Immediate versus delayed prostatectomy and the fate of patients who progress to a higher risk disease on active surveillance. / Prostatectomía inmediata versus demorada en pacientes que progresan a una enfermedad de mayor riesgo en vigilancia activa.

INTRODUCTION: Oncological outcomes of radical prostatectomy (RP) in patients progressing on active surveillance (AS) are debated. We compared outcomes of AS eligible patients undergoing RP immediately after diagnosis with those doing so after delay or disease progression on AS. METHODS: Between 2000 and 2014, 961 patients were AS eligible as per EAU criteria. RP within 6 months of diagnosis (IRP) or beyond (DRP), RP without AS (DRPa) and AS patients progressing to RP (DRPb) were compared. Baseline PSA, clinical and biopsy characteristics were noted. Oncological outcomes included adverse pathology in RP specimen and biochemical recurrence (BCR). Matched pair analysis was done between DRPb and GS7 patients undergoing immediate RP (GS7IRP). RESULTS: IRP, DRP, DRPa and DRPb had 820 (85%), 141 (15%), 118 (12.24%) and 23 (2.7%) patients respectively. IRP, DRPa and DRPb underwent RP at a median of 3, 9 and 19 months after diagnosis respectively. Baseline characteristics were comparable. DRP vs. IRP had earlier median time (31 vs. 43 months; p<.001) and higher rate of progression to BCR (7.6 vs. 3.9%;p=.045). DRPb showed higher BCR (19 vs. 5%;p=.021) with earlier median time to BCR, compared to IRP and DRPa (p=.038). There was no difference in adverse pathology and BCR rates, but time to BCR was significantly lesser in DRPb (49 vs. 6 months;p<.001), compared to GS7IRP. CONCLUSIONS: Patients progressing on AS had worst oncological outcomes. RP for GS7 progression and matched pair of GS7 patients had similar outcomes. Worse oncological outcomes in AS progressors cannot be explained by a mere delay in RP.

Oncological outcomes and pathological characteristics of cT1 upstaging to pT3a renal cell carcinoma compared with de novo pT3a tumors. / Resultados oncológicos y características patológicas de la sobrestadificación de cT1 a carcinoma de células renales pT3a en comparación con los tumores pT3a de novo.

INTRODUCTION: The significance of upstaging of cT1 renal tumors to pT3a is not clear. We evaluate the incidence of upstaging, identify predictors and analyze oncological outcomes of these patients versus those who did not upstage. We also compared the oncological outcomes of cT1 upstaging to pT3a with de novo pT3a renal tumors. METHODS: From a database of 1021 renal tumors with complete available follow-up data, 517 patients had cT1. Patients upstaging to pT3a were compared to those who did not. Baseline clinical, perioperative, histopathologic features and oncological outcomes were analysed. RESULTS: Out of 517 cT1 patients, 105 (20.3%) upstaged to pT3a and 412 (79.7%) did not. Proportion of patients in each group undergoing partial and radical nephrectomy, postoperative tumor size, histology, margin status and lymph node involvement were similar. Among upstaged, 9 patients (8.6%) developed first recurrence as compared to only 3 (0.7%) in those not upstaging (P <0.001). The median time to recurrence (57 vs. 107 months; P <0.001) was lesser in de novo pT3a renal tumors. CONCLUSIONS: Pathological upstaging from cT1 to pT3a and necrosis on histopathology were associated with recurrence. Advanced age, smoking, necrosis on histopathology, clear cell histology and higher Fuhrman grades contributed to pathological upstaging of cT1 tumors. De novo pT3a RCC had worse survival when compared to cT1 patients upstaging to pT3a RCC.

Patient selection for prostate focal therapy in the era of active surveillance: an International Delphi Consensus Project.

