Specific Neuropeptide Expression in Crohn's Disease Ileocolonic Resection Specimens Is Not Associated with Plexitis at the Ileal Margin or Postoperative Recurrence.

BACKGROUND: Myenteric plexitis is considered a risk factor for postoperative recurrence (POR) in Crohn's disease (CD). The primary purpose of this study was to evaluate the association between neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and substance P (SP) expression and plexitis at the proximal resection margin. The secondary aim was to identify risk factors for POR. METHODS: A retrospective, single-center study on CD patients who underwent ileocolonic resection (ICR) between January 2010 and December 2016 was conducted. The presence and severity of plexitis were evaluated by hematoxylin and eosin stain. Mast cells were highlighted by Giemsa stain. Immunohistochemistry was used to identify T lymphocytes and NPY-, VIP-, and SP-ergic neurons. Neuropeptide expression was quantified using image analysis. RESULTS: Seventy-nine patients were included. No association was detected between NPY, VIP, and SP expression and plexitis. Similarly, the number of involved inflammatory cells, T lymphocytes or mast cells was not correlated with neuropeptide expression. Smoking (hazard ratio [HR] 4.07; 95% confidence interval [CI] 2.08-7.94; p < 0.001), moderate (HR 3.68; 95%CI 1.06-12.73; p = 0.040), and severe myenteric plexitis (HR 7.36; 95%CI 1.12-48.30; p = 0.037) were independent risk factors for endoscopic POR, whereas smoking (HR 2.78; 95%CI 1.01-7.67; p = 0.049), severe myenteric plexitis (HR 20.03; 95%CI 1.09-368.28; p = 0.044), and involved ileal margin (HR 3.45; 95%CI 1.33-8.96; p = 0.011) for clinical POR. CONCLUSIONS: Smoking, moderate or severe myenteric plexitis, and involved ileal margin negatively affect POR in CD patients undergoing ICR. Submucosal and myenteric plexitis at the proximal resection margin is not related to the expression of specific neuropeptides.

Survivin expression in hepatocellular carcinoma. Correlation with clinicopathological characteristics and overall survival.

PURPOSE: Survivin expression is a potential prognostic indicator in various carcinomas. The prognostic value of Survivin for survival in hepatocellular carcinoma, (HCC) however, remains controversial. The aim of the study is to examine the expression of the inhibitor of apoptosis Survivin in HCC and investigate the correlation with the clinic-pathologic characteristics and overall survival (OS) following surgical resection. METHODS: Specimens from patients with resected HCC were examined by Immunohistochemical staining for Survivin and BCL-2expression. Clinical and histopathological data were retrieved from medical and pathology records, while OS was determined by reviewing records from the department of Oncology and personal communication with survivors. Bivariate analysis was performed using the Chi-square and Mann-Whitney U tests, while survival was estimated by Kaplan Meier method and compared with log-rank test. RESULTS: Sixty patients were included in the study. Survivin was expressed in 26 patients (43.3%). Survivin expression was significantly correlated to OS (p=0.014). A statistically significant negative correlation between Survivin and BCL-2 was also noted (p<0.001). CONCLUSIONS: Survivin expression reflects aggressive histological and clinical behavior of HCC and correlates with poorer OS. Further studies are required to confirm if Survivin can be used as a predictive biomarker to evaluate prognosis and target treatments for HCC.

Survivin expression as an independent predictor of overall survival in pancreatic adenocarcinoma.

CONTEXT: Survivin is an antiapoptotic protein with a role in tumorigenesis and suggested prognostic value in several proliferative diseases. AIMS: This study aimed to examine the role of survivin as a prognostic marker in pancreatic adenocarcinoma (PDAC). SETTINGS AND DESIGN: Fifty-one specimens of PDAC were assessed for survivin expression by immunohistochemistry. SUBJECTS AND METHODS: Overall survival and 1-, 3-, and 5-year survival were retrieved retrospectively. STATISTICAL ANALYSIS USED: Bivariate analysis was conducted using Chi-square and Mann-Whitney U tests, while survival analysis was conducted using Kaplan-Meier statistics. RESULTS: Of the 51 assessed cases, 49% were positive for survivin. Survivin expression was significantly correlated 1-year survival and overall survival, particularly in bcl-2 positive cases. CONCLUSIONS: Survivin may be implicated in the bcl-2 and p53 pathways and therefore in the biology of PDAC. Its potential use as a survival predictor and therapeutic target represent a promising field.

Effects of Lornoxicam on Anastomotic Healing: A Randomized, Blinded, Placebo-Control Experimental Study.

Introduction and Aim. With the implementation of multimodal analgesia regimens, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are often administered for optimal pain control and reduction of opioid use. The aim of the study was to examine the effects of lornoxicam, a NSAID, on anastomotic healing employing an animal model. Materials and Methods. A total of 28 Wistar rats were randomly assigned in two groups. All animals underwent ascending colonic transection followed by an end-to-end hand sewn anastomosis. Group 1 received intraperitoneally lornoxicam before and daily after surgery. Group 2 received intraperitoneally an equal volume of placebo. Half of the animals in each group were euthanized on the 3rd pod and the remaining on the 7th pod. Macro- and microscopic indicators of anastomotic healing were compared using a two-tailed Fisher exact test. Results. The lornoxicam group significantly decreased fibroblast in growth and reepithelization of the mucosa at the anastomotic site on the 3rd pod and significantly increased occurrence of deep reaching defects, necrosis, and microabscess on the 7th pod. Conclusion. Lornoxicam administration during the perioperative period adversely affects histologic parameters of intestinal anastomotic healing. These effects of lornoxicam administration were not found to induce significant increase of anastomotic dehiscence in the rat model.

