Findings in 1,123 Men with Preoperative 68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography and Multiparametric Magnetic Resonance Imaging Compared to Totally Embedded Radical Prostatectomy Histopathology: Implications for the Diagnosis and Management of Prostate Cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) fails to identify some men with significant prostate cancer. Prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT) is recommended for staging of prostate cancer, but its additional benefit above mpMRI alone in local evaluation for prostate cancer is unclear. The study aim was to evaluate the ability of mpMRI and PSMA PET/CT individually and in combination, to predict tumor location and Gleason score ≥3+4 on robot-assisted laparoscopic radical prostatectomy (RALP) histology. MATERIALS AND METHODS: We retrospectively reviewed 1,123 men with a preoperative mpMRI and 68Ga-PSMA PET/CT prior to a RALP. Tumor locations were collected from both imaging modalities and compared to totally embedded prostate histology. Lowest apparent diffusion coefficient value on mpMRI and the highest maximum standardized uptake value (SUVmax) on 68Ga-PSMA PET/CT were collected on the index lesions to perform analysis on detection rates. RESULTS: Median prostate specific antigen was 6. Median Gleason score on biopsy and RALP histology was 4+3. The index lesion and multifocal tumor detection were similar between mpMRI and 68Ga-PSMA PET/CT (p=0.10; p=0.11). When combining mpMRI and 68Ga-PSMA PET/CT, index Gleason score ≥3+4 cancer at RALP was identified in 92%. Only 10% of patients with Gleason score ≤3+4 on biopsy with an SUVmax <5 were upgraded to ≥4+3 on RALP histology, compared to 90% if the SUVmax was >11. CONCLUSIONS: The addition of a diagnostic 68Ga-PSMA PET/CT to mpMRI can improve the detection of significant prostate cancer and improve the ability to identify men suitable for active surveillance.

A national UK audit of suprapubic catheter insertion practice and rate of bowel injury with comparison to a systematic review and meta-analysis of available research.

OBJECTIVES: Limited data exist on the risks of complications associated with a suprapubic catheter (SPC) insertion. Bowel injury (BI) is a well-recognized albeit uncommon complication. Guidelines on the insertion of SPC have been developed by the British Association of Urological Surgeons, but there remains little evidence regarding the incidence of this complication. This study uses contemporary UK data to assess the incidence of SPC insertion and the rate of BI and compares to a meta-analysis of available papers. METHODS: National Hospital Episodes Statistics data were searched on all SPC insertions over an 18-month period for operating procedure codes, Code M38.2 (cystostomy and insertion of a suprapubic tube into bladder). Patients age, 30-day readmission rates, 30-day mortality rate, and catheter specific complication rate were collected. To estimate the BI rate, we searched patients who had undergone any laparotomy or bowel operation within 30 days of SPC insertion. Trusts were contacted directly and directed to ascertain whether there was SPC-related BI. PubMed search to identify papers reporting on SPC related BI was performed for meta-analysis RESULTS: 11 473 SPC insertions took place in the UK in this time period. One hundred forty-one cases had laparotomy within 30 days. Responses from 114 of these cases reported one BI related to SPC insertion. Meta-analysis showed an overall BI rate of 11/1490 (0.7%). CONCLUSIONS: This is the largest dataset reported on SPC insertions showing a lower than previously reported rate of BI. We recommend clinicians use a risk of BI of less than 0.25% when counseling low-risk patients.

Usage of unicompartmental knee arthroplasty.

Unicompartmental knee arthroplasty (UKA) has numerous advantages over total knee arthroplasty (TKA) and one disadvantage, the higher revision rate. The best way to minimize the revision rate is for surgeons to use UKA for at least 20% of their knee arthroplasties. To achieve this, they need to learn and apply the appropriate indications and techniques. This would decrease the revision rate and increase the number of UKAs which were implanted, which would save money and patients would benefit from improved outcomes over their lifetime. Cite this article: Bone Joint J 2018;100-B:432-5.

Cytoplasmic PML promotes TGF-ß-associated epithelial-mesenchymal transition and invasion in prostate cancer.

Epithelial-mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-ß signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-ß signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-ß canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-ß signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit.

Treatment adherence in cognitive processing therapy for combat-related PTSD with history of mild TBI.

