Concurrent blockade of different checkpoint receptors, notably PD-1 and CTLA-4, elicits greater anti-tumor activity for some tumor types, and the combination of different checkpoint receptor ...inhibitors is an active area of clinical research. We have previously demonstrated that anti-tumor vaccination, by activating CD8 + T cells, increases the expression of PD-1, CTLA-4, LAG-3 and other inhibitory receptors, and the anti-tumor efficacy of vaccination can be increased with checkpoint blockade. In the current study, we sought to determine whether anti-tumor vaccination might be further improved with combined checkpoint blockade. Using an OVA-expressing mouse tumor model, we found that CD8 + T cells activated in the presence of professional antigen presenting cells (APC) expressed multiple checkpoint receptors; however, T cells activated without APCs expressed LAG-3 alone, suggesting that LAG-3 might be a preferred target in combination with vaccination. Using three different murine tumor models, and peptide or DNA vaccines targeting three tumor antigens, we assessed the effects of vaccines with blockade of PD-1 and/or LAG-3 on tumor growth. We report that, in each model, the anti-tumor efficacy of vaccination was increased with PD-1 and/or LAG-3 blockade. However, combined PD-1 and LAG-3 blockade elicited the greatest anti-tumor effect when combined with vaccination in a MycCaP prostate cancer model in which PD-1 blockade alone with vaccination targeting a "self" tumor antigen had less efficacy. These results suggest anti-tumor vaccination might best be combined with concurrent blockade of both PD-1 and LAG-3, and potentially other checkpoint receptors whose expression is increased on CD8 + T cells following vaccine-mediated activation.
•Joint congruity in tibial plateau fractures are fundamental, but a good posterior reduction is not achievable with standard approaches.•Frosch approach provides a good view of the back of the joint ...but is burdened by a large skin incision and not expose the lateral tibia.•Our modification of the Frosch approach provides an “S-shaped” incision that allows to better expose and control the CPN and the fracture.
Achieving the best possible articular congruity following a tibial plateau (TP) fracture is associated with better long-term functional outcomes; TP has an essential role in the movements of the knee joint and is well established that a not optimal reduction leads to articular instability and early osteoarthritis.
In recent times, 3D reconstruction from CT scan has greatly contributed to improve the surgical treatment of these fractures since an accurate preoperative plan gives the possibility to decide the best interventional strategy before the surgical incision.
Reduction of the posterior part of tibial plateau is not easily achievable with standard surgical access.
Several posterolateral approaches, proposed by authors such as Frosch and Lobenhoffer, have been described over the years; these approaches can be divided into 2 groups: with or without osteotomy of the fibula.
Main disadvantages of these techniques are the large skin incision, the difficulty of exposing the lateral part of the tibia, the high frequency of damages of the posterolateral TP corner, and in some cases the necessity of performing fibular head osteotomy.
The surgical approach presented in this paper is a simple innovation of the well-known Frosch approach: skin incision is about 12 centimeters in length and runs in a “S” shape with the center positioned over the head of the fibula. It starts 2 centimeters laterally to the tibial crest 6 centimeters below the tibial tuberosity and is directed proximally, curving posteriorly at the level of fibular head and returning straight in the most proximal part; it terminates 4 centimeters posteriorly the lateral femoral condyle.
This innovative approach allows the trauma surgeon to achieve an optimal exposure and control of posterior tibial plateau fractures, with the great advantage of being able to treat the lateral tibial plateau with the same surgical incision.
Background
In the last decade, the number of prosthetic joint replacements has been rising each year and this growing trend is related to the increased number of prosthetic joint infections (PJI). As ...PJI represent a devastating condition for the patient, physicians must identify the best treatment option for each case. Guidelines are not always clear regarding the most appropriate therapy pathway as they differ in many parameters.
