Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI).

BACKGROUND: We evaluated the efficacy and safety of the nontaxane microtubule dynamics inhibitor eribulin plus the humanized anti-VEGF monoclonal antibody bevacizumab in a novel second-line chemotherapy scheme in HER2-negative metastatic breast cancer (MBC) patients progressing after first-line paclitaxel and bevacizumab. PATIENTS AND METHODS: This is a multicenter, single-arm, Simon's two-stage, phase II study. The primary endpoint was the overall response rate, considered as the sum of partial and complete response based on the best overall response rate (BORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate. RESULTS: A total of 58 of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% CI 14.5-37.3). The clinical benefit rate was 32.8% (95% CI 21.3-46.0). The median PFS was 6.2 months (95% CI 4.0-7.8), and median OS was 14.8 months (95% CI 12.6-22.8). Overall, adverse events (AEs) were clinically manageable and the most common AEs were fatigue, paresthesia, and neutropenia. Quality of life was well preserved in most patients. CONCLUSIONS: The results of this study suggest that second-line therapy with bevacizumab in combination with eribulin has a meaningful clinical activity and may represent a potential therapeutic option for patients with HER2-negative MBC.

Absolute basophil count is associated with time to recurrence in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p < 0.1, have been selected for the development of a multivariable model. RESULTS: A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09-1.54; p = 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence [second vs. lower quartile HR 1.42 (1.12-1.79); p = 0.003, third vs. lower quartile HR 1.26 (1.01-1.57); p = 0.041; upper vs. lower quartile HR 1.36 (1.1-1.68); p = 0.005]. The limitations of a retrospective study are applicable. CONCLUSION: Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications.

BACKGROUND: Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. METHODS: We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. RESULTS: We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P<0.0001) from 2001 to 2010. The mean number of prescribed mammograms, bone scans, abdominal ultrasound and chest X-rays ('routine tests'), and costs was unchanged. However, the number of CT, PET scans and MRI ('new tests')prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from [euro ]357 in 2001 to [euro ]830 in 2010 (P<0.0001). CONCLUSIONS: New test prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival.

Endometrioma size is a relevant factor in selection of the most appropriate surgical technique: a prospective randomized preliminary study.

OBJECTIVES: To assess and compare the ovarian reserve in patients with different-sized endometriomas undergoing cystectomy or ablative surgery in order to determine the best surgical approach to safeguard healthy ovarian tissue. STUDY DESIGN: Prospective randomized study on 48 patients with unilateral single ovarian endometriomas. Patients were allocated into two groups based on endometrioma size: <5cm (n=26, Group A, small endometriomas) and ≥5cm (n=22, Group B, large endometriomas). Each group was randomized to coagulation or excision treatment (1:1 ratio) before the procedure. Anti-Müllerian hormone (AMH) levels were evaluated before surgery and 3 months after surgery. RESULTS: Both ablation and excision resulted in a significant reduction in AMH level regardless of endometrioma size. A significant interaction effect was observed between endometrioma size and type of surgical technique (analysis of covariance p for interaction=0.039): in Group A, no significant difference was found between the two surgical techniques (-17.6±4.7% vs -18.2±10.6%), whereas in Group B, the excision group showed a significantly greater percentage decrease in AMH level compared with the ablation group (-24.1±9.3% vs -14.8±6.7%, p=0.011). CONCLUSIONS: Both ablative and excision treatment of endometriomas have a negative effect on ovarian function. Endometrioma size is associated with the magnitude of ovarian reserve damage following excision treatment, but in the case of ablative treatment, the decrease in AMH serum level is independent of the size of the cyst. In surgical treatment of large endometriomas, the decrease in AMH level is more consistent and much more severe following cystectomy than ablation.

Sutureless hernioplasty with light-weight mesh and fibrin glue versus Lichtenstein procedure: a comparison of outcomes focusing on chronic postoperative pain.

PURPOSE: Groin hernia is one of the most common disease requiring surgical intervention (8-10% of the male population). Nowadays, the application of prosthetic materials (mesh) is the technique most widely used in hernia repair. Although they are simple and rapid to perform, and lower the risk of recurrence, these techniques may lead to complications. The aim of the present study is to assess the incidence and degree of chronic pain, as well as the impairment in daily life, in two procedures: (1) the "Lichtenstein technique" with polypropylene mesh fixed with non-absorbable suture, and (2) the "sutureless" technique carried out by using a partially absorbable mesh (light-weight mesh) fastened with fibrin glue. METHODS: This was a study conducted over a period of 3 years from July 2006 to July 2009. A total of 148 consecutive male patients suffering from groin hernia were divided randomly into two groups: (1) Group A: patients operated with "sutureless" technique with partially absorbable mesh and plug fastened with 1 ml haemostatic sealant; (2) Group B: patients operated with Lichtenstein technique using non-absorbable mesh and plug anchored with polypropylene suture. Follow-up took place after 7 days, and 1, 6 and 12 months and consisted of examining and questioning patients about chronic pain as well as the amount of time required to return to their normal daily activities. RESULTS: No major complications or mortality were observed in either group. In group A there was a faster return to work and daily life activities. Six patients (7.8%) in group B suffered from chronic pain, whereas no patient in group A demonstrated this feature. CONCLUSIONS: Our experience shows that the combined use of light-weight mesh and fibrin glue gives significantly better results in terms of postoperative pain and return to daily life.