OBJECTIVE: This retrospective study examined treatment adherence in Cognitive Processing Therapy (CPT) for combat-related posttraumatic stress disorder (PTSD) in Veterans of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) with and without history of mild traumatic brain injury (mTBI). METHOD: Medical record review of consecutive referrals to an outpatient PTSD clinic identified veterans diagnosed with combat-related PTSD who began treatment with CPT. The sample (N = 136) was grouped according to positive (n = 44) and negative (n = 92) mTBI history. Groups were compared in terms of presenting symptoms and treatment adherence. RESULTS: The groups were not different on a pretreatment measure of depression, but self-reported and clinician-rated PTSD symptoms were higher in veterans with history of mTBI. The treatment completion rate was greater than 61% in both groups. The number of sessions attended averaged 9.6 for the PTSD group and 7.9 for the mTBI/PTSD group (p = .05). IMPLICATIONS: Given the lack of marked group differences in treatment adherence, these initial findings suggest that standard CPT for PTSD may be a tolerable treatment for OEF/OIF veterans with a history of PTSD and mTBI as well as veterans with PTSD alone.

Exploring the efficacy of a residential treatment program incorporating cognitive processing therapy-cognitive for veterans with PTSD and traumatic brain injury.

As the numbers of military personnel participating in the wars in Afghanistan and Iraq continue to grow, the percentage of individuals who return with both a traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) also increases. Although there appears to be significant overlap in the symptoms resulting from PTSD and TBI, the best course of treatment remains an area of controversy. The authors present initial findings from a Veterans Administration residential program for comorbid PTSD and TBI. Forty-two participants completed a program comprising psychoeducational groups and cognitive skill building that was augmented with a modification of standard cognitive processing therapy. The results suggest that residential programs that incorporate this form of cognitive therapy can anticipate meaningful participation from patients, and that it may be an effective approach to treat PTSD in individuals with a history of TBI.

The low contact stress patellofemoral replacement: high early failure rate.

The low contact stress patellofemoral replacement consists of a trochlear component and a modular patellar component which has a metal-backed mobile polyethylene bearing. We present the early results of the use of this prosthesis for established isolated patellofemoral arthritis in 51 consecutive patellofemoral replacements in 35 patients. The mean follow-up was 25 months (5 to 60). The estimated survival rate at three years was 63% (95% confidence interval 47 to 80) with revision as the endpoint and 46% (95% confidence interval 30 to 63) with revision and ongoing moderate or severe pain as the endpoint. The early results of the use of the low contact stress patellofemoral replacement are disappointing with a high rate of revision. We cannot therefore recommend its use.

Renal vein occlusion as a complication of anterior spinal fusion.

We report a 41-year-old female with inferior renal vein compression following anterior lumbar interbody fixation and fusion. Traumatic vascular injuries are not uncommon with anterior approaches to the spine; however, compressive vascular injuries are not well described. This report serves to raise the awareness that such injuries may occur due to distortion of normal anatomy.

A comparison of low back kinetic estimates obtained through posture matching, rigid link modeling and an EMG-assisted model.

This study examined errors introduced by a posture matching approach (3DMatch) relative to dynamic three-dimensional rigid link and EMG-assisted models. Eighty-eight lifting trials of various combinations of heights (floor, 0.67, 1.2 m), asymmetry (left, right and center) and mass (7.6 and 9.7 kg) were videotaped while spine postures, ground reaction forces, segment orientations and muscle activations were documented and used to estimate joint moments and forces (L5/S1). Posture matching over predicted peak and cumulative extension moment (p < 0.0001 for all variables). There was no difference between peak compression estimates obtained with posture matching or EMG-assisted approaches (p = 0.7987). Posture matching over predicted cumulative (p < 0.0001) compressive loading due to a bias in standing, however, individualized bias correction eliminated the differences. Therefore, posture matching provides a method to analyze industrial lifting exposures that will predict kinetic values similar to those of more sophisticated models, provided necessary corrections are applied.

The trigeminocardiac reflex in Onyx embolisation of intracranial dural arteriovenous fistula.

We investigated the incidence of the trigeminocardiac reflex (TCR) during ethylene vinyl alcohol copolymer (Onyx Liquid Embolic System, ev3 Neurovascular, Irvine, CA, USA) embolisation of intracranial dural arteriovenous fistulas (DAVFs) and evaluated the post-procedural recovery of these patients. Between June 2006 and July 2009, 21 patients (11 females, 10 males) with a mean age of 61years (range: 25-85years) underwent 28 Onyx embolisations of intracranial DAVFs at our institution. The case histories of these patients were reviewed retrospectively. A TCR occurred in three (10.7%) of the embolisations, with bradycardia lower than 60 beats/minute and a drop in mean arterial blood pressure of 20% or more. The reflex was blunted promptly with intravenous atropine, and follow-up of these patients showed no complications that might have been directly related to it. The TCR may occur during Onyx embolisation of intracranial DAVFs. Recognition of this phenomenon allows for early detection and appropriate intraoperative management.

Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo.

