Flow stability in a wide vaneless diffuser

Abstract This work is concerned with the theoretical aspects of flow stability in a two dimensional vaneless diffuser. Specifically, the appearance of self-excited oscillations, also referred to as rotating stall, is investigated considering a two-dimensional inviscid flow in an annulus. We consider a linear perturbation method, taking as basic flow the steady potential velocity field whose radial and tangential components are inversely proportional to the radial coordinate. We show that such flow may become unstable to small two-dimensional perturbations provided that the ratio between the inlet tangential velocity and the radial one is sufficiently large and a certain amount of vorticity is injected in the flow field. Such an instability is purely kinematical, i.e. it does not involve any boundary layer effects, contrary to the classical hypothesis which ascribes the instability to a peculiar boundary layers interaction

Relevance of pharmacogenomics and multidisciplinary management in a young-elderly patient with KRAS mutant colorectal cancer treated with first-line aflibercept-containing chemotherapy

Introduction: Intensive oncological treatment integrated with resection of metastases raised the clinical outcome of metastatic colorectal cancer (MCRC). In clinical practice, complex evaluation of clinical (age, performance status, comorbidities), and biological (tumoral genotype, pharmacogenomic) parameters addresses tailored, personalized multidisciplinary treatment strategies. Patients with MCRC unsuitable for first-line intensive medical treatments are prevalent and showed worse clinical outcome. After progression to oxaliplatin-based chemotherapy, aflibercept/FOLFIRI significantly improved clinical outcome, even if no survival benefit was reported in adjuvant fast relapsers by aflibercept addition. The case reported a young-elderly (yE) patient with KRAS mutant colorectal cancer rapidly progressing to adjuvant chemotherapy, unfit owing to comorbidities, with multiple pharmacogenomic alterations, who gained long-term survival in clinical practice by multidisciplinary treatment strategy consisting of first-line and re-introduction of aflibercept-containing chemotherapy and two-stage lung metastasectomies. Case presentation: A 71-years-old yE patient, unfit for intensive oncological treatments owing to Cumulative Illness Rating Scale (CIRS) stage secondary, affected by KRAS c.35 G>T mutant colorectal cancer, rapidly progressing with lung metastases after adjuvant XelOx chemotherapy, reached long-term survival 66 months with no evidence of disease after first-line and re-introduction of tailored, modulated aflibercept (4 mg/kg) d1,15-irinotecan (120 mg/m2) d1,15-5-fluorouracil (750 mg/m2 /day) dd1–4, 15–18; and secondary radical bilateral two-stage lung metastasectomies. Safety profile was characterized by limiting toxicity syndrome at multiple sites (LTS-ms), requiring 5-fluorouracil discontinuation and aflibercept reduction (2 mg/kg), because of G2 hand-foot syndrome (HFS) for >2 weeks, and G3 hypertension. Pharmacogenomic analyses revealed multiple alterations of fluoropyrimidine and irinotecan metabolism: severe deficiency of fluorouracil degradation rate (FUDR), single nucleotide polymorphisms of UGT1A1* 28 variable number of tandem repeats (VNTR) 7R/7R homozygote, ABCB1 c.C3435T, c.C1236T, MTHFR c.C667T homozygote, DPYD c.A166G, TSER 28bp VNTR 2R/3R heterozygote. Conclusions: In clinical practice, a complex management evaluating clinical parameters and RAS/BRAF genotype characterizing an individual patient with MCRC, particularly elderly and/or unfit owing to comorbidities, is required to properly address tailored, multidisciplinary medical and surgical treatment strategies, integrated with careful monitoring of superimposing toxicity syndromes, also related to pharmacogenomic alterations, to gain optimal activity, and long-term efficacy

Interleukin-2 inhalation therapy in renal cell cancer: a case report and review of the literature

Renal cell carcinoma (RCC) is the most common malignancy of the kidney. One third of RCC presents metastatic disease at the time of diagnosis, usually leading to a fatal outcome. Small response rates were seen with most cytotoxic agents including gemcitabine and vinorelbine, whereas systemic therapy with high doses of interleukin 2 (IL-2) has been shown to provide durable complete remissions. However, in consideration of its severe toxicity, IL-2 immunotherapy is restricted to selected patients. Aerosol IL-2 has been introduced as an alternative therapy in cancer patients. However, only very few data are available on its use in patients with pulmonary metastatic RCC. This paper briefly summarizes current clinical experience with the use of inhaled IL-2 therapy, either as a single therapy or in combination with other treatments. In addition, we report on a male patient with pulmonary metastasized RCC who achieved a durable complete response to combined gemcitabine/vinorelbine and interleukin-2 inhalation therapy

Biological effects of a software-controlled voltage pulse generator (PhyBack PBK-2C) on the release of vascular endothelial growth factor (VEGF)

Electrical stimulation (ES) may induce vascular permeability and physiological angiogenesis. ES of rat muscles significantly increases the microvessel density and vascular endothelial growth factor (VEGF) protein levels. Thus, a pilot study was designed to analyze the effects of low-voltage electric impulses on VEGF levels in patients with dystrophic ulcers

Serum sE-selectin levels and carcinoembryonic antigen mRNA-expressing cells in peripheral blood as prognostic factors in colorectal cancer patients

This study analyzed the possible prognostic value of presurgical serum soluble (s)E-selectin levels and/or carcinoembryonic antigen (CEA) mRNA positivity in predicting the disease-free survival of colorectal cancer (CRC) patients

Prognostic value of vascular endothelial growth factor tumor tissue content of colorectal cancer

A longitudinal study was designed to quantify tumor tissue content of vascular endothelial growth factor (VEGF) in patients with colorectal cancer (CRC) and to evaluate its prognostic value in respect to the relapse-free and overall survivals

Somatostatin administration following pancreatoduodenectomy: a case-matched comparison according to surgical technique, body mass index, American Society of Anesthesiologists’ score and Fistula Risk Score

Purpose: This study evaluated the controversial role of somatostatin after pancreatoduodenectomy (PD), stratifying patients for the main risk factors using the most recent postoperative pancreatic fistula (POPF) classification and including only patients who had undergone PD with the same technique of pancreatojejunostomy. Methods: Between November 2010 and February 2020, 218 PD procedures were carried out via personal modified pancreatojejunostomy (mPJ-PD). Somatostatin was routinely administered between 2010 and 2016, while from 2017, 97 mPJ-PD procedures without somatostatin (WS) were performed. The WS group was retrospectively compared with a control (C) group obtained with one-to-one case–control matching according to the body mass index, American Society of Anesthesiologists’ score, and Fistula Risk Score (FRS). Results: A total of 144 patients (72 WS group versus 72 C group) were compared. In the WS group. 6 patients (8.3%) developed clinically relevant POPF, compared with 8 patients (11.1%) in the C group (p = 0.656). In addition, on analyzing the subgroup of high-risk patients according to the FRS, we did not note any significant differences in POPF occurrence. Furthermore, no marked differences in the morbidity or mortality were found. Digestive bleeding and diabetes onset rates were higher in the WS group than in the control group, but not significantly so. Conclusions: The results of the present study confirm no benefit with the routine administration of somatostatin after PD to prevent POPF, even in high-risk patients. However, a possible role in the prevention of postoperative digestive bleeding and diabetes was observed

Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC

Soluble CD40 ligand plasma levels in lung cancer

: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activatio