Congenital cataract extraction with primary aphakia and secondary intraocular lens implantation in the posterior chamber.

PURPOSE: To evaluate visual outcomes, eye movement abnormalities, and postoperative complications after secondary posterior chamber intraocular lens (IOL) implantation in aphakic children who had initial LAC correction. METHODS: A retrospective study was carried out on 53 patients (94 eyes). Following aphakic surgery and LAC correction the patients received secondary IOL implantation in the posterior chamber. Special attention was paid to factors that may have influenced their visual outcomes, such as eye movement abnormalities, cataract unilaterality, and cataract density. RESULTS: No association was found between age at surgery and the onset of strabismus (p=0.611) or with visual acuity (p=0.086). However, unilaterality and total cataract density were found to have a negative association with poor vision (p<0.001). Strabismus and nystagmus were found to have a statistically significant negative association with visual acuity (p=0.002). Posterior capsule opacification occurred in six eyes of five patients following cataract extraction; IOL dislocation occurred in four eyes after IOL intraocular implantation, and secondary glaucoma occurred in one eye. CONCLUSIONS: IOL implantation before 12 months of age may be useful in unilateral cataract; in bilateral cataract, simultaneous surgical aphakia, LAC correction, and then IOL implantation at 2.5-3 years of age, together with anti-amblyopic therapy when strabismus or asymmetric cataract density occur, are efficient methods to obtain visual recovery. Extraocular muscle surgery may be required to correct strabismus.

Strabismus in developmental cataract.

PURPOSE: To evaluate the presence of strabismus in patients with developmental cataract rendered pseudophakic and how this influences their visual acuity. METHODS: A retrospective study was carried out on 113 patients with developmental cataract who came under the authors' observation at the outpatient department of the Pediatric Ophthalmology Unit of the University of Federico II of Naples from 1990 to 2005. All patients were followed up for a long period (mean 62 months, range 36-144 months). Age at diagnosis, sex, laterality, age at cataract extraction, morphology, and cataract density were all considered as possible factors associated with strabismus. Visual acuity and ocular motility before and after cataract extraction surgery were especially noted. Statistical evaluation was performed using t-test, Chi-square test, and Fisher exact test. RESULTS: Out of the 113 patients a total of 181 eyes were affected: 68 patients (60%) presented bilateral cataract, 45 patients (40%) monolateral cataract. Strabismus was present in 39 patients (34%) before cataract surgery. Age at cataract diagnosis, age at surgery, sex, and cataract morphology were not found to be statistically associated with strabismus. However, laterality was found to be statistically associated with the onset of strabismus. Cataract density was found to be statistically associated with poor vision. Patients with strabismus presented a non statistically significant lower visual acuity. CONCLUSIONS: Strabismus has a greater incidence in developmental cataract compared to the general population, and can influence visual acuity, especially in monolateral and total cataracts. Intraocular lens implants produced satisfactory visual rehabilitation.

Activation of p38 MAPKinase/cPLA2 pathway in homocysteine-treated platelets.

Hyperhomocysteinemia is considered a risk factor in arterial and venous thrombosis. The mechanism by which homocysteine (HCy) supports atherothrombosis is still unknown and may be multifactorial. Earlier in vitro studies demonstrated that HCy induced arachidonic acid release and increased thromboxane B2 (TXB2) formation. In this work, we found that HCy stimulated the rapid and sustained phosphorylation of platelet p38 mitogen-activated protein kinase (p38 MAPK). The effect was time- and dose-dependent. The HCy effect on p38 MAPK phosphorylation was prevented by N-acetyl-L-cysteine and iloprost and was partially inhibited by nordihydroguaiaretic acid. Moreover, the incubation of platelets with HCy led to the phosphorylation of cytosolic phospholipase A2 (cPLA2). In addition HCy promoted cPLA2 activation, assessed as arachidonic acid release. The cPLA2 phosphorylation and activation were both impaired by the inhibition of p38 MAPK through SB203580. This effect was not complete, reaching at the most the 50% of the total. In FURA 2-loaded platelets, HCy induced a dose-dependent intracellular calcium rise suggesting that the calcium elevation promoted by HCy could participate in the cPLA2 activation, leading to arachidonic acid release and TXB2 formation. In conclusion, our data provide insight into the mechanisms of platelet activation induced by HCy, suggesting that the p38 MAPK/cPLA2 pathway could play a relevant role in platelet hyperactivity described in hyperhomocysteinemia.