Exploratory study on the effects of biodegradable nanoparticles with drugs on malignant B cells and on a human/mouse model of Burkitt lymphoma

The aim of this study was to determine if Rituximab coated Biodegradable Nanoparticles (BNPs) loaded with Chlorambucil and Hydroxychloroquine could induce apoptosis of B-Chronic Lymphocytic Leukemia (B-CLL), MEC-1 and BJAB cells in vitro and evaluate their toxic and therapeutic effects on a Human/Mouse Model of Burkitt Lymphoma at an exploratory, proof of concept scale. We found that Rituximab-Chlorambucil-Hydroxychloroquine BNPs induce a decrease in cell viability of malignant B cells in a dose-dependent manner. The mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the B-CLL cells after Annexin V/propidium iodide staining. Additional data revealed that these BNPs were non toxic for healthy animals, and had prolonged survival in this mice model of human lymphoma.     

Contrast-enhanced ultrasound: a filter role in AJCC stage I/II melanoma patients

One of the most significant advances in melanoma staging is sentinel lymph node biopsy (SLNB). It is a surgical technique to detect occult nonpalpable micrometastases in regional lymph nodes. Recently, contrast-enhanced ultrasound (CEUS) was introduced as a noninvasive procedure, in spite of SLNB, for the detection of SLNs in patients with cutaneous melanoma. The main purpose of this study was to evaluate the diagnostic accuracy of CEUS in the diagnostic workup of patients with melanoma in comparison with the final histology of SLNs detected through preoperative lymphoscintigraphy. Fifteen patients with cutaneous melanoma underwent prompt excisional biopsy with narrow margins in order to avoid impairment of the melanoma lymphatic basin and were referred for SLNB according to routine indications between January and February 2009. In our study CEUS showed, albeit based on a small patient sample, a negative predictive value of 100%, that means that all negative results were confirmed by negative SLN histopathological examination; all ultrasonographically negative lymph nodes corresponded to nonmetastatic sentinel nodes.     

Uninfected Para-Anastomotic Aneurysms after Infrarenal Aortic Grafting

Purpose

This single-institution retrospective review examines the management of uninfected para-anastomotic aneurysms of the abdominal aorta (PAAA), developed after infrarenal grafting.

Materials and Methods

From October 1979 to November 2005, 31 PAAA were observed in our Department. Twenty-six uninfected PAAA of degenerative etiology, including 24 false and 2 true aneurysms, were candidates for intervention and retrospectively included in our database for management and outcome evaluation. Six (23%) patients were treated as emergencies. Surgery included tube graft interposition (n = 12), new reconstruction (n = 8), and graft removal with extra-anatomic bypass (n = 3). Endovascular management (n = 3) consisted of free-flow tube endografts.

Results

The mortality rate among the elective and emergency cases was 5% and 66.6%, respectively (p = 0.005). The morbidity rate in elective cases was 57.8%, whereas 75% in emergency cases (p = 0.99). The survival rate during the follow-up was significantly higher for elective cases than for emergency cases.

Conclusion

Uninfected PAAA is a late complication of aortic grafting, tends to evolve silently and is difficult to diagnose. The prevalence is underestimated and increases with time since surgery. The mortality rate is higher among patients treated as an emergency than among patients who undergo elective surgery, therefore, elective treatment and aggressive management in the case of pseudoaneurysm are the keys to obtain a good outcome. Endovascular treatment could reduce mortality. Patients who undergo infrarenal aortic grafting require life-long surveillance after surgery.     

Solitary fibrous tumor of the pelvis: an uncommon soft-tissue tumor. A case report

A rare case of Solitary fibrous tumor (SFT) of the pelvis is reported. A 76-years-old man presented with a low abdominal pain, acute urine retention and constipation. Imaging studies (US, CT MR) showed an 17 x 10 x 9 ovoid mass in the pelvis, dislocating bladder and rectum. Finally, trans-rectal needle biopsy suggested the diagnosis of SFT. En bloc excision of tumor and rectum (because of strong adhesions) was performed. Histological examination showed spindle and fibroblastic-like cells dispersed in collagenous areas with positive stains for CD34, bcl-2, CD99 and it confirmed diagnosis of SFT. No postoperative complications occurred, only vesico-sphincter dyssynergia was found by urodynamics. After 5 years, patient is disease-free. SFT is, usually, benign tumor with slow growth and excellent prognosis. Complete surgical resection is the only curative treatment. However, 10-15% of SFT are malignant and histological findings cannot always predict clinical behaviour. For this reason, careful and long term follow-up is necessary after surgery.     

