Elena Biagioli

Efficacy and Safety of Trabeculectomy vs Nonpenetrating Surgical Procedures: A Systematic Review and Meta-analysis

IMPORTANCE To date, only a few studies have directly compared nonpenetrating surgery (NPS) and trabeculectomy (TE). Therefore, there is no strong evidence as to which surgical technique leads to the best results in terms of ocular hypotensive effect and safety. OBJECTIVE To compare the hypotensive effect and safety of NPS and TE in terms of intraocular pressure (IOP) reduction and incidence of complications. DATA SOURCES The MEDLINE and EMBASE databases were searched for studies potentially eligible in any language published up to March 31, 2013. STUDY SELECTION Systematic review and meta-analysis of comparative studies of 2 or more surgical techniques (1 of which had to be TE), including patients with open-angle glaucoma. DATA EXTRACTION AND SYNTHESIS The considered interventions were TE, deep sclerectomy (DS), viscocanalostomy, and canaloplasty. MAIN OUTCOMES AND MEASURES The primary outcome was the mean between-group difference in the reduction in diurnal IOP from baseline to the 6- or 12-month follow-up evaluation. We also considered the incidence of complications, expressed as relative risk. RESULTS Eighteen articles, accounting for 20 comparisons, were selected for data extraction and analysis. Analysis of the 6-month follow-up data showed that the pooled estimate of the mean between-group difference was -2.15 mm Hg (95% CI, -2.85 to -1.44) in favor of TE. There was no difference between the NPS subgroups. In the subgroup antimetabolite analysis, the addition of mitomycin C to TE and DS decreased the difference in the reduction in IOP (TE and DS without mitomycin C: -2.65 mm Hg [95% CI, -3.90 to -1.39]; TE and DS with mitomycin C: -0.83 mm Hg [95% CI, -2.40 to 0.74]). In the subgroup analysis by implant addition, no significant difference induced by DS with or without drainage devices was detected (test for subgroup differences: χ(2)(1) = 0.24; P = .62). The absolute risk of hypotony, choroidal effusion, cataract, and flat or shallow anterior chamber was higher in the TE group than in the NPS group. CONCLUSIONS AND RELEVANCE Trabeculectomy seems to be the most effective surgical procedure for reducing IOP in patients with open-angle glaucoma. However, as expected, it was associated with a higher incidence of complications when compared with NPS.

Prostaglandin analogs and timolol-fixed versus unfixed combinations or monotherapy for open-angle glaucoma: A systematic review and meta-analysis

PURPOSE To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) administered in combination with β-blockers. METHODS We searched the Medline and Embase databases for randomized trials comparing topical therapies with PGAs and timolol administered as monotherapy (Mt), or in fixed (FC) or unfixed combinations (UC) to patients with glaucoma or ocular hypertension. The efficacy endpoint was the mean difference (MeD) in the reduction in IOP from baseline; the tolerability endpoint was the incidence of hyperemia. RESULTS The 18 eligible trials involved 23 comparisons of FC versus Mt, and 5 of FC versus UC. The FCs were less efficacious than UCs (MeD: 0.69, 95% CI: 0.29 to 1.08). In comparison with timolol Mt, the latanoprost/timolol FC led to a greater IOP reduction (MeD: -2.74, 95% CI: -3.24 to -2.23) than the bimatoprost/timolol FC (MeD: -1.49, 95% CI: -1.86 to -1.12) or the travoprost/timolol FC (MeD: -1.93, 95%CI: -2.98 to -0.88). The FCs led to a lower hyperemia risk than UCs [relative risk (RR): 0.70, 95% CI: 0.43 to 1.14] and PGA Mt (RR: 0.61, 95% CI: 0.53 to 0.70). CONCLUSIONS FCs are more efficacious than their individual components, but less efficacious than their respective UCs. FCs lead to a lower hyperemia risk than UCs and their respective PGA Mts.