Metallothionein expression in the high-risk carotid atherosclerotic plaque.

OBJECTIVE: Metallothioneins (MTs) are antioxidant proteins expressed in response to injury. We evaluated MT immunoreactivity in carotid plaques obtained from asymptomatic and symptomatic patients. We also assessed the relationship between ultrasonic plaque echodensity, histological grading, computed tomography findings and MT expression. METHODS AND RESULTS: In this ongoing prospective study, patients (n = 123, mean age (+/-SD) 68.4 +/- 7.7 years, 97 men) with high-grade carotid stenosis underwent carotid endarterectomy. Specimens were assessed histologically and immunohistochemically. Echolucent plaques (types 1+2) were more common in symptomatic patients (p < 0.0001) and had more advanced histological lesions (p < 0.0001). Echolucent plaques expressed MTs (in macrophages, fibroblasts and T-lymphocytes) significantly more than echogenic plaques (types 3+4) (all p < 0.0001). MT expression was mainly related to carotid plaque echolucency rather than the presence of symptoms. MT expression was significantly more common in advanced histological lesions. Plaques from asymptomatic or symptomatic patients with abnormal computed tomography findings also showed increased MT expression. There was a time-dependent fall in MT expression after cerebrovascular events (p < or = 0.011). CONCLUSIONS: MT overexpression may be triggered in unstable plaques as a local protective factor. There is a need to identify both causative and protective predictors of the 'vulnerable plaque' in the 'vulnerable patient'. Further studies are needed to resolve these issues.

Ontogeny of intrinsic innervation in the human kidney.

We aimed to define, for the first time, the ontogeny of intrarenal innervation and to assess the distribution and nature of parenchymal nerves in the human fetal kidney. Our material consisted of routinely-processed renal tissue sections from 17 human fetuses, six of 20-24 gestational weeks (gw) and 11 of 25-40 gw, and three adults. We used immunohistochemistry with antibodies to the pan-neural markers neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100, and the adrenergic marker tyrosine hydroxylase (TH). NSE-, NF-, S100-, and PGP9.5-positive nerves, associated with arterial and venous vasculature, were identified in the renal cortex from 20 gw onwards, and their density appeared to increase with gestation, reaching adult levels at 28 gw. Most of the intrarenal nerves were TH-positive. Nerve fibers extended from the corticomedullary region to the outer cortex, reaching the renal capsule in the 3rd trimester. In detail, NSE-, NF-, S100-, PGP9.5-, and TH-immunoreactive fibers were observed in close apposition to the renal artery and its branches, occasionally reaching the afferent and efferent arteriole (3rd trimester). Nerve fibers were detected in close apposition to the juxtaglomerular apparatus in the 2nd and 3rd trimesters. In the renal medulla, NSE-, PGP9.5-, S100-, and TH-positive nerve fibers were detected close to tubular cells as early as 20 gw. However, their density gradually decreased during the 3rd trimester, and they were not observed in the medulla of the adult kidney. In conclusion, the human fetal kidney appears richly innervated during the 2nd and 3rd trimesters. There is a progressive increase in the density of parenchymal nerve fibers towards term from the corticomedullary region to the cortex. Most intrarenal nerves are adrenergic and have a predominant perivascular distribution, implying that renal innervation plays an important functional role during intrauterine life.

Forced swimming differentially affects male and female brain corticosteroid receptors.

Corticosteroid receptors are key mediators of the neuroendocrine response to stress. Previously, we have determined the effects of restraint stress on the regulation of corticosteroid receptor genes in the brain and pituitary of male and female rats. Significant gender- and regional-specific regulation of receptor mRNAs was observed. To further investigate the stressor specificity in the same context, we have determined glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) mRNAs following exposure to swimming stress paradigms applied alone, or in combination with restraint stress. Our data revealed stressor-specific alterations in GR or MR mRNA levels, which were more pronounced in males, the gender most affected by swimming stress. No alterations in GR or MR mRNA levels were detected in the female hippocampus and hypothalamus upon exposure to swimming paradigms, while in males the same stressors down-regulated GR mRNA in the hippocampus (chronic exposure) and up-regulated both genes in the hypothalamus (acute exposure). In the frontal cortex, acute swimming stress caused a reciprocal change in GR mRNA levels in the two sexes. The above difference is not due to circulating ovarian steroids, since ovariectomy did not change the female pattern of GR gene expression following acute stress. Our results further showed a hypothalamic-pituitary-adrenal axis facilitation to a novel superimposed stressor expressed at the level of limbic corticosteroid receptors: When chronically restrained rats of both sexes were exposed to acute swimming stress, a reduced GR/MR mRNA ratio, implying reduced feedback axis sensitivity, was detected in both the hippocampus and the hypothalamus. In conclusion, our work provides additional evidence on stressor, gender and region specificity in the regulation of brain corticosteroid receptors.