The PAS positive material in gastric cancer cells of signet ring type is not mucin.

PURPOSE: The purpose of this study is to assess the exocrine and neuroendocrine properties of tumour cells in diffuse gastric cancer with signet ring cell differentiation. MATERIAL AND METHODS: Mucin mRNA and protein expressions (MUC1, 2, 3, 4, 5AC, 6 and MUC13) were assessed by immunohistochemistry and in situ hybridization. The neuroendocrine properties were evaluated by protein and mRNA expression of the general neuroendocrine markers chromogranin A and synaptophysin. RESULTS: No MUC expression was observed in signet ring tumour cells including the amorphous substance in any of the nine cases. All cases showed immunoreactivity to synaptophysin, and seven out of nine cases immunoreactivity to chromogranin A in signet ring and non-signet ring tumour cells. Chromogranin A mRNA expression was observed in tumour cells in all samples with retained mRNA. CONCLUSIONS: The lack of MUC protein and mRNA in signet ring tumour cells suggests the amorphous substance is not mucin. The lack of MUC mRNA expression in non-signet ring tumour cells questions exocrine differentiation in this tumour group. The abundant protein expression of the general neuroendocrine markers CgA and synaptophysin, and mRNA expression in tumour cells strengthens the hypothesis that this tumour group may be of neuroendocrine origin.

Cytomegalovirus infection and postoperative complications in patients with ulcerative colitis undergoing colectomy.

BACKGROUND: Ulcerative colitis (UC) can be complicated by reactivation of cytomegalovirus (CMV). CMV reactivation may change the course of UC and may require antiviral treatment. Some risk factors of CMV reactivation have previously been identified, whereas the association between CMV reactivation and postoperative complications has not been examined systematically. METHODS: Patients with UC operated with colectomy due to active UC were studied (n = 77). Patient and disease characteristics, as well as postoperative complications were recorded and CMV was detected by immunohistochemical examination of multiple sections from the colectomy specimen. RESULTS: CMV was found in nine (11.7%) colectomy specimens. CMV-positive patients received significantly higher doses of corticosteroids at colectomy than CMV-negative patients (61.1 ± 23 vs 32.5 ± 32 mg/day, p = 0.01). CMV-positive patients were also older, had a higher risk of severe complications, higher American Society of Anesthesiologists (ASA) score, longer preoperative stay, and a higher rate of acute surgery. Complications occurred in 30 (39%) patients after surgery, 8(10.4%) of whom were serious. Two CMV-positive patients (2.6%) died in-hospital after the colectomy. High ASA score was associated with the occurrence of serious complications. CONCLUSION: A relatively small proportion of patients with UC operated by colectomy were CMV positive. CMV positivity was associated with old age, high dose of corticosteroids at operation, high ASA score, acute surgery, and severe postoperative complications. Patients with such characteristics may be at risk of CMV infection and may require special management.

Long-term gastric changes in achlorhydric H(+)/K(+)-ATPase beta subunit deficient mice.

OBJECTIVE: Hypergastrinemia is known to induce enterochromaffin-like (ECL) cell derived tumors in rodents and man. In this study, we have examined the effect of life-long gastric anacidity and secondary hypergastrinemia in H(+)/K(+)-ATPase beta subunit knockout (KO) mice. MATERIAL AND METHODS: Female H(+)/K(+)-ATPase beta subunit KO mice and controls were followed up to 20 months before being sacrificed. At termination, intragastric acidity was measured and internal organs were examined for macroscopic and histological changes. Plasma gastrin and serum albumin were measured. RESULTS: KO mice were anacidic and hypergastrinemic. The oxyntic mucosa was markedly, and with increase in age, hyperplastic with cystic dilatations resembling the changes seen in patients with Menetrier's disease. Serum albumin in KO mice did not differ from controls. KO mice had a marked ECL cell hyperplasia, but only one gastric carcinoma was found. CONCLUSION: H(+)/K(+)-ATPase beta subunit KO mice develop Menetrier-like changes in the stomach, and may be useful in studying the pathogenesis and treatment of Menetrier's disease. The reason why only one KO mice developed gastric neoplasia whereas the histamine-2 blocker loxtidine has previously been found to regularly induce ECL cell carcinoids in mice is not known.

[Frequency of forensic autopsies after deaths in road traffic accidents]. / Frekvens av rettslig obduksjon etter dødsfall i veitrafikkulykker.