Hemofiltration and Hemodiafiltration Reduce Intradialytic Hypotension in ESRD

Symptomatic intradialytic hypotension is a common complication of hemodialysis (HD). The application of convective therapies to the outpatient setting may improve outcomes, including intradialytic hypotension. In this multicenter, open-label, randomized controlled study, we randomly assigned 146 long-term dialysis patients to HD (n = 70), online predilution hemofiltration (HF; n = 36), or online predilution hemodiafiltration (HDF; n = 40). The primary end point was the frequency of intradialytic symptomatic hypotension (ISH). Compared with the run-in period, the frequency of sessions with ISH during the evaluation period increased for HD (7.1 to 7.9%) and decreased for both HF (9.8 to 8.0%) and HDF (10.6 to 5.2%) (P < 0.001). Mean predialysis systolic BP increased by 4.2 mmHg among those who were assigned to HDF compared with decreases of 0.6 and 1.8 mmHg among those who were assigned to HD and HF, respectively (P = 0.038). Multivariate logistic regression demonstrated significant risk reductions in ISH for both HF (odds ratio 0.69; 95% confidence interval 0.51 to 0.92) and HDF (odds ratio 0.46, 95% confidence interval 0.33 to 0.63). There was a trend toward higher dropout for those who were assigned to HF (P = 0.107). In conclusion, compared with conventional HD, convective therapies (HDF and HF) reduce ISH in long-term dialysis patients.Hemodialysis (HD) is not an effective treatment for long-term dialysis patients with stage 5 chronic kidney disease (CKD), and their comorbidities, including intradialytic symptomatic hypotension (ISH), are persistently very high,¹ possibly contributing to their high mortality rate.² Convective treatments (CTs)—increasing “middle molecule” removal and removing fluids by more physiologic convection—have been suggested for improving dialysis patient outcomes including the reduction of ISH.^3,4 Observational studies have consistently suggested that high-flux treatments for long-term dialysis patients with stage 5 CKD are associated with reduced morbidity and mortality.^5–8 The Hemodialysis (HEMO) Study,⁹ a landmark randomized, controlled trial designed to test the effect of membrane flux and dialysis dosage on mortality, showed that high-flux HD is associated with a nonsignificantly lower relative mortality risk of 8%, although a secondary analysis suggested a significant advantage of high-flux membranes in patient subgroups. More recently, the Membrane Permeability Outcome (MPO) study¹⁰ found that survival could be significantly improved by using high-flux as compared with low-flux membranes in high-risk patients identified by serum albumin of ≤4 g/dl as well as in patients with diabetes in a post hoc analysis. By extrapolating the experimental results of these multicenter studies, it can be hypothesized that the benefits could be even greater by further increasing convection in treating long-term dialysis patients with stage 5 CKD. The number of randomized, prospective trials that have compared CTs with standard HD is still very low, and no conclusive data are available concerning the effect of CTs in their various forms on morbidity and survival in long-term dialysis patients with stage 5 CKD.It is very interesting to observe that the concept of dialysis adequacy has now widened to include not only urea kinetics¹¹ but also middle and high molecule removal^12,13 and biocompatibility.¹⁴ Locatelli et al.,¹⁵ in a controlled randomized multicenter study involving 380 patients, compared four treatment dialysis modalities: Low-flux Cuprophan HD, low-flux polysulfone HD, high-flux polysulfone HD, and high-flux polysulfone hemodiafiltration (HDF). Although a reduction in predialysis β-2 microglobulin levels in high-flux HD and HDF compared with low-flux HD was found, no differences were reported in treatment tolerance; however, the number of symptomatic treatments were far fewer than expected, thus reducing the statistical power of the study. Canaud et al.¹⁶ analyzed the data from Dialysis Outcomes and Practice Patterns Study (DOPPS) and reported that survival was associated with the amount of convection.Two prospective clinical trials performed by the Sardinian Collaborative Group^3,4 compared the clinical effects of (bicarbonate) high-flux HD and predilution online (bicarbonate) HF in clinically stable patients, with different³ and similar⁴ equilibrated Kt/V (eKt/V) and treatment times. Polyamide membranes, ultrapure fluid with similar electrolyte composition, and the same dialysis machine were used in both studies. These studies showed fewer symptoms, including hypotension in HF as compared with HD also in clinically stable small-sized patient groups. A third prospective collaborative study performed by the same collaborative group comparing HF with HDF¹⁷ in a group of 39 stable patients, after a run-in treatment period of 6 months on low-flux HD, found that HF was more effective in reducing the frequency of hypotension. On the basis of the results of these Sardinian studies, we planned a prospective, multicenter randomized study to compare low-flux HD with online predilution HF and/or HDF to evaluate the sessions with ISH of two different types and dosages of convection in comparison with HD, as routinely performed by investigators in day-to-day clinical practice.     