BACKGROUND: Whole-gland extirpation or irradiation is considered the gold standard for curative oncological treatment for localized prostate cancer, but is often associated with sexual and urinary impairment that adversely affects quality of life. This has led to increased interest in developing therapies with effective cancer control but less morbidity. We aimed to provide details of physician consensus on patient selection for prostate focal therapy (FT) in the era of contemporary prostate cancer management. METHODS: We undertook a four-stage Delphi consensus project among a panel of 47 international experts in prostate FT. Data on three main domains (role of biopsy/imaging, disease and patient factors) were collected in three iterative rounds of online questionnaires and feedback. Consensus was defined as agreement in ⩾80% of physicians. Finally, an in-person meeting was attended by a core group of 16 experts to review the data and formulate the consensus statement. RESULTS: Consensus was obtained in 16 of 18 subdomains. Multiparametric magnetic resonance imaging (mpMRI) is a standard imaging tool for patient selection for FT. In the presence of an mpMRI-suspicious lesion, histological confirmation is necessary prior to FT. In addition, systematic biopsy remains necessary to assess mpMRI-negative areas. However, adequate criteria for systematic biopsy remains indeterminate. FT can be recommended in D'Amico low-/intermediate-risk cancer including Gleason 4+3. Gleason 3+4 cancer, where localized, discrete and of favorable size represents the ideal case for FT. Tumor foci <1.5 ml on mpMRI or <20% of the prostate are suitable for FT, or up to 3 ml or 25% if localized to one hemi-gland. Gleason 3+3 at one core 1mm is acceptable in the untreated area. Preservation of sexual function is an important goal, but lack of erectile function should not exclude a patient from FT. CONCLUSIONS: This consensus provides a contemporary insight into expert opinion of patient selection for FT of clinically localized prostate cancer.

Higher number of transrectal ultrasound guided prostate biopsy cores is associated with higher blood loss and perioperative complications in robot assisted radical prostatectomy. / Un mayor número de cilindros de biopsia transrectal de próstata guiada por ultrasonido se asocia con una mayor pérdida de sangre y complicaciones perioperatorias en la prostatectomía radical asistida por robot.

INTRODUCTION: The local inflammatory process after prostate biopsies can have a negative impact on functional outcomes of radical prostatectomy. There is no evidence in literature demonstrating its impact on radical prostatectomy. OBJECTIVES: To evaluate the impact of the number of TRUS core biopsies in the surgical morbidity and rate of positive margin on robot assisted radical prostatectomy (RARP). MATERIAL AND METHODS: A prospectively maintained database of 2,054 RARPs in a single institution. Patients were further grouped into 2 groups based on the number of TRUS biopsy cores (G1≤12 cores; G2>12 cores). Multivariable logistic regression model was applied to analyze the impact of number of cores on complications. RESULTS: A total number of 1,042 patients in the group 1 (≤12 cores) and 1,012 patients in the group 2 (>12 cores) were included. The rate of perioperative complications increased with higher number of biopsies (G1 6.4 vs. G2 8.5%; P=.03), but high grade complication (Clavien 3-4) were similar (G1 1.4 vs. G2 2.2%; P=.16). Positive surgical margin rates were similar in both groups (G1 11.8 vs. 9.98%; P=.2). At the multivariable logistic regression analysis shown that G2 had a 39% (OR 0.645) higher rate to experience perioperative complications during RARP. CONCLUSION: Higher number of TRUS biopsy cores (>12) is associated to higher blood loss and perioperative complications during RARP. Careful preoperative evaluation for those patients underwent multiple biopsies or saturation protocols is mandatory. Application of longer intervals (>6 weeks) between biopsy and surgery may be advisable to minimize potential risks of surgical complications in patients may benefit from RARP. Further studies are still necessary to confirm these results.

Infantile (Preductal) Coarctation of Aorta Presenting as Cerebellar Infarct - A Rare Presentation.

Coarctation of aorta is a common congenital heart defect. The diagnosis may be missed unless a highindex of suspicion is maintained, and is often delayed until the patient develops congestive heart failure (CHF), (common in infants) or hypertension (common in older children). It seldom goes undiagnosed till adulthood and frequently leads to complications as a result of long-standing high blood pressure. Intracranial haemorrhage, premature coronary artery disease, aortic aneurysms and rupture have all been reported. But it is rare to see a patient with preductal (infantile) coarctation survive childhood and presents with an infarct in adulthood. We herein present a case report of a young woman who came with vomiting and giddiness and was diagnosed as a case of cerebellar infarct due to a concealed preductal (infantile) coarctation of aorta.

High intensity focused ultrasound with Focal-One® device: Prostate-specific antigen impact and morbidity evaluation during the initial experience. / Ultrasonido focalizado de alta intensidad con el dispositivo Focal-One®: impacto sobre el antígeno prostático específico y evaluación de la morbilidad durante la experiencia inicial.