A hurdle facing DNA vaccine development is the ability to generate strong immune responses systemically and at local immune sites. We report a novel systemically administered DNA vaccination strategy using intramuscular codelivery of CCL27 or CCL28, which elicited elevated peripheral IFN-gamma and antigen-specific IgG while driving antigen-specific T-cell secretion of cytokine and antibody production in the gut-associated lymphoid tissue and lung. This strategy resulted in induction of long-lived antibody responses that neutralized influenza A/PR8/34 and protected mice from morbidity and mortality associated with a lethal intranasal viral challenge. This is the first example of the use of CCL27 and CCL28 chemokines as adjuvants to influence a DNA vaccine strategy, suggesting further examination of this approach for manipulation of vaccine-induced immunity impacting both quality and phenotype of responses.

Onyx embolisation of cavernous sinus dural arteriovenous fistula via direct percutaneous transorbital puncture.

The cavernous sinus dural arteriovenous fistulas of three patients were successfully embolised by using Onyx (Onyx Liquid Embolic System, MTI, Irvine, CA, USA) as the sole embolic agent, through direct percutaneous transorbital punctures of the cavernous sinuses. Our early experience suggests that this direct approach, coupled with the unique physical properties of Onyx, is a safe and effective alternative to treat cavernous sinus dural arteriovenous fistulas when the conventional transvenous routes are inaccessible.

Comparative outcomes following endoscopic ureteral detachment and formal bladder cuff excision in open nephroureterectomy for upper urinary tract transitional cell carcinoma.

PURPOSE: The introduction of laparoscopic nephroureterectomy highlights the need for the critical appraisal of approaches to the distal ureter at surgery for upper tract transitional cell carcinoma. We compared differences after endoscopic ureteral detachment and open bladder cuff excision in nephroureterectomy. MATERIALS AND METHODS: A total of 138 patients underwent open nephroureterectomy for upper urinary tract transitional cell carcinoma from 1982 to 2005 with a median followup of 43 months. Of these patients 90 underwent endoscopic ureteral detachment and 48 underwent bladder cuff excision. Demographic, perioperative and oncological outcome data were collected in all cases. Statistical analyses were performed using the Student t test, chi-square and log rank tests, and logistic and Cox regression. RESULTS: Mean operative duration was significantly lower in the endoscopic detachment group than in the bladder cuff group (p <0.01). There were 49 (54.4%) bladder recurrences in the endoscopic detachment group, of which 8 (16.3%) were muscle invasive and 3 (3.3%) developed at the resection site. There were 23 (47.9%) bladder recurrences in the bladder cuff group, of which 3 (13.0%) were muscle invasive and 2 (4.2%) developed at the resection site. All 5 resection site tumors occurred after excision of muscle invasive distal ureteral tumors and 4 of these had positive margins. There were no differences in recurrence-free survival or disease specific survival between the groups. Operation subtype did not predict oncological outcome on univariate or multivariate analysis. CONCLUSIONS: Endoscopic ureteral detachment reduces operative duration and is associated with equivalent oncological outcomes compared with open bladder cuff excision in nephroureterectomy. Caution should be exercised in patients with low ureteral tumors.

Percutaneous radiofrequency ablation of renal tumours: case series of 11 tumours and review of published work.

Detection of renal cell carcinoma (RCC) is increasing with the greater use of cross-sectional imaging and up to two-thirds of RCCs are discovered incidentally in asymptomatic patients. The traditional option of nephrectomy or partial nephrectomy may not always be appropriate. A minimally invasive treatment alternative is radiofrequency ablation (RFA). We retrospectively reviewed the RFA cases for renal tumours at our institution between January 2004 and June 2006. Thirteen RFA treatment sessions were conducted for 11 neoplasms in 11 patients. Mean patient age was 74.4 years (61-88 years). Imaging was carried out after ablation with a mean follow up of 8.0 months (2-26 months). No residual tumour was observed after the first RFA treatment in 82% of patients (nine of 11). Two patients required a second RFA treatment for residual (one) or recurrent tumour (one). RFA is emerging as a useful technique for treatment of small renal tumour. A number of short-term studies reflect this, however, long-term findings are still lacking.

Comparison of scars and resulting hypoaesthesia between the medial parapatellar and midline skin incisions in total knee arthroplasty.