BACKGROUND: In 2007, 224 persons died in road traffic accidents in Norway. According to the instruction for prosecution, the police should request forensic autopsy in such deaths. The police's adherence to this instruction varies. The aim of this study was to document enforcement of the instruction for prosecution among police districts in two Norwegian counties (North and South Trøndelag). MATERIAL AND METHOD: Data from forensic autopsies of deaths in road traffic accidents performed at The Department of Pathology and Medical Genetics at St. Olavs Hospital were compared with data from similar deaths in the two counties registered in The Cause of Deaths Statistics in Statistics Norway for the time period 1996-2005. RESULTS: 249 persons died in road traffic accidents in the two counties in the time period assessed; forensic autopsies were performed on 157 (63 %) of them. The forensic autopsy rate decreased from 69 % in the first 5-year period to 57 % in the second period. The largest decrease was in North Trøndelag where the rate dropped from 62 % to 38 %. Drivers of motorized vehicles were to a larger extent autopsied than other road-users; victims of motorcycle accidents were autopsied to a lesser extent than those of car accidents and other types of road traffic accidents. INTERPRETATION: The reduced frequency of autopsy and differences in request practice between police districts may be explained by economical circumstances, different understanding of the importance of forensic autopsies and different interpretation of the instruction for prosecution. It is not known whether there were important differences between those who were autopsied and those who were not.

Histopathologic Features in Relation to Pretreatment Tumor Growth in Patients with Glioblastoma.

BACKGROUND: Rapid growth is a well-known property of glioblastoma (GBM); however, growth rates vary among patients. Mechanisms behind such variation have not been widely studied in human patients. We sought to investigate relationships between histopathologic features and tumor growth estimated from pretreatment magnetic resonance imaging scans. METHODS: In 106 patients with GBM, 2 preoperative T1-weighted magnetic resonance imaging scans obtained at least 14 days apart were segmented to assess tumor growth. A fitted Gompertzian growth curve based on the segmented volumes divided the tumors into 2 groups: faster and slower growth than expected based on the initial tumor volume. Histopathologic features were investigated for associations with these groups, using univariable and multivariable logistic regression analyses. RESULTS: The presence of high cellular density and thromboses was significantly associated with radiologic growth in the multivariable analysis (P = 0.018 and 0.019, respectively), with respective odds ratios of 3.0 (95% confidence interval, 1.2-7.4) and 4.3 (95% confidence interval, 1.3-14.5) for faster growing tumors. CONCLUSIONS: Our findings show that high cellular density and thromboses are significant independent predictors of faster growth in human GBM. This finding underlines the importance of hypercellularity as a criterion in glioma grading. Furthermore, our findings are concordant with hypotheses suggesting hypoxia triggered by thromboses to be relevant for growth of GBM.

A retrospective study of postmortem heart weight in an adult Norwegian population.

The aim of the study is to get a better understanding of what a normal heart weight is and to provide updated reference tables applicable in a Caucasian population. Most previous studies are outdated and often based on other ethnic populations, and these studies are often used in reference tables in pathology textbooks. We included 692 Caucasian subjects, age 20-98years, out of 2834 autopsies performed at the Department of Pathology and Genetics, St. Olavs Hospital-University Hospital of Trondheim between 2003 and 2012. Subjects with various heart or other chronic diseases were excluded. Regression analysis was applied to evaluate the relationship between heart weight and age, gender, body weight, height, body mass index and body surface area. We provide updated reference tables and discuss different approaches to the estimation of heart weight.

Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine, morphine and morphine glucuronides in a series of codeine-related deaths.

This article presents levels and tissue distribution of codeine, codeine-6-glucuronide (C6G), norcodeine, morphine and the morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem blood (peripheral and heart blood), vitreous fluid, muscle, fat and brain tissue in a series of 23 codeine-related fatalities. CYP2D6 genotype is also determined and taken into account. Quantification of codeine, C6G, norcodeine, morphine, M3G and M6G was performed with a validated solid phase extraction LC-MS method. The series comprise 19 deaths (83%) attributed to mixed drug intoxication, 4 deaths (17%) attributed to other causes of death, and no cases of unambiguous monointoxication with codeine. The typical peripheral blood concentration pattern in individual cases was C6G≫codeine≫norcodeine>morphine, and M3G>M6G>morphine. In matrices other than blood, the concentration pattern was similar, although in a less systematic fashion. Measured concentrations were generally lower in matrices other than blood, especially in brain and fat, and in particular for the glucuronides (C6G, M3G and M6G) and, to some extent, morphine. In brain tissue, the presumed active moieties morphine and M6G were both below the LLOQ (0.0080mg/L and 0.058mg/L, respectively) in a majority of cases. In general, there was a large variability in both measured concentrations and calculated blood/tissue concentration ratios. There was also a large variability in calculated ratios of morphine to codeine, C6G to codeine and norcodeine to codeine in all matrices, and CYP2D6 genotype was not a reliable predictor of these ratios. The different blood/tissue concentration ratios showed no systematic relationship with the post-mortem interval. No coherent degradation or formation patterns for codeine, morphine, M3G and M6G were observed upon reanalysis in peripheral blood after storage.

In situ hybridization in human and rodent tissue by the use of a new and simplified method.