OBJECTIVE: We report our initial experience in the treatment of prostate cancer (PCa) with high-intensity focused ultrasound (HIFU) using the Focal-One® device. MATERIAL AND METHODS: Retrospective review of the prospectively populated database. Between June 2014 to October 2015, 85 patients underwent HIFU (focal/whole-gland) treatment for localized PCa. Preoperative cancer localization was done with multiparametric magnetic resonance imaging (mpMRI) and transperineal mapping biopsies. Treatment was carried out using the Focal-One® device under general anesthesia. Oncological follow-up: PSA measurement and control biopsy with mpMRI according to protocol. Questionnaire-based functional outcome assessment was done. Complications were reported using Clavien classification. RESULTS: The median PSA was 7.79ng/ml (IQR 6.32-9.16), with a median prostate volume of 38cc (IQR: 33-49.75). Focal and whole-gland therapy was performed in 64 and 21 patients respectively. Ten patients received salvage HIFU. Complications were encountered in 15% of cases, all Clavien 2 graded. Mean hospital stay was 1.8 days (0-7) and bladder catheter was removed on day 2 (1-6). Mean percentage reduction of PSA was 54%. Median follow-up was 3 months (IQR: 2-8). Functional outcomes: All patients were continents at 3 months and potency was maintained in 83% of the preoperatively potent. CONCLUSIONS: Focal-One® HIFU treatment appears to be a safe procedure with few complications. Functional outcomes proved no urinary incontinence and sexual function were maintained in 83%.

Clinical performance of transperineal template guided mapping biopsy for therapeutic decision making in low risk prostate cancer. / Rendimiento clínico de biopsia de mapeo guiada por plantilla transperineal para la toma de decisiones terapéuticas en el cáncer de próstata de bajo riesgo.

OBJECTIVES: To evaluate the role of Transperineal Template guided Mapping Biopsy (TTMB) in determining the management strategy in patients with low risk prostate cancer (PCa). METHODS: We retroscpectively evaluated 169 patients who underwent TTMB at our institution from February 2008 to June 2011. Ninety eight of them harbored indolent PCa defined as: Prostate Specific Antigen<10ng/ml, Gleason score 6 or less, clinical stage T2a or less, unilateral disease and a maximum of one third positive cores at first biopsy and<50% of the core involved. TTMB results were analyzed for Gleason score upgrading and upstaging as compared to initial TransRectal UltraSound (TRUS) biopsies and its influence on the change in the treatment decisions. RESULTS: TTMB detected cancer in 64 (65%) patients. The upgrade, upstage and both were noted in 33% (n=21), 12% (n=8) and 7% (n=5) respectively of the detected cancers. The disease characteristics was similar to initial TRUS in 30 (48%) patients and TTMB was negative in 34 (35%) patients. Prostate volume was significantly smaller in patients with upgrade and/or upstage noted at TTMB (45.4 vs 37.9; P=.03). TTMB results influenced 73.5% of upgraded and/or upstaged patients to receive radical treatment while 81% of the patients with unmodified stage and/or grade continued active surveillance or focal therapy. CONCLUSIONS: In patients with low risk PCa diagnosed by TRUS, subsequent TTMB demonstrated cancer upgrade and/or upstage in about one-third of the patients and resulted in eventual change in treatment decision.

High intensity focused ultrasound for Focal Therapy of prostate cancer.

High Intensity Focused Ultrasound (HIFU) is a heat based energy source used for tissue ablation. HIFU has several clinical applications and prostate cancer ablation is one of the uses that have been explored for more than a decade. Focal therapy is an alternative treatment option for selected patients with low/intermediate PCa, that is based on complete ablation of tumor within the prostate with preservation of normal parenchyma and better preservation of Genitourinary functions. In spite of PCa being predominantly a multi-centric disease, it is postulated that a specific dominant (large volume) 'index lesion' dictates the biological behavior of the cancer and subsequent lethality of the disease. The use of HIFU for focal ablation of PCa, have demonstrated satisfactory cancer control with fewer morbidity and better preservation of continence and erection. The aim of this article is to present the readers with a brief review of the principles, devices available for clinical uses, published clinical experience and future directions and research opportunities in focal HIFU ablation of prostate cancer.

[Localized prostate cancer Focal Therapy: "A la carte" Model]. / Tratamiento Focal del cáncer de próstata localizado: Modelo "À la carte".

Focal therapy has settled as an alternative to radical treatment in selected cases of localized prostate cancer. The selection of patients who are candidates for focal therapy is based on imaging diagnosis relying on multiparametric MRI and image fusion techniques. Thanks to the oncological results and safety profiles of initial series, various energy sources have been developed over the last years. The availability of multiple types of energy sources for focal therapy, commits us to evaluate what type of energy would be the optimal depending on patient's profile and type of lesion. A unique energy for focal therapy would be ideal, but facing the research of the various types of energy we must identify which one is recommended for each lesion. With the experience of our center in different approaches of focal therapy we propose the "A LA CARTE" MODEL based on localization of the lesion. We present the criteria the "a la carte" model is based on, supported by the published evidence on the use of different ablative therapies for the treatment of localized prostate cancer. Lesion localization, technical characteristics of each type of energy, patient's profile and secondary effects must be considered in every choice of focal therapy.