The two most common skin incisions in total knee arthroplasty (TKA) are the medial parapatellar and midline. As the medial parapatellar incision is predominantly parallel to the Langer's lines of the knee, this may give a better cosmetic appearance. The aim of this study was to assess patient satisfaction of the surgical scar and resulting hypoaesthesia following TKA. Two groups of patients who underwent primary TKA were reviewed. Group 1 consisted of 91 patients who underwent primary TKA using a medial parapatellar incision and trivector arthrotomy with a mean follow up of 2.8 years. Group 2 consisted of 76 patients who underwent primary TKA using a midline incision and medial parapatellar arthrotomy with a mean follow up of 2.7 years. The scars were assessed using the validated Manchester Scar Proforma (MSP) and Visual Analogue Scales (VAS). The resulting hypoaesthesia was assessed using VAS. The mean MSP for Group 1 and Group 2 was 11.7 and 11.9 respectively. The mean area of hypoaesthesia for Group 1 and Group 2 was 28.9 cm(2) and 23.8 cm(2) respectively. There was no statistical significance in any of the parameters measured. The mean length of the incision scar was 19.5 cm for Group 1 and 19.4 cm for Group 2. Both produced equal and excellent cosmetic results. Patients in both groups had hypoaesthesia around the knee at 7 years following their TKA. Hypoaesthesia was not found to be of significant concern to patients. This information may be useful when consenting patients for TKA.

Treatment of naming in nonfluent aphasia through manipulation of intention and attention: a phase 1 comparison of two novel treatments.

Twenty-three chronic nonfluent aphasia patients with moderate or severe word-finding impairments and 11 with profound word-finding impairments received two novel picture-naming treatments. The intention treatment initiated picture-naming trials with a complex left-hand movement and was designed to enhance right frontal participation during word retrieval. The attention treatment required patients to view visual stimuli for picture-naming trials in their left hemispace and was designed to enhance right posterior perisylvian participation during word retrieval. Because the intention treatment addressed action mechanisms and nonfluent aphasia reflects difficulty initiating or maintaining action (i.e., language output), it was hypothesized that intention component of the treatment would enhance re-acquisition of picture naming more than the attention component. Patients with moderate and severe word-finding impairment showed gains with both treatments but greater incremental improvement from one treatment phase to the next with the intention than the attention treatment. Thus, the hypothesis that intention component would be a more active constituent than the attention component was confirmed for these patients. Patients with profound word-finding impairment showed some improvement with both treatments but no differential effects for the intention treatment. Almost all patients who showed treatment gains on either treatment also demonstrated generalization from trained to untrained items.

Universal precaution compliance by orthopaedic trauma team members in a major trauma resuscitation scenario.

INTRODUCTION: We determined the compliance rates of orthopaedic trauma team members in applying universal precautions in major trauma resuscitation scenarios and the availability of universal precautions in accident and emergency (A&E) departments throughout England. MATERIALS AND METHODS: A national telephone survey was implemented contacting the first on-call orthopaedic surgeon and A&E departments in hospital trusts accepting major trauma throughout England. A questionnaire was employed to ascertain current practice, experience and availability of universal precautions when managing a major trauma patient. RESULTS: Overall, 112 first on-call orthopaedic surgeons and 99 A&E departments responded. There was good compliance for using gloves (99%) and aprons (86%). There was poor compliance in using eye protectors (21%), face masks (18%), shoe covers (4%) and head caps (4%). Trainees applied universal precautions according to the level of risk they subjectively perceived. All A&E departments had gloves and aprons but the availability of the other universal precautions was less. Of trainees, 76 reported that all universal precautions were not readily available in the A&E department. CONCLUSION: Orthopaedic trauma team members are very compliant in using gloves and aprons, but should be more compliant in using eye protectors. It is questionable whether face masks, head caps and shoe covers need to be used in all trauma scenarios. In general, universal precautions should be more available in the A&E departments. There should be better communication between A&E departments and the trauma team regarding the availability of universal precautions.

Closed suction drains do not increase the blood transfusion rates in patients undergoing total knee arthroplasty.

We aim to determine whether the presence of a drain increases the actual blood transfusion rates in patients undergoing primary total knee arthroplasty (TKA). A retrospective review was performed on two consecutive groups of patients who underwent primary TKA: group 1 including 100 patients who underwent TKA and had one deep closed suction drain; group 2 including 100 patients who underwent TKA and had no drain. Blood transfusions were given post-operatively on the basis of clinical need without a pre-determined haemoglobin trigger factor. Group 1 drained a mean of 692 ml (range 150-1500) of blood in 48 h. The mean fall in haemoglobin at 48 h post-operatively was 3.26 g/dl in group 1 and 3.33 g/dl in group 2. Nine patients in group 1 and seven patients in group 2 required a blood transfusion; this was not statistically significant (P=0.79). Transfusion of primary TKA patients on the basis of clinical need can result in post-operative transfusion rates of 8%. The presence of a drain does not increase the transfusion rates of patients undergoing primary TKA.