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Background: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands., Methods: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution., Results: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins., Conclusions: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins., (© 2023 American Cancer Society.) more...

Dysbiosis of the microbiome on the airway mucosa leads to the development of chronic inflammatory and allergic disorders. The aim of this study was to consider the potential diagnostic criteria for allergic fungal rhinosinusitis (AFRS) and nonallergic fungal rhinosinusitis (FRS), and the role of fungal presence in an environment for the development of AFRS. In this study, 136 patients were divided into two groups: patients with positive specific immunoglobulin E (sIgE) and fungal finding (AFRS group), and patients with negative sIgE and positive fungal finding (FRS group). The study design included: anamnesis data, sIgE, eosinophil count and skin-prick test, rhinology and computerized tomography (CT) observation and mycological finding. Our results showed: (i) the prevalence in Serbia is: AFRS 1.3%, FRS 2.8%; (ii) 30.4% patients with sIgE+ had more often severe and recurrent chronic rhinosinusitis (CRS) (P = .005) and the presence of polyps (P = .025); (iii) 46.4% patients with sIgE+ had positive fungi on the sinonasal mucosa and were considered as AFRS; (iv) patients with AFRS had more frequent asthma (P = .024) and chronicity of CRS >10 years (P = .000). The persistent fungal presence and prolonged duration of CRS could be a silent threat for the progression of inflammation and development of FRS. Lavage with hypertonic-NaCl should be included in the everyday hygiene routine in an effort to decrease fungal load and antigenic exposure. The presence of allergological parameters and better response to corticosteroid therapy in AFRS patients should be considered as crucial diagnostic criteria for AFRS., (© The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...

Background: The microvascular anastomosis remains a technically sensitive and critical determinant of success in free tissue transfer. The microvascular anastomotic coupling device is an elegant, friction-fit ring pin device that is becoming more widely used., Objective: To systematically review the literature to examine the utility of the microvascular coupler in free tissue transfer., Methods: A comprehensive database search was performed to identify eligible publications. Inclusion criteria were anastomotic coupler utilization and free-tissue transfer. Recorded information from eligible studies included patient age, follow-up, radiation history, number of free-flaps and failure rates, reconstruction subsites, number of coupled venous and arterial anastomoses, coupling time, conversion to sutured anastomosis, coupler size and thrombosis rates., Results: Twenty-five studies reporting on 3207 patients were included in the analysis. A total of 3576 free-flaps were performed within the following subsites: 1103 head and neck, 2094 breast, 300 limb or body, and 79 nonspecified. There were only 26 reported flap failures (0.7%). A total of 3497 venous and 342 arterial coupled anastomoses were performed. The primary outcome measure was thrombosis rates, and there were 61 venous (1.7%) and 12 arterial (3.6%) thromboses reported. Mean coupling time was 5 min, and 30 anastomoses (0.8%) were converted to suture., Conclusion: Flap survival and revision-free application of the microvascular coupler occurred in more than 99% of cases. There is a substantial time savings with coupler use. Venous and arterial thrombosis rates are comparable with the best results achieved by sutured anastomosis and, when used by experienced surgeons, the coupler achieves superior results. more...

Background: A disintegrin and metalloproteinase (ADAMs) have been associated with multiple malignancies. ADAMs are involved in cell fusion, cell migration, membrane protein shedding and proteolysis. ADAM8 has been found to be overexpressed in squamous cell carcinomas of the lung. A new study showed that ADAM8 is significantly overexpressed in metastasis of squamous cell carcinomas of the head and neck (HNSCC)., Methods: We determined ADAM8 levels in the serum of 79 HNSCC patients at the time of diagnosis, in 35 patients 3 months after treatment and in 10 patients 1 year after therapy and compared the results to the sera of 31 healthy volunteers. We also constructed tissue microarrays to detect ADAM8 immunohistochemically in 100 patients. The results were correlated with the survival data of the patients to determine the diagnostic and prognostic value., Results: The data demonstrated that patients with high ADAM8 expression in the tumor have worse survival rates. We found that high ADAM8 serum levels correlated with high ADAM8 expression in tumor samples. Soluble ADAM8 levels did not show any prognostic or diagnostic properties., Conclusion: In summary ADAM8 expression is a prognostic factor for survival of patients with head and neck squamous cell carcinoma. more...

