After uncomplicated thyroidectomy, decreased upper esophageal pressure may explain both pharyngeal (dysphagia) and laryngeal (vocal impairment) exposure to acid. In the future, proton pump inhibitor therapy protocols should be evaluated.
Although CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIP L (cFLIP L ) and PED/PEA-15, two antiapoptotic proteins whose exogenous expression in normal thyrocytes inhibited the death-inducing signaling complex of CD95. Additionally, small interfering RNA FLIP and PED antisense sensitized thyroid cancer cells to CD95-mediated apoptosis. Exposure of normal thyrocytes to IL-4 and IL-10 potently up-regulated cFLIP and PED/PEA-15, suggesting that these cytokines are responsible for thyroid cancer cell resistance to CD95 stimulation. Moreover, treatment with neutralizing antibodies against IL-4 and IL-10 or exogenous expression of suppressor of cytokine signaling-1 of thyroid cancer cells resulted in cFLIP and PED/PEA-15 downregulation and CD95 sensitization. More importantly, prolonged IL-4 and IL-10 neutralization induced cancer cell growth inhibition and apoptosis, which were prevented by blocking antibodies against CD95 ligand. Altogether, autocrine production of IL-4 and IL-10 neutralizes CD95-generated signals and allows survival and growth of thyroid cancer cells. Thus, IL-4 and IL-10 may represent key targets for the treatment of thyroid cancer. (Cancer Res 2006; 66(3): 1491-9)
BackgroundAbdominal surgery carries significant morbidity and mortality, which is in turn associated with an enormous use of healthcare resources. We describe the clinical course of 30 Intensive Care Unit (ICU) patients who underwent abdominal surgery and showed severe infections caused by Klebsiella pneumoniae sequence type (ST) 258 producing K. pneumoniae carbapenemase (KPC-Kp). The aim was to evaluate risk factors for mortality and the impact of a combination therapy of colistin plus recommended regimen or higher dosage of tigecycline.MethodsA prospective assessment of severe monomicrobial KPC-Kp infections occurring after open abdominal surgery carried out from August 2011 to August 2012 in the same hospital by different surgical teams is presented. Clinical and surgical characteristics, microbiological and surveillance data, factors associated with mortality and treatment regimens were analyzed. A combination regimen of colistin with tigecycline was used. A high dose of tigecycline was administered according to intra-abdominal abscess severity and MICs for tigecycline.ResultsThe mean age of the patients was 56.6 ± 15 and their APACHE score on admission averaged 22.72. Twenty out of 30 patients came from the surgical emergency unit. Fifteen patients showed intra-abdominal abscess, eight anastomotic leakage, four surgical site infection (SSI) and three peritonitis. The overall crude ICU mortality rate was 40% (12 out of 30 patients). Twelve of the 30 patients were started on a combination treatment of high-dose tigecycline and intravenous colistin. A significantly lower mortality rate was observed among those patients compared to patients treated with approved dose of tigecycline plus colistin. No adverse events were reported with high doses of tigecycline.ConclusionsCritically-ill surgical patients are prone to severe post-surgical infectious complications caused by KPC-Kp. Timely microbiological diagnosis and optimizing antibiotic dosing regimens are essential to prevent worse outcomes. Further studies and well-controlled clinical trials are needed to define the optimal treatment of infections by KPC-Kp and, more generally, carbapenem-resistant bacteria.
