Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of pancreatic ductal adenocarcinoma (PDAC) involves multi-stage development of molecular aberrations affecting signaling pathways that regulate cancer growth and progression. This study was performed to gain a better understanding of the abnormal signaling that occurs in PDAC compared with normal duct epithelia.</p> <p>Methods</p> <p>We performed immunohistochemistry on a tissue microarray of 26 PDAC, 13 normal appearing adjacent pancreatic ductal epithelia, and 12 normal non-PDAC ducts. We compared the levels of 18 signaling proteins including growth factor receptors, tumor suppressors and 13 of their putative downstream phosphorylated (p-) signal transducers in PDAC to those in normal ductal epithelia.</p> <p>Results</p> <p>The overall profiles of signaling protein expression levels, activation states and sub-cellular distribution in PDAC cells were distinguishable from non-neoplastic ductal epithelia. The ERK pathway activation was correlated with high levels of ^S2448p-mTOR (100%, p = 0.05), ^T389p-S6K (100%, p = 0.02 and ^S235/236p-S6 (86%, p = 0.005). Additionally, ^T389p-S6K correlated with ^S727p-STAT3 (86%, p = 0.005). Advanced tumors with lymph node metastasis were characterized by high levels of ^S276p-NFκB (100%, p = 0.05) and ^S9p-GSK3β (100%, p = 0.05). High levels of PKBβ/AKT2, EGFR, as well as nuclear ^T202/Y204p-ERK and ^T180/Y182p-p38 were observed in normal ducts adjacent to PDAC compared with non-cancerous pancreas.</p> <p>Conclusion</p> <p>Multiple signaling proteins are activated in pancreatic duct cell carcinogenesis including those associated with the ERK, PKB/AKT, mTOR and STAT3 pathways. The ERK pathway activation appears also increased in duct epithelia adjacent to carcinoma, suggesting tumor micro-environmental effects.</p

Bacterial translocation in experimental stroke: What happens to the gut barrier?

The reasons of post-stroke infections are still incompletely understood. Bacterial translocation (BT), the passage of viable microbes across an even anatomically intact intestinal barrier, has been described in many critical illnesses. To date, it has not been studied as a source of infection in an animal stroke model. To address this, a permanent left middle cerebral artery occlusion (MCAO) model in rats was used. After 24, 48, and 72 hours (h), sham and experimental groups were sacrificed and samples were taken for BT. Similarity between bacteria detected in tissues (blood, mesenteric lymph node, liver, spleen, and lung) and intestinal microflora was shown with phenotypic methods and antibiotyping. Possible ileum tissue injuries were shown by histopathologic examination (including morphometric analysis). Although there was no bacterial proliferation in the sham groups, 55.5 %, 45.4 %, and 30 % bacterial proliferation was detected in MCAO groups at postoperative hour 24, 48, and 72, respectively. In MCAO groups the bacterial proliferation in tissues and ileum tissue injury scores were higher over time compared to sham groups (p<0.05). Our findings support the view that stroke, itself leads to mucosal damage and bacterial translocation

Abdominal pain in a young man

[No abstract available

Is there any relationship between quality of life and polysomnographically detected sleep parameters/disorders in stable myasthenia gravis?

It is known that quality of life in myasthenia gravis is positively correlated with subjective sleep quality, still no data is available regarding the relationship between QOL and polysomnographically detected sleep parameters and disorders. In this study, we tried to highlighten this relationship, by performing polysomnography. Sleep-related complaints were evaluated in face-to-face interviews with 19 clinically stable MG patients and 26 healthy controls. During the interviews questionnaires assessing sleep quality, excessive daytime sleepiness, fatigue, depression, anxiety, and Turkish version of the MG-QOL 15-item scale [(MG-QOL15(T)] were administered and then an overnight polysomnography was performed. Sleep disorders, especially obstructive sleep apnea and fatigue were higher, whereas subjective sleep duration was significantly lower, in patients than controls. Excessive daytime sleepiness and poor sleep quality were not different between patients and controls. Other than percentage of sleep stage III, which was negatively correlated with MG-QOL15(T) scores, neither other sleep parameters nor sleep disorders were correlated with MG-QOL15(T) scores. MG composite, subjective sleep duration, fatigue severity and Hamilton depression rating scale scores were found to be positively correlated with MG-QOL15(T) scores. It was shown that decreasing disease severity and enhancing psychological well-being will improve patients’ quality of life. We recommend that our findings should be repeated in a large prospective cohort of MG patients. © 2017, Belgian Neurological Society

Inadvertent parathyroidectomy and temporary hypocalcemia: An adverse natural outcome or a true complication during thyroidectomy?