Background/aims: RCAS-1 is a transmembrane protein that is involved in the evasion of host immune surveillance by tumor cells. It has been found to be a valuable prognostic and diagnostic marker in a number of different malignancies. The objective of the study was to analyze the potency of RCAS-1 as a biomarker in the serum of patients with head and neck squamous cell carcinoma (HNSCC)., Methods: ELISA was performed with prospectively collected serum samples from 60 patients with HNSCC (taken at the time of diagnosis, after 3 and 12 months) and from 31 healthy controls. To correlate serum levels with RCAS-1 expression in the tumor, immunohistochemical staining of RCAS-1 was done using a tissue microarray., Results: Surprisingly, median sRCAS-1 levels were basically identical between tumor patients and controls. Interestingly, patients with low RCAS-1 values at the time of diagnosis had better disease-free survival. 62% of tumor samples expressed RCAS-1 but we could not demonstrate a correlation between protein expression and serum levels., Conclusion: This study was the first to correlate RCAS-1 levels in the serum and in the tumor of the same patients. RCAS-1 seems to have prognostic properties although larger studies will be necessary to fully evaluate its role in HNSCC., ((c) 2010 S. Karger AG, Basel.) more...

Objective: Metastasis to the jaw is a rare finding in pancreatic cancer; only five cases of tumor spread to the oral region have been described., Case Report: We report on a previously healthy 54-year-old man who attended the hospital in 2006 because of a mandibular mass. Histology was positive for adenocarcinoma and computed tomography led to the diagnosis of pancreatic cancer. Chemoradiotherapy was started but had to be stopped early because of intraoral bleeding from the metastasis. The patient subsequently received palliative chemotherapy. The primary cancer was stabilized but the mandibular mass progressed despite cytostatic therapy. Despite best supportive measures the patient died nine months after presentation., Conclusion: In making the decision on whether metastasectomy should be performed in an uncommon site of metastatic spread such as the mandibula, both the possibility of cure and also the potentially decreased response to conservative therapy and the patient's decreased quality of life have to be considered. more...

Cancer is among the leading causes of morbidity and mortality in the Western world. Despite recent advances, most therapeutic approaches fail to eradicate the entire neoplastic clone. The remaining cells often develop metastasis and/or recurrences and therefore may represent attractive targets of therapy. A new exciting concept in this regard suggests that each neoplasm represents a heterogeneous population of cells that pertain to long-term tumor growth both in vivo in the natural host and in experimental animals. This concept postulates the existence of small fractions of 'tumor stem cells' that exhibit a capacity for self-renewal and unlimited growth and therefore are distinct from their progeny. Based on these hypotheses, the targeting of neoplastic stem cells is considered indispensable for eradication of the entire clone and for the development of curative treatment approaches. However, tumor stem cells often may be quiescent cells and may express a different profile of targets compared with 'more mature' tumor cells. Therefore, current efforts have attempted to characterize target expression profiles in cancer stem cells in various malignancies. In the this review, the authors have provided a brief summary of the current knowledge of neoplastic stem cells and the application of respective concepts in translational oncology with the ultimate objective of improving anticancer therapy. more...

The analytical challenges of Pt determination by ICP-SFMS posed by different human tissues and fluids have been critically assessed. Investigated samples were (1) urine, (2) serum of cancer patients sampled during chemotherapy with carboplatin, (3) microdialysates (20 micro L sample volume) collected from tumor and non-tumor tissue, and, finally-for the first time-(4) human lung tissue to study background concentrations of inhaled platinum. Sample preparation involved microwave digestion and open vessel treatment or simple dilution (microdialysates). Depending on the sample preparation and introduction systems used (microconcentric nebulization, ultrasonic nebulization with and without membrane desolvation) excellent procedural detection limits (3s criterion) of 0.35 pg g(-1) for urine, 420 pg g(-1) for serum, 400 pg g(-1) for lung tissue and 13 pg g(-1) for microdialysates could be obtained. Ultratrace concentrations of 1-40 pg g(-1), and 1000-3000 pg g(-1) were measured in urine and human lung tissue, respectively, as typical for samples in environmental studies. Quantification was carried out by IDMS and standard addition in the case of urine samples. Internal standardization could not correct for non-spectral interferences in external calibration. In the serum and microdialysates of patients during chemotherapy with carboplatin, elevated Pt levels ranging between 0.01 and 10 micro g g(-1) were determined by external calibration ((195)Pt isotope). For all investigated samples spectral interferences could be excluded by following different strategies. High-resolution control measurements ((194)Pt, (195)Pt) were performed in the case of elevated Pt levels, i.e. for microdialysates and serum samples. An Hf/Pt ratio of 0.4 was determined in human lung samples. An HfO formation ratio of 0.2% was assessed for standard solutions at the present experimental conditions, revealing that the contribution of (179)Hf(16)O, (178)Hf(17)O, (177)Hf(18)O to the (195)Pt isotope signal used for quantification was not significant. more...