In situ hybridization (ISH) is a method that detects and localizes DNA or RNA in morphologically preserved tissue and cell preparations. The method is based on the principle that DNA or RNA will undergo hydrogen binding to complimentary sequences. Selective probes are labeled and used in order to detect specific sequences in tissues or cell preparations. Even though the method has improved over the past decades, there are still issues with sensitivity and specificity. The protocols are nonstandardized, and often time consuming due to multiple steps. In this paper, we have used a new and commercially available ISH kit for the detection of mRNA in formalin-fixed paraffin-embedded tissue. We have used both human and Mongolian gerbil tissue, and we evaluated mRNA expression of the neuroendocrine markers chromogranin A and histidine decarboxylase in both normal tissue and poorly differentiated tumor. In our experience, this method offers excellent sensitivity and specificity. The protocol is more standardized, and our results have been consistent. It is also less time consuming than conventional ISH protocols.

The effects of unilateral truncal vagotomy on gastric carcinogenesis in hypergastrinemic Japanese female cotton rats.

The stomach is innervated by the vagal nerve. Several studies have demonstrated that the vagal nerve has a trophic effect on the rat oxyntic mucosa and that the trophic effect of hypergastrinemia is dependent on intact vagal innervation. The effect of vagal denervation on gastric carcinogenesis has been examined in Mastomys natalensis and hypergastrinemic transgenic INS-GAS mice, with no effect of unilateral vagotomy in Mastomys but an anti-carcinogenic effect in INS-GAS mice. A proportion of female Japanese cotton rats develop spontaneous hypergastrinemia and ECL cell derived gastric carcinomas. In the current study we have examined the effects of unilateral anterior subdiaphragmatic vagotomy on gastric carcinogenesis. Female Japanese cotton rats were operated with unilateral anterior vagotomy or sham-operation at age 2 months and were terminated at age 10 months. Ten of fifteen animals operated by anterior vagotomy and 11 of 16 sham-operated developed hypergastrinemia. Vagotomy did not affect intragastric pH or serum gastrin. When comparing the anterior and posterior sides of the stomachs, vagotomy did not affect the occurrence of dysplasia or carcinoma development in the oxyntic mucosa. However, vagotomy resulted in lower stomach weight and reduced oxyntic mucosal thickness on the anterior side. Vagotomy also resulted in a reduction in volume density of chromogranin A positive cells in the oxyntic mucosa. In conclusion, vagotomy reduced the trophic effects of hypergastrinemia on the ECL cell and oxyntic mucosa, but did not prevent gastric carcinogenesis in female Japanese cotton rats. The effects of vagotomy on gastric carcinogenesis in animal models are conflicting and further studies in patients should be done to clarify the clinically significant effects of vagotomy.

Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting.

OBJECTIVES: Acetylsalicylic acid (ASA) is a cornerstone in the treatment of coronary artery disease (CAD) due to its antiplatelet effect. Cessation of aspirin before coronary artery bypass grafting (CABG) is often recommended to avoid bleeding, but the practice is controversial because it is suggested to worsen the underlying CAD. The aims of the present prospective, randomized study were to assess if ASA administration until the day before CABG decreases the oxidative load through a reduction of inflammation and myocardial damage, compared with patients with preoperative discontinuation of ASA. METHODS: Twenty patients scheduled for CABG were randomly assigned to either routine ASA-treatment (160 mg daily) until the time of surgery (ASA), or to ASA-withdrawal 7 days before surgery (No-ASA). Blood-samples were taken from a radial artery and coronary sinus, during and after surgery and analysed for 8-iso-prostaglandin (PG) F2α; a major F2-isoprostane, high-sensitivity C-reactive protein (hs-CRP), cytokines and troponin T. Left ventricle Tru-Cut biopsies were taken from viable myocardium close to the left anterior descending artery just after connection to cardiopulmonary bypass, and before cardioplegia were established for gene analysis (Illumina HT-12) and immunohistochemistry (CD45). RESULTS: 8-Iso-PGF2α at baseline (t1) were 111 (277) pmol/l and 221 (490) pmol/l for ASA and No-ASA, respectively (P = 0.065). Area under the curve showed a significantly lower level in plasma concentration of 8-iso-PGF2α and hsCRP in the ASA group compared with the No-ASA group with (158 pM vs 297 pM, P = 0.035) and hsCRP (8.4 mg/l vs 10.1 mg/l, P = 0.013). All cytokines increased during surgery, but no significant differences between the two groups were observed. Nine genes (10 transcripts) were found with a false discovery rate (FDR) <0.1 between the ASA and No-ASA groups. CONCLUSIONS: Continued ASA treatment until the time of CABG reduced oxidative and inflammatory responses. Also, a likely beneficial effect upon myocardial injury was noticed. Although none of the genes known to be involved in oxidative stress or inflammation took a different expression in myocardial tissue, the genetic analysis showed interesting differences in the mRNA level. Further research in this field is necessary to understand the role of the genes.