Objective. The aim of this study was to assess the factors that might predict patients at increased risk for inadvertent parathyroidectomy and postoperative symptomatic hypocalcemia during thyroidectomy. Methods. Demographic data as well as the data on preoperative diagnosis, preoperative ultrasonography reports, operation reports, histological findings, and postoperative symptomatic hypocalcemia were collected. A total of 273 (83 male and 190 female patients) thyroid operations were included in this study. Results. Histopathological examination identified inadvertent parathyroidectomy in 10 (3.7%) cases. Statistical analysis identified the presence of cervical lymphadenopathy as detected by preoperative ultrasonography as a risk factor for inadvertent parathyroidectomy. In 57 patients (20.9%) clinically symptomatic postoperative hypocalcemia was observed. However, the difference in the frequency of such hypocalcemia between the patients with and without inadvertent parathyroidectomy was not significant. Statistical evaluation identified total thyroidectomy as a risk factor for postoperative hypocalcemia (p<0.005). Conclusion. Due to our experience, inadvertent parathyroidectomy is not a rare entity during thyroidectomy and the presence of cervical lymphadenopathy, as observed by preoperative ultrasonography, is the only risk factor for inadvertent parathyroidectomy. In contrast, no association between inadvertent parathyroidectomy and postoperative hypocalcemia was detected. Total thyroidectomy was found to be the sole risk factor for symptomatic temporary hypocalcemia

Complications of total thyroidectomy performed by surgical residents versus specialist surgeons

Purpose. Surgeon inexperience has been defined as a significant predictor of deleterious outcome in thyroid surgery; however, the safety of training programs in which residents are the primary surgeons is controversial. The objective of this prospective study was to compare the complication rates of total thyroidectomy (TT) performed by residents with those of TT performed by specialist surgeons in similar patient groups. Methods. Between April 2001 and May 2007, 144 patients underwent TT at our hospital. For 75 operations, the primary surgeon was a resident under the direct supervision of the attending surgeon, and for 69 operations, the primary surgeon was the experienced attending surgeon. Pre-and postoperative vocal cord examinations and serum calcium level evaluations were carried out in all patients. Results. The rates of temporary (unilateral) recurrent laryngeal nerve (RLN) palsy were 2.66% vs 2.17% after TT performed by the residents vs the attending surgeon, respectively. There were no significant differences in the incidences of temporary hypoparathyroidism (20% vs 20.28%), permanent (unilateral) RLN palsy, hematoma, infection, seroma, and incidental parathyroidectomy between the two groups. Conclusion. The complication rates of TT performed by residents and attending surgeons were similar. Thus, residents can perform TT safely and effectively under the direct supervision of a senior surgeon. Ultimately, strict adherence to the contemporary principles of thyroid surgery is of paramount importance. © 2008 Springer

Erythropoietin: A possible cytoprotective cytokine in acute necrotizing pancreatitis

Background/purpose: Despite decades of research and clinical trials, a specific therapeutic treatment for acute pancreatitis (AP) has yet to be developed. The aim of the present study was to investigate the effects of erythropoietin on the severity of taurocolic acid-induced acute necrotizing pancreatitis. Methods: Forty-seven male Wistar albino rats were randomized into seven experimental groups. In group I, animals were sham-operated (n = 5). In groups II, III, IV, IIepo, IIIepo, and IVepo, AP was induced by sodium taurodeoxycholate treatment (n = 7). In groups II, III, and IV, 1 ml normal saline and in groups IIepo, IIIepo, and IVepo, 1000 U/kg body weight erythropoietin (EPO) was administered intramuscularly immediately after the induction of AP. Animals were killed at 24, 48, and 72 h postoperatively. Histopathological and biochemical evaluations were performed. Results: The serum levels of interleukin-6 (IL-6) and tissuelevels of malondialdehyde were found to be significantly lower in EPO-administered groups when compared with the levels in groups without EPO treatment. The severity of pancreatic edema, acinar necrosis, inflammation, and perivascular infiltrate were reduced in all the EPO groups compared with the no-treatment groups. Conclusions: Our findings may reflect the possible cytoprotective effect of EPO in acute necrotizing pancreatitis. © Springer 2009

Does sildenafil reverse the adverse effects of ischemia on ischemic colon anastomosis: Yes, 'no'

Introduction: Sildenafil may lead an improvement in anastomotic healing of ischemic left colon anastomosis. Methods: Thirty-six male Wistar albino rats were randomized into four experimental groups (n = 9 in each group). In group 1, a well-perfused left colonic segment was transected, and free ends were anatomosed. In groups 2, 3 and 4 animals underwent a standardized surgical procedure to induce ischemic left colon anastomosis. Group 2 animals received only tap water. In groups 3 and 4 animals received 10 mg/kg/body-weight and 20 mg/kg/body-weight sildenafil, single dose a day during 4 days, respectively. Rats were sacrificed on day 4 following operation. Anastomotic integrity, intra-peritoneal adhesion scores, anastomotic bursting pressures and tissue hydroxyproline levels were recorded. Histopathological examination of the anastomosis was also performed. Results: There was no statistically significant difference among groups with respect to anastomotic integrity (p = 0.142) but ischemia decreased the anastomotic bursting pressure. The mean bursting pressure values were 78.8 ± 24.1, 43.3 ± 26, 55.1 ± 32.4, and 43.3 ± 20.4 in groups 1, 2, 3, and 4, respectively. Group 1 had the highest values whereas; there was no statistically significant difference between groups 1 and 3. There was no statistically significant difference among groups 2, 3, and 4 with respect to tissue hydroxyproline levels, adhesion scores and the Chiu scores. The highest inflammatory cell presence in the granulation tissue was detected in group 2, whereas the lowest was detected in group 4 (p = 0.0001). The highest fibroblast infiltration in the granulation tissue was detected in group 1 (p = 0.045). Discussion: Our results showed that 10 mg/kg sildenafil decreased the adverse effects of ischemia on the healing of ischemic left colon anastomosis. Additional investigations are needed to confirm the effects of phosphodiesterase-5 inhibitors in ischemic colon anastomosis models. © 2008 Surgical Associates Ltd

Esophageal voice prosthesis mistaken for impacted foreign body

[No abstract available