Retinoblastoma protein expression predicts response to bacillus Calmette-Guérin immunotherapy in patients with T1G3 bladder cancer

ObjectivesBacillus Calmette-Guérin (BCG) immunotherapy is regarded as the current treatment of choice for stage T1 grade 3 (T1G3) bladder cancer (BC), though its efficacy is limited by high recurrence and progression rate. Identification of molecular prognosticators that might be helpful in discriminating between responders and nonresponders to BCG treatment is therefore of major clinical importance; thus we focused on the cell-cycle related retinoblastoma protein (pRB), which had been already investigated in bladder cancer. The goal of our study was specifically to address whether its expression predicts the outcomes of BCG treatment for patients with T1G3 disease.Materials and MethodsTo address this issue, paraffin-embedded specimens of 27 patients having undergone transurethral resection of T1G3 BC and intravesical instillations of BCG (induction + 1 year maintenance) were immunostained with pRB monoclonal antibody. Patients in whom the bladder muscle was not clearly visible, and healthy, as well as patients with TaG3 tumors or with concomitant carcinoma in situ were excluded. Mean follow-up was 60 months (range 15–135).ResultsThirteen tumors showed normal (1% to 50% labeling index) while 14 showed altered pRB expression, consisting of no expression (0% labeling index) in six and overexpression (>50% labeling index) in eight. Recurrence occurred in 10 (37%) patients and mean time to recurrence was 22.8 months (range 6–48). Recurrence rate was 57% in patients with altered and 15% in those with normal pRB expression, with a statistically significant difference in disease-free survival (P = 0.037). Progression occurred in five (18.5%) patients and mean time to progression was 24 months (range 6–48). Progression rate was 36% in patients with altered and 0% in patients with normal pRB expression, with a statistically significant difference in progression-free survival (P = 0.018).ConclusionsIn this homogeneous population of T1G3 bladder tumors, altered pRB expression predicted recurrence and progression after BCG treatment. These findings outline the potential role of pRB immunostaining in predicting T1G3 BC response to BCG immunotherapy.     

Failure of the Patellar Tendon with the Patella Everted versus Noneverted in a Matched-Pair Cadaver Model

Avoidance of patellar eversion during total knee arthroplasty may help to prevent injury to the patellar tendon. The purpose of this study was to compare the load-to-failure of the everted versus the noneverted patella in a cadaveric model. Fourteen cadaver knees (seven pairs) were loaded to failure with the patella everted in one knee and not everted in the other. Mean load-at-ultimate failure in the patella-everted group was 1,111 ± 572 N, and in the patella-noneverted group was 1,621 ± 683 N (p = 0.01). Additionally, loads-at-initial-partial failure were lower (p = 0.04) in the patella-everted compared to the patella-noneverted group, 573 ± 302 N versus 1,115 ± 358 N, respectively. A partial failure of the patellar tendon occurred in 100% of the everted specimens, whereas only 57% of the noneverted specimens had partial failure. These findings suggest patella eversion may lead to failure of the patellar insertion at lower loads than when the patella is not everted.     

Microbiological evaluation of tissue expanders in patients who had first stage breast reconstruction

Capsular contracture is one of the most common complications associated to the use of foreign materials in reconstruction after mastectomy and aesthetic breast augmentation. Many risk factors, causes, and conditions seldom associated with capsular contracture have been identified but none of these have been confirmed by published data. Among these, subclinical infections (particularly those caused by Staphylococcus epidermidis) seem to be one of the most likely. In the present study we analysed the correlation between capsular contracture and the incidence of periprosthetic subclinical infection in two groups of patients who had first-stage breast reconstruction: one group of patients who were not having adjuvant or neoadjuvant radiotherapy for breast cancer (n = 25) and a second group of patients who had had quadrantectomy and radiotherapy (QUART) and successive radical mastectomy for recurrent disease (n = 25). Patients who had radiotherapy had a significantly higher incidence of subclinical infection (n = 13) than patients who did not (n = 1), but there was no statistical correlation between subclinical infection and capsular contracture. Subclinical infections seemed to present at a later stage and under certain local and systemic circumstances that favoured bacterial growth, such as radiotherapy.