 30 weeks' gestation, with subdural haemorrhage. The mother had suffered a mild abdominal trauma and had Factor XI deficiency; however, both were felt to be... more
    We report a patient diagnosed prenatally on routine fetal ultrasound, at 30 weeks' gestation, with subdural haemorrhage. The mother had suffered a mild abdominal trauma and had Factor XI deficiency; however, both were felt to be aetiologically insignificant. Prenatal follow-up ...
    The objective of this study is to describe the prenatal sonographic features and the results of DNA analysis on three fetuses with dyssegmental dysplasia, Silverman-Handmaker type (DD-SH). A retrospective review of three fetuses with... more
    The objective of this study is to describe the prenatal sonographic features and the results of DNA analysis on three fetuses with dyssegmental dysplasia, Silverman-Handmaker type (DD-SH). A retrospective review of three fetuses with confirmed DD-SH was conducted. The fetal ultrasound findings, the radiological characteristics, and the results of the mutation analysis of the heparan sulphate perlecan gene 2 (HSPG2) were reviewed. There were three cases in two families with DD-SH diagnosed prenatally. The main prenatal ultrasound and the radiological features of DD-SH were severe limb shortening and vertebral segmentation and fusion defects (anisospondyly). The DNA analysis of the HSPG2 gene showed that the two affected fetuses in a nonconsanguineous family had a compound heterozygote for the c.646G > T transversion in exon 7 and a c.5788C > T transition in exon 46. The fetus born to the consanguineous couple had a homozygous mutation c.1356-27_1507 + 59del. DD-SH can be diagnosed prenatally using fetal ultrasound as early as 13 weeks. Xrays and DNA analysis of the HSPG2 gene are important for the confirmation of the diagnosis and for the preimplantation and prenatal diagnosis in pregnancies at risk.
    To determine the visualization rates of fetal anatomic structures by three-dimensional ultrasound (3DUS) at 12-13 weeks of gestation. This was a prospective observational study of women presenting for nuchal translucency ultrasound. Five... more
    To determine the visualization rates of fetal anatomic structures by three-dimensional ultrasound (3DUS) at 12-13 weeks of gestation. This was a prospective observational study of women presenting for nuchal translucency ultrasound. Five 3D volumes of the fetus were acquired transabdominally. Two investigators independently reviewed the stored volumes offline following a standardized protocol. One hundred singleton fetuses were examined. The mean time for 3D volumes acquisition was 4.8 min; and for 3D review 17 min. Anatomic structures were seen as follows: cranium, lateral cerebral ventricles and abdominal wall 100%; stomach, vertebrae, upper and lower limbs >or= 94%; face 71%, bladder 58%, both kidneys 39%, skin overlying spine 26% and heart 18%. Agreement between two observers ranged from 100% (for head, abdominal wall and lower limbs) to 43% (for visualization of skin overlying spine). A complete basic anatomic survey was achieved in 11.4% of the 12-week fetuses and 33.3% of the 13-week fetuses (p-value = 0.038). First-trimester transabdominal 3DUS was adequate for assessment of the head, abdominal wall, stomach, limbs and vertebral alignment. It was less effective for evaluating the heart and intactness of the skin over the spine.
    Document patient choices and screening performance (false positive and detection rates) when three improved Down syndrome screening protocols were introduced coincidentally. Second-trimester... more
    Document patient choices and screening performance (false positive and detection rates) when three improved Down syndrome screening protocols were introduced coincidentally. Second-trimester 'triple marker' screening was expanded by adding second-trimester dimeric inhibin-A (four-marker), with or without first-trimester pregnancy-associated plasma protein-A (five-marker). Nuchal translucency (NT) measurements were included when available from accredited sonographers (six-marker). For assigning risk, two sets of marker distribution parameters were evaluated. Over 3.5 years, 8571 women enrolled (median age 30.6 years). Uptake of the four-, five- and six-marker protocols was 18%, 46% and 36%, respectively. Of those selecting an integrated test (five or six markers), 9.7% did not provide the second trimester serum sample. False positive rates decreased with added markers (5.2%, 5.1% and 2.5%, respectively) and varied between the two parameter sets, while detection remained high. Overall, 21 of 23 cases were detected (91%, 95% CI 73-98%) at a 4.2% false positive rate (95% CI 3.3-5.1%). Integrated screening protocols were chosen 4.6 times more often than four-marker screening (82% vs. 18% uptake). Overall detection was higher and false positives lower, consistent with recent guidelines. Important performance factors include gestational dating method, risk cut-off, and the parameter set used to assign risk.
    The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided... more
    The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided biopsy is artifactually associated with prostate volume. We evaluated our institutional data set of TRUS guided biopsies in the last 3 years and identified 369 cases of prostate cancer that fit the criteria of PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens from the same patients using univariate and multiple logistic regression analyses. Assessed covariates included patient age, PSA and TRUS volume. Risk factors for Gleason pattern 4 or greater in the biopsy specimens included age (p = 0.01), hypoechoic lesions on TRUS (p <0.001) and TRUS volume (p = 0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant of Gleason pattern 4 or greater on multivariable analysis. Although prostate volume was a predictor for biopsy derived high grade disease it was not predictive of true histological grade. These data suggest that simply having a larger prostate results in fewer high grade cancers diagnosed at biopsy. Prostatectomy results in the same men suggest sampling artifact, as the distribution of cancer grade is not associated with prostate volume. These findings provide evidence that the increase in higher grade tumors among men in the finasteride arm of PCPT may simply result from prostate volume reduction.

    And 32 more