Long-term clinical benefits of neoadjuvant chemotherapy in women with locally advanced cervical cancer: Validity of pathological response as surrogate endpoint of survival

Objective Neoadjuvant chemotherapy (NACT) is a valid treatment option for women with locally advanced cervical cancer (LACC). This study aims to evaluate the impact of sociodemographic factors, clinical factors, and NACT regimens on survival endpoints. The role of pathological response to NACT as a surrogate endpoint of survival was also assessed. Materials and Methods Retrospective analysis of consecutive sample data from women with LACC (stages Ib2-IVa) who underwent NACT followed by radical surgery was performed. Response was classified as optimal response (including complete response and optimal partial response), suboptimal partial response, stable disease, and progressive disease. Results Four hundred forty-six women who had undergone surgery from 1992 to 2011 were analyzed. The overall optimal response was 35.4%. At a median follow-up of 12.7 years, 165 women (37.0%) experienced recurrence or died. Increase in patient age at surgery, International Federation of Gynecology and Obstetrics stage III/IV versus stage Ib2, and lymph-node positivity versus negativity seemed to impact negatively on survival, whereas neoadjuvant platinum-Taxol–containing regimens (compared with platinum-based regimens) improved survival. Response to NACT could be considered a surrogate endpoint of survival. Conclusions Age, International Federation of Gynecology and Obstetrics stage III/IV, lymph-node involvement, and type of NACT administered have a significant impact on survival. Response to NACT is a good surrogate endpoint of survival in patients with LACC.

Effect of trabeculectomy and canaloplasty on intra-ocular pressure modifications after postural changes in open-angle glaucoma.

haemorrhage. Nine subjects presented recurrent subretinal haemorrhage during the follow-up period. As these new haemorrhages all developed more than 1 week postoperatively, they were likely caused by the underlying disease rather than the intervention. This study is limited by its noncomparative, non-randomized retrospective design and relatively short-term follow-up. The timing of the final follow-up visit was highly variable. Consequently, the results from the final followup are highly comparable to the results at 6 weeks (median: 55 days). The lack of a control group is another limitation of this study. However, our results compare favourably to those of other similar studies evaluating the natural course of submacular haemorrhage. A prospective case series by Cheung et al. (2013). indicated amedian improvement in VA of 0.20 LogMAR units after 6 months. Similarly, retrospective data collection of 86 eyes revealed a 10.5%VA improvement after 6 months (Chen et al. 1999). In summary, the results of this study indicate that our surgical approach may be an effective treatment for submacular haemorrhage displacement in AMD patients. The procedure improved the visual recovery. However, the visual outcome is limited by the underlying macular pathology. Larger multicentre randomized controlled studies are warranted to determine the therapeutic effect of this surgical approach.

Restoring platinum sensitivity in recurrent ovarian cancer by extending the platinum-free interval: Myth or reality?

The platinum‐free interval is the most important predictive factor of a response to subsequent lines of chemotherapy and the most important prognostic factor for progression‐free and overall survival in patients with recurrent epithelial ovarian cancer. A nonplatinum regimen is generally considered the most appropriate approach when the disease recurs very early after the end of chemotherapy, whereas platinum‐based chemotherapy is usually adopted when the platinum‐free interval exceeds 12 months. However, the therapeutic management of patients with intermediate sensitivity (ie, when the relapse occurs between 6 and 12 months) remains debatable. Preclinical and clinical data suggest that the extension of platinum‐free interval (using a nonplatinum‐based regimen) might restore platinum sensitivity, thus allowing survival improvement. The objective of this review was to critically analyze preclinical and clinical evidences supporting this hypothesis. Cancer 2017;123:3450‐9.

Topographic Optic Disc Changes After Successful Trabeculectomy Evaluated Using Spectral Domain Optical Coherence Tomography

PURPOSE To investigate topographic optic disc changes after surgical intraocular pressure (IOP) reduction in adults with open angle glaucoma (OAG). METHODS Optic discs of patients with advanced primary open angle or exfoliation glaucoma were imaged using optical coherence tomography within 1 week before trabeculectomy. Patients were rescanned 1 week, 1 month, and 1 year after surgery. Maximum cup depth (MCD), and average cup depth (ACD) were calculated. RESULTS Twenty-two eyes from 20 patients (age, 70.5 ± 10.6 years; average mean defect of visual field, -15.0 ± 9.8 dB) were followed up for 1 year. The IOP decreased from 22.1 ± 2.8 mmHg at baseline to 11.5±2.6 mmHg 1 year following surgery (P<0.001). One-week and 1-month postoperative IOPs were 11.2 ± 2.8 and 11.2 ± 3.5 mmHg, respectively (P<0.001). Compared to the baseline values (356 ± 172 μm), postoperative ACD showed a significant decrease at 1 week (312 ± 164 μm; P<0.001) and 1 month (338 ± 175 μm; P=0.007) after surgery, but not at 1 year (339 ± 176 μm; P=0.354). Similarly, MCD significantly decreased from baseline (477 ± 190 μm) 1 week (431 ± 203 μm; P=0.029) and 1 month (448 ± 198 μm; P=0.047) after the surgery, but not after 1 year (479 ± 188 μm; P=1.0). CONCLUSIONS Trabeculectomy reduces IOP in eyes with advanced OAG, which induces topographic optic disc changes. Such optic disc changes became less pronounced over time and were no longer detectable 1 year after surgery.

