The need for, and utilization of prostate-bed radiotherapy after radical prostatectomy for patients with prostate cancer in British Columbia

Introduction:

Three randomized trials have demonstrated that post-radical prostatectomy (RP) radiotherapy decreases biochemical relapse for those with adverse pathology. Our purpose was to describe the incidence of pathologic risk factors for recurrence in a contemporary series of patients treated with RP and to describe the use of post-RP radiotherapy.

Methods:

All incident prostate cancers diagnosed between January 2005 and December 2007 were identified from the tumour registry. Cases were then linked to radiotherapy records which included dose and modality (external beam radiotherapy and brachytherapy). The pathology reports in the tumour registry were reviewed for pathologic stage, grade and margin status.

Results:

We identified 9223 patients with prostate cancer. Overall, 36.3% of patients treated with RP had positive margins, and may have benefited from adjuvant radiotherapy. After RP, 332 (15%) patients had radiotherapy to the prostate bed; of these, only 25 (1.1%) received truly adjuvant radiotherapy (delivered within 6 months with a prostate-specific antigen of <0.2 ng/mL). Of the 2181 patients treated with RP, 270 (12%) were seen by a radiation oncologist within 6 months of RP. Of the 1015 patients (47%) with adverse RP pathology (positive margins, extracapsular extension or seminal vesicle invasion), 230 (23%) were seen by a radiation oncologist within 6 months of RP.

Conclusion:

Not all patients with adverse prostatectomy pathology were seen by a radiation oncologist post-prostatectomy, and very few received adjuvant radiotherapy despite almost half of them having risk factors for relapse. See related article on page 95.     

Surgical Planning for Flexor Digitorum Longus Tendon Transfers: An Anatomic Study

Posterior tibial tendon dysfunction is often coupled with various degrees of hindfoot valgus and equinus. Preoperative planning is essential to appropriate procedure choice and surgical efficiency. The purpose of the present study was to assess the anatomy at the harvest site for flexor digitorum longus tendon transfer, specifically at the master knot of Henry. Thirty fresh-frozen below-the-knee cadavers were used for dissection. A standard anatomic approach was performed for posterior tibial tendon debridement and flexor digitorum longus tendon transfer. The flexor digitorum longus tendon was harvested and measured at the master knot of Henry. The present anatomic study evaluated the tendon width of the flexor digitorum longus tendon at a common harvest site. Of the 30 specimens, 20 (67%) measured 5 mm and 10 (33%) measured 4 mm. A 5.0-mm interference screw would be acceptable in each specimen and therefore would be the safest choice. A 4.0-mm interference screw would be acceptable in only 33% of the specimens. Males have a slightly more robust flexor digitorum longus tendon than females at the harvest site. This information will assist surgeons in preoperative planning during stage II flatfoot correction for posterior tibial tendon dysfunction.     

Efficacy of Alendronate for the Prevention of Bone Loss in Calcar Region Following Total Hip Arthroplasty

Background

Bone mineral density (BMD) loss around femoral implants, particularly in the proximal femur, is a common outcome after total hip arthroplasty. Previous studies reported the prevention of postsurgical decrease in BMD with the use of osteoporosis drug therapy. This randomized study evaluated the efficacy of alendronate and alfacalcidol for preserving BMD over a long-term follow-up.

Clusterin knockdown using the antisense oligonucleotide OGX-011 re-sensitizes docetaxel-refractory prostate cancer PC-3 cells to chemotherapy

OBJECTIVES

To characterize changes in secretory clusterin (sCLU) expression in prostate cancer cells after treatment with docetaxel and to determine whether sCLU knockdown can re‐introduce chemosensitivity in a docetaxel‐resistant, androgen‐independent human prostate cancer model.

PATIENTS AND METHODS

A tissue microarray was constructed for 84 radical prostatectomy (RP) specimens from a multicentre Phase II trial of neoadjuvant combined androgen ablation and docetaxel (CUOG‐P01a) and assessed for changes in the expression of the cytoprotective chaperone sCLU. The human prostate cancer cell line PC‐3 was repeatedly exposed to docetaxel chemotherapy in vitro, and a docetaxel‐resistant cell subline (PC‐3dR) was developed and analysed.