Evolution of prostate biopsy techniques. Looking back on a meaningful journey. / Evolución de las técnicas de biopsia prostática. Mirando hacia atrás en un viaje significativo.

BACKGROUND: The technique of prostate biopsy has evolved a long way since its inception to being a safe diagnostic procedure. The principles of the biopsy technique continue to improvise with the knowledge about prostate cancer and availability of newer treatment options like active surveillance and focal therapy. Currently, we depend on accurate cancer information from the biopsy more than ever for deciding the ideal treatment option. AIM: The aim of this review is to present the major milestones in prostate biopsy technique evolutions and its impact on the prostate cancer management. ACQUISITION OF EVIDENCE: We performed a detailed non-systematic literature review to present the historical facts on the transformations in prostate biopsy techniques and also the direction of present research to improve accurate cancer detection. SUMMARY OF EVIDENCE: There is a clear change in trend in biopsy technique before and after the introduction of transrectal ultrasound and prostate specific antigen. In the earlier era, the biopsies were aimed at palpable nodules and obtaining adequate prostatic tissue for diagnosis while the later era has moved towards detection of non-palpable and early prostate cancer. Recently, there is an increasing trend towards image guided targeted biopsies to extract maximum cancer information from minimum biopsy cores. CONCLUSION: Prostate biopsy techniques have seen major changes since its inception and have a major impact on prostate cancer management. There is a great potential for research which can further support the newer treatment options like focal therapy.

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy.

INTRODUCTION: The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS: We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS: The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION: Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

Robotics in urological surgery: evolution, current status and future perspectives.

CONTEXT: Robotic surgery is rapidly evolving and has become an essential part of surgical practice in several parts of the world. Robotic technology will expand globally and most of the surgeons around the world will have access to surgical robots in the future. It is essential that we are updated about the outcomes of robot assisted surgeries which will allow everyone to develop an unbiased opinion on the clinical utility of this innovation. OBJECTIVE: In this review we aim to present the evolution, objective evaluation of clinical outcomes and future perspectives of robot assisted urologic surgeries. ACQUISITION OF EVIDENCE: A systematic literature review of clinical outcomes of robotic urological surgeries was made in the PUBMED. Randomized control trials, cohort studies and review articles were included. Moreover, a detailed search in the web based search engine was made to acquire information on evolution and evolving technologies in robotics. SYNTHESIS OF EVIDENCE: The present evidence suggests that the clinical outcomes of the robot assisted urologic surgeries are comparable to the conventional open surgical and laparoscopic results and are associated with fewer complications. However, long term results are not available for all the common robotic urologic surgeries. There are plenty of novel developments in robotics to be available for clinical use in the future. CONCLUSION: Robotic urologic surgery will continue to evolve in the future. We should continue to critically analyze whether the advances in technology and the higher cost eventually translates to improved overall surgical performance and outcomes.

Prospective Study of Posterior Lumbar Interbody Fusion With Either Interbody Graft or Interbody Cage in the Treatment of Degenerative Spondylolisthesis.

STUDY DESIGN: A prospective study of 2 different fusion techniques for the treatment of single-level degenerative spondylolisthesis. OBJECTIVE: To determine whether the addition of an intervertebral cage improves the clinical outcome and fusion rate of patients undergoing posterior lumbar interbody fusion (PLIF) after decompression for degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: The surgical approach that should be used for degenerative spondylolisthesis is a controversial issue. Decompression and PLIF with an interbody cage is widely used. Theoretical advantages in favor of PLIF include anterior column support, indirect foraminal decompression, restoration of lordosis, and reduction of the slip via ligamentotaxis. Despite numerous publications, the scientific support for the PLIF method is, however, weak. MATERIALS AND METHODS: A prospective study was carried out including 59 patients with degenerative spondylolisthesis. Average age of patients was 66 years: 34 males and 25 females. Patients were divided into 2 treatment groups: group 1-32 patients with PLIF with interbody graft and group 2-27 patients with PLIF with cage. Minimum 2-year follow-up. Outcomes were assessed by measuring preoperative and postoperative lordotic angles. SF-12 physical and mental health scores were recorded along with visual analogue scores for pain. Complications were also recorded. RESULTS: No significant difference in the postoperative lordotic angles was achieved between the 2 techniques. Nonsignificant difference in the clinical outcomes between both the techniques. CONCLUSIONS: We have found the use of a cage to achieve lumbar interbody fusion in the treatment of degenerative lumbar spondylolisthesis does not confer any significant advantages in terms of restoration of lumbar lordosis, improvement in clinical symptoms, or relief of pain postoperatively.