Radiosurgery for intracranial meningiomas: A systematic review and meta-analysis

BACKGROUND Radiosurgery(RS), both in single and multiple sessions, have been performed for intracranial meningiomas. Different aspects are still controversial on this field. The aim of this systematic review is to summarize the current literature on long-term efficacy and safety of RS for meningiomas. METHODS Online databases were searched for studies published until April 2015. The primary outcomes were disease control and progression-free-survival(PFS). The secondary outcomes were symptom control and radiation-induced toxicity. RESULTS The estimate of disease control rate ranged from 87.0% to 100.0% at 5 years and from 67.0% to 100.0% at 10 years. The PFS rate ranged 78.0%-98.9% and 53.1%-97.2% at 5 and 10 years, respectively. The overall symptom control was 92.3%, the overall toxicity was 8.1%. CONCLUSIONS RS can be considered a safe and effective treatment. Efforts are needed in standardizing the definition of local and symptom control and toxicity in order to properly compare different treatment schedules.

The prognostic role of tumor size in early breast cancer in the era of molecular biology

Background The prognosis of early breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors. Methods The primary objective is to evaluate the association between tumor dimensions and overall survival (OS) / disease free survival (DFS), in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated using the following formula: 4/3π x a x b x c. Results 341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52–31.651.2). 44 patients (12.9%) relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and molecular subtype. The multivariate analysis confirmed the statistically significant association only for molecular subtype (p 0.005), with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34–5.22). Likewise for OS, an association was shown by the multivariate analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46–5.49; p 0.002). Conclusions In our study, the only parameter that strongly influences survival is molecular subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria but on biological features.

Systematic review and meta-analysis on neuropsychological effects of long-term use of opioids in chronic non-cancer pain patients

Opioid treatments are often prolonged because of the pathology causing pain. We focused on the cognitive functions in patients with chronic pain treated with opioids. This topic is currently controversial, but in practice, the consequences are important in patients’ daily lives, social interactions, working ability, and driving.

A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma

BackgroundPatients with recurrent/metastatic uterine leiomyosarcoma (U-LMS) have a dismal prognosis. This phase II study aims to evaluate trabectedin efficacy and safety in advanced U-LMS.MethodsEligible patients had received ≥ one line of chemotherapy. Gemcitabine ± docetaxel naive patients were randomised to Arm A: trabectedin 1.3 mg/m2 or calibration Arm B: gemcitabine 900 mg/m2 and docetaxel 75 mg/m2. Patients who had already received gemcitabine ± docetaxel directly entered Arm A. Primary end-point: 6-month progression-free rate (PFS-6). The null hypothesis that the true PFS-6 = 14% was tested against a one-sided alternative. This design yielded a 5% type I error rate and 90% power when the true PFS-6 is 25%.ResultsOverall, 126 patients entered Arm A (45 from randomisation and 81 directly) and 42 Arm B. Arm A patients characteristics: median age = 57; ≥2 previous chemotherapy lines = 37.4%; metastatic disease = 93%. The study met the condition for trabectedin activity: PFS-6 = 35.2% (95% CI: 26.2–45). No difference in PFS by the number of previous chemotherapy lines emerged. Median OS = 20.6 months (IQR: 8–36.4). In Arm B, the PFS-6 = 51.5% (95% CI: 33.5–69.2). No toxic deaths occurred. In Arm A, only 4 patients interrupted treatment for toxicity.ConclusionsTrabectedin is active and well tolerated, retaining similar efficacy across one to three previous lines of chemotherapy.