RESULTS

sCLU levels were significantly higher in RP specimens treated with neoadjuvant combined androgen ablation and docetaxel than in untreated specimens. Similarly, sCLU expression increased 2.5‐fold in the newly developed docetaxel‐refractory PC‐3dR cell line compared with parental PC‐3 cells. There was a dose‐dependent and sequence‐specific decrease in sCLU levels in PC‐3dR cells using OGX‐011, an antisense oligonucleotide against human sCLU. OGX‐011 and small‐interference RNA both chemosensitized PC‐3dR cells to docetaxel and mitoxantrone in vitro and apoptotic rates in PC‐3dR cells were significantly increased when OGX‐011 was combined with docetaxel. In vivo, growth of PC‐3dR xenografts in nude mice was synergistically inhibited by OGX‐011 combined with paclitaxel or mitoxantrone (by 76% and 44% compared with their mismatch controls, respectively).

CONCLUSION

The present findings indicate that targeted knockdown of sCLU enhances the effects of cytotoxic chemotherapy in docetaxel‐refractory cells, and provide preclinical proof of principle for clinical trials testing OGX‐011 in second‐line chemotherapy regimens for patients with docetaxel‐refractory prostate cancer.     

The Canadian Benign Prostatic Hyperplasia Audit Study (CanBas)

Objective

To determine the prevalence, diagnostic patterns and management of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in Canadian urology outpatient practice.

Methods

Representative urologists were randomly selected from lists provided by the Canadian and Quebec Urological Associations. Each patient identified with a BPH diagnosis during a typical 2-consecutive-week period during April, May or June 2007 was asked to complete a corresponding International Prostate Symptom Score (IPSS) questionnaire. Each day, the participant urologist completed an outpatient log and a detailed programmed chart review to transcribe demographics, investigations and treatments associated with each BPH patient.

Results

Eighty-six urologists were invited to participate. Thirty-eight (44.2%) agreed, and 27 of those (71.1%) submitted evaluable data for the audit. Of the 5616 patients seen in outpatient practice (average 208 per urologist), 4324 (77%) were male. A BPH diagnosis was identified in 19.6% of the men (n = 849; mean age 69.5, standard deviation [SD] 10, yr; age range 40–100 yr; mean duration of symptoms 4.8, SD 4.2, yr; mean IPSS score 12.3, SD 7.4; mean prostate specific antigen [PSA] 3.9, SD 3.9, ng/mL). Twenty-four percent of patients had prostates that were rated as large, 50% as medium and 26% as small. PSA level correlated positively with prostate volume. Twenty-two percent were initial consultations for LUTS and 78% were repeat visits. Diagnostic evaluation tended to follow those examinations and tests recommended by the Canadian BPH guidelines. Treatment choices tended to follow an evidence-based algorithm with respect to treatment choices for men in the various prostate-volume and PSA groups.

Conclusion

This prospective audit indicates that BPH remains a common condition managed by urologists in outpatient practice. Investigations and treatments confirm that Canadian urologists appear to be following Canadian BPH guidelines as well as the most recent evidence from the literature.     

The usefulness of the three-dimensional enhanced T1 high-resolution isotropic volume excitation MR in the evaluation of shoulder pathology: comparison with two-dimensional enhanced T1 fat saturation MR

Objective:

To evaluate the diagnostic accuracy of three-dimensional (3D) enhanced T₁ high-resolution isotropic volume excitation (eTHRIVE) shoulder MR for variable shoulder pathology such as rotator cuff tear, labral injury and synovial pathology in comparison with two-dimensional enhanced fast spin echo T₁ fat saturation (2D T1 FS) sequences MR.

Methods:

This retrospective study included 86 patients who underwent MRI of the shoulder using eTHRIVE technique. Two radiologists evaluated anatomic identification of the supraspinatus, glenoid labrum and acromioclavicular joint (AC joint) on routine MRI sequences (2D T1 FS) and compared them with the reformatted eTHRIVE images. Subjective scoring of the images was performed with a four-point scale that rated the degree of discrimination of the shape of the supraspinatus, glenoid labrum and AC joint. The diagnostic accuracy of eTHRIVE compared with routine MR images was evaluated in terms of rotator cuff pathology, labral pathology and synovial pathology.

Results:

Anatomic identification scores of the supraspinatus tendon and labrum were significantly lower for eTHRIVE than for 2D T1 FS. There were no significant differences between eTHRIVE and 2D T1 FS in anatomic identification of the AC joint. There were no significant differences between eTHRIVE and 2D T1 FS in diagnosing the three disease categories.

Conclusion:

eTHRIVE had comparable diagnostic accuracy to 2D T1 FS imaging in the evaluation of rotator cuff tears, labral injury and synovial pathology, but anatomic identification was inferior to that of 2D T1 FS.