Materials and methods
Aim of this article is to compare the different indications as reported by four major Academic Societies: the Infectious Disease Society of America, the American Academy of Orthopaedic Surgeons, and the Musculoskeletal Infection Society (MSIS) which published the guideline in partnership with the European Bone And Joint Infection Society.
Conclusions
PJI Guidelines differ in many parameters, therefore the choice of treatment for each case does not appear immediate; it would be desirable that, in the next few years, new scientific evidence will help clarify the indications of the most effective therapeutic protocols for PJI to determine the ultimate surgical strategy for every single patient.
The purpose of this study is to evaluate the efficacy and safety of unidirectional barbed suture (V-Loc) compared to a standard monofilament stitch (Vicryl) in suturing of a free flap to local tissue ...after head and neck surgery for squamous cell carcinoma of the oral cavity. Complication rates, operative closure time, length of hospitalisation and costs were evaluated. The study cohort (group A) of 20 consecutive patients reconstructed using barbed stitches for suturing was prospectively compared to a control cohort (group B) of 20 consecutive patients reconstructed using conventional vicryl stitches. All patients were affected by squamous cell carcinoma of the tongue and underwent different types of glossectomy and reconstruction with free flaps. This analysis demonstrates the efficacy of the barbed suture compared with a standard monofilament stitch in terms of lower complication rate (15% group A, 30% group B), intra-operative closure times (486 minutes group A, 517 minutes group B), and length of hospitalisation (average length of hospitalisation 14.60 days group A, 16.85 days group B). These factors coupled with the use of a lower number of stitches compared with the standard stitches may compensate the increased cost of the barbed suture. In conclusion, this study demonstrates that the use of unidirectional barbed stitches for suturing of a free flap to the recipient site reduces the complication rate, principally in terms of dehiscence and fistula incidence, and reduces intra-operative time and length of hospitalisation. Based on these results and on the literature, the use of unidirectional barbed stitches can be considered as a safe and efficient alternative to conventional stitches for suturing of free flaps to local tissue.
Highlights • Nowadays there are no specific indicators for IMRT//IGRT Radiotherapy techniques. • Two structure, 10 processe and 2 outcome QIs were elaborated. • Data from four Italian Centers were ...collected and used for validation. • Seven indicators were completely new. A new standard is proposed for four indicators.
Purpose
Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15–30% of cases, therefore it ...would be useful to assess if pretreatment of
18
F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC.
Methods
Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models.
Results
In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index).
Conclusions
If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.
Purpose and objective
To test the hypothesis that a rectal and bladder preparation protocol is associated with an increase in prostate cancer specific survival (PCSS), clinical disease free survival ...(CDFS) and biochemical disease free survival (BDFS).
Patients and methods
From 1999 to 2012, 1080 prostate cancer (PCa) patients were treated with three-dimensional conformal radiotherapy (3DCRT). Of these patients, 761 were treated with an empty rectum and comfortably full bladder (RBP) preparation protocol, while for 319 patients no rectal/bladder preparation (NRBP) protocol was adopted.
Results
Compared with NRBP patients, patients with RBP had significantly higher BDFS (64% vs 48% at 10 years, respectively), CDFS (81% vs 70.5% at 10 years, respectively) and PCSS (95% vs 88% at 10 years, respectively) (log-rank test
p
< 0.001). Multivariate analysis (MVA) indicated for all treated patients and intermediate high-risk patients that the Gleason score (GS) and the rectal and bladder preparation were the most important prognostic factors for PCSS, CDFS and BDFS. With regard to high- and very high-risk patients, GS, RBP, prostate cancer staging and RT dose were predictors of PCSS, CDFS and BDFS in univariate analysis (UVA).
Conclusion
We found strong evidence that rectal and bladder preparation significantly decreases biochemical and clinical failures and the probability of death from PCa in patients treated without daily image-guided prostate localization, presumably since patients with RBP are able to maintain a reproducibly empty rectum and comfortably full bladder across the whole treatment compared with NRPB patients.