The role of proteases and inflammatory molecules in triggering neovascular age-related macular degeneration: basic science to clinical relevance.

Age-related macular degeneration (AMD) causes severe vision impairment in aged individuals. The health impact and cost of the disease will dramatically increase over the years, with the increase in the aging population. Currently, antivascular endothelial growth factor agents are routinely used for managing late-stage AMD, and recent data have shown that up to 15%-33% of patients do not respond to this treatment. Henceforth, there is a need to develop better treatment options. One avenue is to investigate the role proteases and inflammatory molecules might have in regulating and being regulated by vascular endothelial growth factor. Moreover, emerging data indicate that proteases and inflammatory molecules might be critical in the development and progression of AMD. This article reviews recent literature that investigates proteases and inflammatory molecules involved in the development of AMD. Gaining insights into the proteolytic and inflammatory pathways associated with the pathophysiology of AMD could enable the development of additional or alternative drug strategies for the treatment of AMD.

Preliminary identification of differentially expressed tear proteins in keratoconus.

PURPOSE: To examine the proteins differentially expressed in the tear film of people with keratoconus and normal subjects. METHODS: Unstimulated tears from people with keratoconus (KC) and controls (C) were collected using a capillary tube. Tear proteins from people with KC and controls were partitioned using a novel in-solution electrophoresis, Microflow 10 (ProteomeSep), and analyzed using linear ion trap quadrupole fourier transform mass spectrometry. Spectral counting was used to quantify the individual tear proteins. RESULTS: Elevated levels of cathepsin B (threefold) were evident in the tears of people with KC. Polymeric immunoglobulin receptor (ninefold), fibrinogen alpha chain (eightfold), cystatin S (twofold), and cystatin SN (twofold) were reduced in tears from people with KC. Keratin type-1 cytoskeletal-14 and keratin type-2 cytoskeletal-5 were present only in the tears of people with KC. CONCLUSIONS: The protein changes in tears, that is, the decrease in protease inhibitors and increase in proteases, found in the present and other previously published studies reflect the pathological events involved in KC corneas. Further investigations into tear proteins may help elucidate the underlying molecular mechanisms of KC, which could result in better treatment options.

Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus.

BACKGROUND: Proteases, protease activity and inflammatory molecules in tears have been found to be relevant in the pathogenesis of keratoconus. We sought to determine the influence of eye rubbing on protease expression, protease activity and concentration of inflammatory molecules in tears. METHODS: Basal tears were collected from normal volunteers before and after 60 seconds of experimental eye rubbing. The total amount of matrix metalloproteinase (MMP)-13 and inflammatory molecules interleukin (IL)-6 and tumour necrosis factor (TNF)-α in the tear samples were measured using specific enzyme-linked immunosorbent assays (ELISA). Tear collagenase activity was investigated using a specific activity assay. RESULTS: The concentrations of MMP-13 (51.9 ± 34.3 versus 63 ± 36.8 pg/ml, p = 0.006), IL-6 (1.24 ± 0.98 versus 2.02 ± 1.52 pg/ml, p = 0.004) and TNF-α (1.16 ± 0.74 versus 1.44 ± 0.66 pg/ml, p = 0.003) were significantly increased in normal subjects after eye rubbing. The experimental eye rub did not alter significantly the collagenase activity (5.02 ± 3 versus 7.50 ± 3.90 fluorescent intensity units, p = 0.14) of tears. CONCLUSION: Eye rubbing for 60 seconds increased the level of tear MMP-13, IL-6 and TNF-α in normal study subjects. This increase in protease, protease activity and inflammatory mediators in tears after eye rubbing may be exacerbated even further during persistent and forceful eye rubbing seen in people with keratoconus and this in turn may contribute to the progression of the disease.

[Bidirectional barbed suture for bladder neck reconstruction, posterior reconstruction and vesicourethral anastomosis during robot assisted radical prostatectomy]. / Sutura barbada bidireccional para la reconstrucción del cuello vesical, la reconstrucción posterior y la anastomosis vesicouretral durante la prostatectomía radical asistida por robot.

