Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called “cold tumors” still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination with IT.     

Radiographic Analysis of Graft Dimensional Changes in Transcrestal Maxillary Sinus Augmentation: A Retrospective Study

Background. The maxillary sinus lift is a popular and predictable technique associated with implant-supported rehabilitation of the severely atrophic maxilla. The aim of the present retrospective study was to investigate the effectiveness of transcrestal maxillary sinus augmentation and the graft resorption pattern using different heterologous bone substitutes. Methods. A total of 75 sinus-grafting procedures were performed and 89 implants were placed in 66 patients, 24 males and 42 females, with mean age 67.9 ± 10.64 years (range 43–84 years). Nineteen subjects were smokers. The mean follow-up period was 93.33 ± 54.71 months (range 14–240 months). Clinical and radiographical evaluations were performed. Graft height and width were measured at baseline and at the latest follow-up. Results. Mesiodistal and vertical resorption averaged 9.3 ± 20.7% (standard deviation), and 5.04 ± 9.9% of the postoperative size, respectively, considering the graft as the unit. Linear regression analysis showed that graft resorption in both the vertical and the mesiodistal dimension is independent of the follow-up time. Conversely, there was a trend for greater resorption when increasing the postoperative graft size, in both vertical (p = 0.001) and horizontal (p = 0.007) dimensions. When grouping the dimensional changes by graft particle size (only small (<300 μm) particles, combination of small and medium (>500 μm)/large (>1000 μm) particles, and only medium/large particles), there was a trend for greater resorption associated with smaller particles, but it was not significant; neither in the mesiodistal nor in the vertical dimension (p = 0.17 and p = 0.25, respectively). No implant was lost during the observation period. In conclusion, the transcrestal technique for maxillary sinus augmentation documented a high level of predictability. The low clinical morbidity and the contextual dental implant positioning is clinically useful in relation to a significant reduction of the time required for implant restoration, a consistent decrease of the number of surgical phases, and a cost-effectiveness approach for the rehabilitation. The graft resorption pattern in all cases was compatible with persistent implant protection and support.     

Production of Dense Cu-10Sn Part by Laser Powder Bed Fusion with Low Surface Roughness and High Dimensional Accuracy

Tin-bronze alloys with a tin content of at least 10 wt% have excellent mechanical properties, wear resistance, and corrosion resistance. Among these alloys, Cu-10Sn was investigated in this study for production with the laser powder bed fusion process with a 500W Yb:YAG laser. In particular, a design of experiment (DoE) was developed in order to identify the optimal process parameters to obtain full density, low surface roughness, and high dimensional accuracy. Samples were characterized with Archimedes’ method and optical microscopy to determine their final density. It was shown that the first method is fast but not as reliable as the second one. A first mechanical characterization was performed through microhardness tests. Finally, a set of process parameters was identified to produce fully dense samples with low surface roughness and high accuracy. The results showed that the volumetric energy density could represent an approach that is too simplified, therefore limiting the direct correlation with the physical aspects of the process.     

Analysis of survival after pancreatic resection for oncological pathologies

Surgical treatment of pancreatic cancer is to date the only modality that offers a chance of long-term survival. Potentially curative surgery is an option for only about 15% of patients with pancreatic adenocarcinoma. The aim of this study was to determine the survival and to assess the association of clinical, pathological, and treatment features with survival of patients who underwent resection of pancreatic cancer at the Department of Surgery of Udine University Hospital. From November 1989 to December 2005, 137 consecutive patients, who underwent surgical procedures for pancreatic cancer, were followed in our department. We performed 76 pancreatico-duodenectomy, 26 distal pancreatectomies and 35 total pancreatectomies. The surgical reconstruction after pancreatico-duodenectomy was as follows: 11 closures of the main duct with manual nonabsorbable stitches, 24 closures of the main duct with a linear stapler, 17 occlusions of the main duct with neoprene glue and 24 duct-to-mucosa anastomoses. Mean survival time was 27.7 +/- 26.93 months (mean +/- SD) and mean disease-free survival time was 25.4 +/- 23.06 months (mean +/- SD). 1, 3, 5, 7 and 9-year survival rates were 63.9, 33.7, 21.17, 12.7 and 10.2%, respectively. Significant differences in survival were recorded by the Log-rank test for age > 70 (p = 0.001), surgical procedures (p = 0.00046) and presence of metastases (p = 0.0055) The treatment of pancreatic cancer is undertaken with two different aims. The first is radical surgery for patients with early-stage disease, mainly stage I and partly stage II. In all other cases, the aim of treatment is the palliation of the several distressing symptoms related to this cancer. The standard treatment option for resectable tumours is radical pancreatic resection according to the Whipple procedure or total pancreatectomy.     