Advances in knowledge:

The accuracy of 3D eTHRIVE imaging is comparable to that of 2D T1 FS for the diagnosis of rotator cuff tears, labral injury and synovial pathology.     

Tissue-engineered cartilage using fibrin/hyaluronan composite gel and its in vivo implantation

The importance of scaffold biomaterials has been emphasized for in vitro culture of tissue-engineered cartilage in a three-dimensional (3D) environment. In this study, we examined the feasibility of fibrin glue, mixed with hyaluronic acid (HA) as a composite scaffold. Fibrin glue has been a useful cell delivery matrix for cartilage tissue engineering and HA is a key component of normal articular cartilage. Our hypothesis is that compared to fibrin itself, a fibrin/HA composite can have significantly enhanced properties, due mainly to the added benefits of HA in the matrix. Pieces of cartilage were isolated from rabbit knees and the chondrocytes were harvested through enzymatic digestion. Both fibrin and fibrin/HA composite were prepared and subsequently implanted in nude mice (n = 9, each group) for 1, 2, and 4 weeks, respectively. The retrieved specimens were then analyzed and the results were compared. Cartilage-like tissue formation was detected earlier with fibrin/HA specimens. They produced significantly higher amounts of the extracellular matrix (ECM) molecules, GAG, and collagen at each time point than those in fibrin. Interestingly, the fibrin/HA composite was also competent in maintaining its initial size. Histology--Safranin O/fast green and Alcian blue--of the retrieved specimens found more intense, uniform staining in the fibrin/HA composites. Analysis of the gene expression of the ECM molecules also confirmed the benefits of the composite with added HA in the maintenance of phenotypic stability. The present study suggests that fibrin/HA composite may serve as a dependable cell delivery vehicle as well as a structural basis for tissue-engineered cartilage.     

Surgical outcomes of lateral approach for jugular foramen schwannoma: postoperative facial nerve and lower cranial nerve functions

The lateral surgical approach to jugular foramen schwannomas (JFS) may result in complications such as temporary facial nerve palsy (FNP) and hearing loss due to the complicated anatomical location. Ten patients with JFS surgically treated by variable methods of lateral approach were retrospectively reviewed with emphasis on surgical methods, postoperative FNP, and lower cranial nerve status. Gross total removal of the tumors was achieved in eight patients. Facial nerves were rerouted at the first genu (1G) in six patients and at the second genu in four patients. FNP of House–Brackmann (HB) grade III or worse developed immediately postoperatively in six patients regardless of the extent of rerouting. The FNP of HB grade III persisted for more than a year in one patient managed with rerouting at 1G. Among the lower cranial nerves, the vagus nerve was most frequently paralyzed preoperatively and lower cranial nerve palsies were newly developed in two patients. The methods of the surgical approach to JFS can be modified depending on the size and location of tumors to reduce injury of the facial nerve and loss of hearing. Careful manipulation and caution are also required for short facial nerve rerouting as well as for long rerouting to avoid immediately postoperative FNP.     

The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women

Summary  Few studies have evaluated the effects of homocysteine and methylenetetrahydrofolate reductase (MTHFR) genotype on age-related bone loss. In our 5-year cohort study with 1,213 women aged 70–85 years, high homocysteine is associated with greater hip bone loss but not fracture risk. The effect of MTHFR genotype on bone density and fracture is weak. Introduction  Previous studies on the effects of homocysteine and MTHFR genotype on bone mineral density (BMD) and osteoporotic fracture risk have shown inconsistent results. Few studies have evaluated their effects on age-related bone loss. We evaluated the effects of homocysteine and MTHFR genotype variation on hip BMD and fracture risk over 5 years in a cohort of 1,213 community-dwelling women aged 70–85 years. Methods  Nutritional intake and prevalent fracture status were assessed at baseline, plasma homocysteine was measured at year 1, and hip dual-energy X-ray absorptiometry (DXA) BMD was measured at years 1 and 5. Clinical incident osteoporotic fractures confirmed by radiographic report were collected throughout the study and the MTHFR gene C677T and A1298C polymorphisms genotyped. Data were analyzed using analysis of covariance and Cox proportional hazard regression. Results  The highest tertile of homocysteine was associated with a greater hip BMD loss over 4 years (−2.8%) compared to the middle (−1.6%) and lowest tertiles (−1.2%) (P < 0.001). This effect remained after adjustment for covariates. There was no effect of homocysteine on fracture prevalence or incidence. MTHFR gene variation was only weakly related to one of the bone outcome measures. Conclusion  In this study population, high homocysteine is associated with greater hip bone loss but not fracture risk.