Background Chronic constipation in children can be caused by cows' milk intolerance (CMI), but its pathogenesis is unknown.Aims To evaluate the histology and manometry pattern in patients with food intolerance-related constipation.Patients and methods Thirty-six consecutive children with chronic constipation were enrolled. All underwent an elimination diet and successive double-blind food challenge. All underwent rectal biopsy and anorectal manometry.Results A total of 14 patients were found to be suffering from CMI and three from multiple food intolerance. They had a normal stool frequency on elimination diet, whereas constipation recurred on food challenge. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, and the number of intra-epithelial lymphocytes and eosinophils. The rectal mucous gel layer showed that the food-intolerant patients had a significantly lower thickness of mucous than the other subjects studied. Manometry showed a higher anal sphincter resting pressure and a lower critical volume in food intolerance patients than in the others suffering from constipation unrelated to food intolerance. Both histology and manometry abnormalities disappeared on the elimination diet.Conclusions Food intolerance-related constipation is characterized by proctitis. Increased anal resting pressure and a reduced mucous gel layer can be considered to be contributory factors in the pathogenesis of constipation. Eur
Introduction Dysphagia and hoarseness are possible complications that can be observed in patients undergoing thyroidectomy or other neck surgery procedures. These complaints are usually related to superior and inferior laryngeal nerves dysfunction, but these can appear even after uncomplicated surgical procedure. Methods We reviewed the current literature available on MEDLINE database, concerning the swallowing disorders appearing after the thyroidectomy. The articles included in the review reported pathophysiology and diagnostic concerns. Results Twenty articles were selected for inclusion in the review. Depends on the possible causes of the difficulty swallowing (related to nerve damage or appearing after uncomplicated thyroidectomy), different types of diagnostic procedures could be used to study patient discomfort, as well as intraoperative nerve monitoring, fiber optic laryngoscopy, endoscopy, pH monitoring, esophageal manometry and videofluorography. Among all these procedures, videofluorography is considered the gold standard to evaluate the entire swallowing process, since that allows a real-time study of all the three phases of swallowing: oral phase, pharyngeal phase and esophageal phase. Conclusion The diagnostic procedures described can help to identify the mechanisms involved in swallowing disorders, with the aim to choose the best therapeutic option. More studies are needed for understanding the causes of the dysphagia appearing after thyroidectomy
Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1alpha, IL-1 ra, interferon-gamma, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed-suction drain was inserted in the wound below the fascia and removed on postoperative day 4. Wound fluid was collected on postoperative days 1-4 and the amount was recorded each time. Growth factors and cytokines production was evaluated as the whole amount produced over a 24-hour period. In all patients, the amount of drain fluid from surgical wounds was more copious the first day after surgery, it decreased significantly afterward. The presence of all cytokines was highest on postoperative day 1, decreasing over the following days. More specifically, the production of IL-1 ra, IL-6, IL-1alpha, and IL-10 on postoperative day 1 fell sharply on postoperative days 3 and 4, whereas, after an initial reduction, interferon-gamma showed an increase from day 2 onward. Vascular endothelial-derived growth factor production increased progressively after the operation reaching statistical significance only on day 4. As for basic fibroblast growth factor, it showed an opposite pattern: it was higher on postoperative day 1 decreasing thereafter. This analysis of cytokine and growth factor production in the drain fluid will lead us to a better evaluation of the events that follow a surgical wound and to a better understanding of the healing process.
Purpose Graves' disease can induce alterations of the psychosocial well-being that negatively influence the overall well-being of patients. Among the current treatments, surgery has limited indications, and its impact on the health-related quality of life has not been well clarified. The aim of this study was to assess the impact of surgery on the quality of life. Methods Fifty-seven patients who underwent total thyroidectomy for Graves' disease in our surgical unit between April 2002 and December 2009 were administered a questionnaire concerning four issues: organic alterations and clinical manifestations, neurovegetative system disturbances, impairment of daily activities, psychosocial problems. Patients were retrospectively questioned after thyroidectomy about the presence of these symptoms in both the pre and postoperative periods. Results There was a significant improvement after surgery in all four areas. Organic manifestations and psychosocial problems had higher average improvements, as did some aspects of the neurovegetative system and difficulties in undertaking daily activities. There were no reports of a worsening of symptoms. Conclusions Surgery resolved the hyperthyroidism in 100 % of cases, and was associated with a quality of life improvement of about 70 % in the patients. Surgery can therefore provide an immediate and effective resolution of Graves' disease, with benefits in health-related quality of life.
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