To characterize the potential of ciprofloxacin penetration into human soft tissues following intravenous (i.v.) and oral (p.o.) administration, we measured the free ciprofloxacin concentrations in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue by microdialysis. In addition, ciprofloxacin concentrations were measured in cantharis-induced skin blisters, saliva, and capillary plasma and were compared to the total concentrations in venous plasma. Furthermore, a pharmacodynamic in vitro model was used to simulate in vivo pharmacokinetics in bacterial culture. Eight healthy volunteers received ciprofloxacin in an open randomized crossover fashion either as a single i.v. infusion of 400 mg over 60 min or as a single p.o. dose of 500 mg. For both tissues the mean areas under the concentration-time curves (AUCs) for interstitial space fluid (AUC(interstitial fluid)s) were significantly lower than the corresponding AUC(plasma)s, with AUC(interstitial fluid)/AUC(plasma) ratios ranging from 0.38 to 0.68. For skeletal muscle, the AUC(interstitial fluid) was significantly higher after administration of 400 mg i.v. than after administration of 500 mg p.o., with a ratio of the AUC after p.o. administration/AUC after i.v. administration of 0.64. The ratio of the concentration in skeletal muscle/concentration in plasma increased over the entire observation period, implying that ciprofloxacin concentrations were not at steady state. The ratio of the concentration in skin blister fluid/concentration in plasma reached values above 4, indicating a preferential penetration of ciprofloxacin into inflamed lesions. The concentrations in saliva and capillary blood were similar to the corresponding total levels in plasma. In vitro both in vivo ciprofloxacin concentration-time profiles were equally effective against select bacterial strains. In conclusion, single-dose administration of two bioequivalent dosage forms of ciprofloxacin might lead to differences in target site pharmacokinetics. These differences, however, are not related to a difference in target site pharmacodynamics. more...

Microdialysis is a widely used experimental technique, which offers the opportunity to measure drug and metabolite concentrations in the interstitial space fluid in animals and humans. However, microdialysis probes need to be calibrated in vivo to obtain a recovery factor, which describes the relative drug transfer across the membrane. Recently, novel time-saving calibration techniques, based on the use of reference compounds, have been developed. In particular, the use of endogenous urea levels has been advocated. In the present study we set out to validate the use of the urea reference technique for microdialysis probe calibration in healthy volunteers, employing glucose and paracetamol as model analytes. Urea calibration was compared with the results of two standard calibration techniques, i.e. the no net flux technique and the retrodialysis technique. For glucose, recovery values, calculated by the urea reference technique differed significantly from those values, which were assessed by the no net flux technique (p < 0.05), whereas for paracetamol recovery values did not differ significantly, albeit a high intramethod variability was observed (CV=66%). As a conclusion, we could not confirm the hypothesis that recovery values calculated by the urea reference technique provide equivalent results compared with standard calibration techniques. more...

Background: Recent data indicate a higher level of effectivity of beta-lactam antibiotics if serum concentrations are kept above the minimal inhibitory concentration (MIC) of the pathogen. This concept would favor continuous infusion over bolus dosing. However, it is usually not the serum concentration but the free interstitial concentration in the target tissue that determines antibiotic activity. We therefore set out to measure effective drug concentrations in the interstitial space of muscle and subcutaneous adipose tissue and to compare trough levels and times above the MIC after bolus versus continuous infusion of cefpirome., Methods: Twelve healthy volunteers received a single dose of 2 g cefpirome as an intravenous bolus or as a continuous infusion over 8 hours in a crossover design, and the resulting free interstitial tissue concentrations were measured with use of microdialysis., Results: After bolus injection, mean interstitial trough concentrations were 3.0 +/- 1.9 microg/mL and 2.1 +/-1.0 microg/mL for muscle and subcutaneous tissue, respectively; continuous infusion resulted in trough levels of 10.1 +/- 6.8 microg/mL and 10.1 +/- 4.6 microg/mL for muscle and subcutaneous tissue, respectively. This resulted in significantly longer times above the MIC with continuous infusion for Staphylococcus epidermidis and Enterobacter cloacae. Bacteria with an MIC < or =1 would be covered by either method, whereas higher doses seem to be necessary for Pseudomonas aeruginosa., Conclusion: Although susceptible organisms will usually be covered sufficiently with standard dosing regimens, soft tissue infections with bacteria that have MIC values of 2 to 8 may profit from continuous application. Coverage of P aeruginosa, however, would be inadequate with conventional daily doses of 4 g cefpirome regardless of the method of application. more...