Dynamic Hotelling duopoly with linear transportation costs

I investigate a spatial duopoly model with linear transportation costs as a differential game where product differentiation is the result of firms' R&D investments. Two related results obtain, i.e. (i) the steady‐state R&D investment (product differentiation) is negatively (positively) related to the cost of capital and time discounting; and (ii) if time discounting and the cost of capital are sufficiently high, the amount of differentiation observed in steady state is sufficiently large to ensure the existence of a unique pure‐strategy price equilibrium with prices above marginal cost. The range of time discounting wherein the game produces a price equilibrium in pure strategies is wider under the closed loop solution than under the open loop solution. Copyright © 2011 John Wiley & Sons, Ltd.     

Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G

In the inflammatory response, leukocyte rolling before adhesion and transmigration through the blood vessel wall is mediated by specific cell surface adhesion receptors. Neutrophil rolling involves the interaction of P-selectin expressed on activated endothelium and its counter-receptor on neutrophils, P-selectin glycoprotein ligand-1 (PSGL-1). Here, it is reported that P-selectin binding to neutrophils is lost under conditions that cause the release of proteinases from neutrophil primary granules. Treatment of neutrophils with the purified neutrophil granule proteinases, cathepsin G and elastase, rapidly abolished their capacity to bind P-selectin. This inactivation corresponded to loss of the N-terminal domain of PSGL-1, as assessed by Western blot analysis. A loss of intact PSGL-1 protein from the surfaces of neutrophils after the induction of degranulation was also detected by Western blot analysis. Cathepsin G initially cleaved near the PSGL-1 N-terminus, whereas neutrophil elastase predominantly cleaved at a more C-terminal site within the protein mucin core. Consistent with this, cathepsin G cleaved a synthetic peptide based on the PSGL-1 N-terminus between Tyr-7/Leu-8. Under conditions producing neutrophil degranulation in incubations containing mixtures of platelets and neutrophils, the loss of PSGL-1, but not P-selectin, from platelet-neutrophil lysates was detected. Cathepsin G- or neutrophil elastase-mediated PSGL-1 proteolysis may constitute a potential autocrine mechanism for down-regulation of neutrophil adhesion to P-selectin.     

Participation of endogenous catecholamines in the regulation of left ventricular mass in progeny of hypertensive parents

To investigate whether adrenergic activity is a determinant of left ventricular hypertrophy in human hypertension, in each of 10 normotensive subjects with two hypertensive parents we have examined the relationship between changes in echocardiographic parameters of left ventricular anatomy and those in circulating catecholamine levels induced by three, 3 week periods of different sodium and potassium intakes. A high sodium-normal potassium regimen induced a significant reduction in upright plasma norepinephrine (from 599 +/- 89 to 379 +/- 45 pg/ml, p less than .01) and in posterior wall (PWT) and interventricular septal (IVST) thickness, as well as in the left ventricular mass index (LVMi). Changes in upright plasma norepinephrine concentrations correlated with those in IVST (r = .822, p less than .01) and in LVMi (r = .833, p less than .01). A low sodium-normal potassium diet resulted in increases in supine and upright plasma norepinephrine levels (from 356 +/- 44 to 488 +/- 89 pg/ml, p less than .001; and from 565 +/- 42 to 744 +/- 33 pg/ml, p less than .01) as well as increases in IVST and LVMi (from 97 +/- 7 to 107 +/- 7 g/m2, p less than .001). The changes in norepinephrine levels in supine and upright subjects correlated with changes in IVST (r = .836, p less than .01 and r = .796, p less than .01) and in LVMi (r = .931, p less than .001 and r = .947, p less than .001). No significant change in plasma catecholamine concentrations or in PWT, IVST, or LVMi was detected after a low sodium-high potassium regimen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous transluminal renal angioplasty in patients with solitary kidney

We report our experience with percutaneous transluminal angioplasty of renal arteries (PTRA) in solitary kidney patients. Our series includes 31 patients (mean age: 52 years). 7 with solitary kidney following surgical nephrectomy and 24 with functioning solitary kidney. PTR indicated in presence of stenoses ranging from 60–95 % of vessel lumen. Procedure, with 29 patients were technically successful and mean values for stenosis dropped from 77 % to 33 %. In order to assess the results technically, changes in arterial blood pressure (according to Martin's classification) and creatinine levels were considered. Of 25 followed-up patients, 13 were cured (52%), 8 improved (32%),and 4 were unchanged (16%%). Complications were observed during procedures in five patients (16. 1 % ), superimposing that of nonsolitary kidney patients. Good revasculariiation, reduction of blood pressure, preservation or even improvement of renal function and low complications, make PTRA the best procedure with solitary kidney patients.