BACKGROUND: The urethrovesical anastomosis is a particular challenging step of robot assisted radical prostatectomy (RARP). Failure to achieve a watertight anastomosis is associated with postoperative urinary leak and its consequences, which include paralytic ileus, prolonged catheterization, urinary peritonitis and possibly re-intervention. The bidirectional barbed suture is a new technology that may lead to improve the quality of the urethrovesical anastomosis. OBJECTIVE: To present our surgical technique of urethrovesical anastomosis, bladder neck reconstruction and posterior reconstruction, using a bidirectional barbed suture. MATERIAL AND METHODS: The bladder neck reconstruction, posterior reconstruction and vesicourethral anastomosis were performed using a 2-0 synthetic absorbable bidirectional monofilament barbed suture RESULTS: All cases were finished successfully without major complication or conversion to laparoscopic or open surgery. CONCLUSION: The authors successfully modified their RARP technique to take advantage of the properties of the bidirectional barbed suture. Comparative studies that evaluate objective outcomes such as leakage rates and operative time are needed to definitely establish the benefits of this device in comparison to the traditional absorbable monofilament.

[Robotic surgery: history and teaching impact]. / Cirugía robótica: Historia e impacto en la enseñanza.

CONTEXT: The purpose of this article is to review the history of robotic surgery, its impact on teaching as well as a description of historical and current robots used in the medical arena. SUMMARY OF EVIDENCE: Although the history of robots dates back to 2000 years or more, the last two decades have seen an outstanding revolution in medicine, due to all the changes that robotic surgery has made in the way of performing, teaching and practicing surgery. CONCLUSIONS: Robotic surgery has evolved into a complete and self-contained field, with enormous potential for future development. The results to date have shown that this technology is capable of providing good outcomes and quality care for patients.

Repair of spondylolysis using compression with a modular link and screws.

We describe the results of a prospective case series of patients with spondylolysis, evaluating a technique of direct stabilisation of the pars interarticularis with a construct that consists of a pair of pedicle screws connected by a U-shaped modular link passing beneath the spinous process. Tightening the link to the screws compresses bone graft in the defect in the pars, providing rigid intrasegmental fixation. We have carried out this procedure on 20 patients aged between nine and 21 years with a defect of the pars at L5, confirmed on CT. The mean age of the patients was 13.9 years (9 to 21). They had a grade I or less spondylolisthesis and no evidence of intervertebral degeneration on MRI. The mean follow-up was four years (2.3 to 7.3). The patients were assessed by the Oswestry Disability Index (ODI) and a visual analogue scale (VAS). At the latest follow-up, 18 patients had an excellent clinical outcome, with a significant (p < 0.001) improvement in their ODI and VAS scores. The mean ODI score at final follow-up was 8%. Assessment of the defect by CT showed a rate of union of 80%. There were no complications involving the internal fixation. The strength of the construct removes the need for post-operative immobilisation.

Are proteinases the reason for keratoconus?

PURPOSE: Keratoconus is a degenerating disease of the eye that results in an irregularly-shaped cornea. The etiology of the disease is unknown and the prognosis is difficult due to the variability in outcome. Keratoconus has been associated with eye rubbing, atopy, contact lens wear, as well as genetic conditions, such as Down's syndrome, Ehlers-Danlos syndrome, and Marfan's syndrome. Thinning of the cornea in keratoconus has been well studied and is documented to occur as a result of degradation of corneal collagen. The reason for this tissue degradation is unknown but has been hypothesized to be linked with proteases. METHODS: This study used a literature search to review the role of proteases and inflammatory molecules in the aetiology of keratoconus. RESULTS: Early studies demonstrated elevated levels of collagenolytic and gelatinolytic activities in laboratory cultures of keratoconic corneas. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteins that include collagenases and gelatinases. MMPs levels are altered in keratoconus corneas compared to normal corneas and the level of tissue inhibitor of metalloproteinases-1 (TIMP-1) is decreased in keratoconic corneas. Recent studies have demonstrated the involvement of Cathepsin B, G, and K in keratoconus. Although thought to be a non-inflammatory disease, inflammatory molecules, such as interleukins and tumor necrosis factor have been shown to be elevated in keratoconus, and these inflammatory molecules may mediate production and activation of proteases. CONCLUSIONS: Proteases may be implicated in keratoconus. An in-depth investigation of these proteases may help in better understanding the course of the disease.