Usefulness of postmortem biochemistry in forensic pathology: illustrative case reports.

The aim of this work is to present some practical, postmortem biochemistry applications to illustrate the usefulness of this discipline and reassert the importance of carrying out biochemical investigations as an integral part of the autopsy process. Five case reports are presented pertaining to diabetic ketoacidosis in an adult who was not known to suffer from diabetes and in presence of multiple psychotropic substances; fatal flecainide intoxication in a poor metabolizer also presenting an impaired renal function; diabetic ketoacidosis showing severe postmortem changes; primary aldosteronism presented with intracranial hemorrhage and hypothermia showing severe postmortem changes. The cases herein presented can be considered representative examples of the importance of postmortem biochemistry investigations, which may provide significant information useful in determining the cause of death in routine forensic casework or contribute to understanding the pathophysiological mechanisms involved in the death process.

Pancreatic lesions in acute experimental Chagas' disease

BACKGROUND: Chagas' disease is an endemic tropical affliction found from southern United States to Argentina. The acute phase of this disease is difficult to study in man because the symptoms are non-specific and most cases require no medical assistance. Experimental models have been developed for sequential studies, and intense parasitism in all organs and tissues, including the pancreas, have been detected in the acute phase. PURPOSE: To evaluate the involvement of the pancreas in acute experimental Chagas' disease in a mouse model by histopathological characterization. CASUISTIC AND METHODS: Ten BALBc mice, about 20 g, injected i.p. with 100 000 forms of the Y strain of Trypanosoma cruzi were used. The animals were sacrificed after 14 days of infection. Fragments of pancreas were processed by conventional paraffin embedding and hematoxylin-eosin staining. RESULTS: Ruptured pseudocysts and release of parasites to the extracellular medium caused by necrosis of acinar and duct cells and foci of fat were the most striking histopathological features of acute Chagasic pancreatitis. CONCLUSION: Parasitism is the main cause of acute pancreatitis in Chagas' disease.

Laparoscopic resection of uncinate process of the pancreas

Solid pseudopapillary neoplasm of the pancreas is an uncommon but distinctive pancreatic neoplasm with low metastatic potential [1]. Therefore, whenever feasible, an organ-preserving operation should be performed. As previously reported, women with solid pseudopapillary neoplasm of the pancreas may be best treated by more conservative procedures [2]. Recently, laparoscopic pancreatic resections became more common and are being performed in highly specialized centers. There are only six cases of laparoscopic resection for solid pseudopapillary neoplasm of pancreas published in the English literature and, to our knowledge, laparoscopic resection of uncinate process of the pancreas has never been reported [3-6]. This video demonstrates the technical aspects of a totally laparoscopic resection of the uncinate process of the pancreas in a patient with solid pseudopapillary neoplasm. A 26-year-old woman with a 4-cm solid pseudopapillary pancreatic neoplasm was referred for surgical treatment. According to preoperative echoendoscopy, there was a safe margin between neoplasm and main pancreatic duct. The patient was placed in supine position with the surgeon standing between her legs. Four trocars, one 10-mm and three 5-mm, were used. At inspection, the inferior vena cava, transverse colon, duodenum, and pancreas are clearly identified. A Kocher maneuver was performed with complete exposure of pancreatic head and uncinate process. The uncinate process was dissected from the superior mesenteric vein and venous branches were divided between metallic clips or by use of laparoscopic coagulation shears (LCS; Ethicon Endo Surgery Industries, Cincinnati, OH, USA). Blood supply of the duodenum was preserved by ligature of small pancreatic branches from inferior pancreatoduodenal artery. Transection of pancreatic parenchyma was performed using laparoscopic coagulation shears, which is an effective tool for cutting the pancreas [7, 8]. Surgical specimen was removed through a suprapubic incision inside a retrieval bag. A hemostatic absorbable tissue (Surgicel; Ethicon Inc., Cincinnati, OH) was placed in the cutting pancreatic surface, and one round 19F Blake abdominal drain (Ethicon) was left in place. Operative time was 180 minutes and blood loss estimated in 40 ml with no blood transfusion. Hospital stay was 4 days. The patient did not have postoperative pancreatitis or pancreatic leakage, and the abdominal drain was removed on the tenth postoperative day. Final pathology confirmed the diagnosis of solid pseudopapillary neoplasm of pancreas with free surgical margins. The patient was well and asymptomatic 2 months after the procedure. Laparoscopic resection of uncinate process of the pancreas is safe and feasible and should be considered for patients suffering from pancreatic neoplasms.

Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice

Coxsackievirus B3 (CVB3) infection can result in myocarditis, which in turn may lead to a protracted immune response and subsequent dilated cardiomyopathy. Human decay-accelerating factor (DAF), a binding receptor for CVB3, was synthesized as a soluble IgG1-Fc fusion protein (DAF-Fc). In vitro, DAF-Fc was able to inhibit complement activity and block infection by CVB3, although blockade of infection varied widely among strains of CVB3. To determine the effects of DAF-Fc in vivo, 40 adolescent A/J mice were infected with a myopathic strain of CVB3 and given DAF-Fc treatment 3 days before infection, during infection, or 3 days after infection; the mice were compared with virus alone and sham-infected animals. Sections of heart, spleen, kidney, pancreas, and liver were stained with hematoxylin and eosin and submitted to in situ hybridization for both positive-strand and negative-strand viral RNA to determine the extent of myocarditis and viral infection, respectively. Salient histopathologic features, including myocardial lesion area, cell death, calcification and inflammatory cell infiltration, pancreatitis, and hepatitis were scored without knowledge of the experimental groups. DAF-Fc treatment of mice either preceding or concurrent with CVB3 infection resulted in a significant decrease in myocardial lesion area and cell death and a reduction in the presence of viral RNA. All DAF-Fc treatment groups had reduced infectious CVB3 recoverable from the heart after infection. DAF-Fc may be a novel therapeutic agent for active myocarditis and acute dilated cardiomyopathy if given early in the infectious period, although more studies are needed to determine its mechanism and efficacy.

Glucagon-like-peptide-1 receptor expression in normal and diseased human thyroid and pancreas.

Glucagon-like-peptide-1 (GLP1) analogs may induce thyroid or pancreatic diseases in animals, raising questions about their use in diabetic patients. There is, however, controversy regarding expression of GLP1 receptors (GLP1R) in human normal and diseased thyroid and pancreas. Here, 221 human thyroid and pancreas samples were analyzed for GLP1R immunohistochemistry and compared with quantitative in vitro GLP1R autoradiography. Neither normal nor hyperplastic human thyroids containing parafollicular C cells express GLP1R with either method. Papillary thyroid cancer do not, and medullary thyroid carcinomas rarely express GLP1R. Insulin- and somatostatin-producing cells in the normal pancreas express a high density of GLP1R, whereas acinar cells express them in low amounts. Ductal epithelial cells do not express GLP1R. All benign insulinomas express high densities of GLP1R, whereas malignant insulinomas rarely express them. All ductal pancreatic carcinomas are GLP1R negative, whereas 6/20 PanIN 1/2 and 0/12 PanIN 3 express GLP1R. Therefore, normal thyroid, including normal and hyperplastic C cells, or papillary thyroid cancer are not targets for GLP1 analogs in humans. Conversely, all pancreatic insulin- and somatostatin-producing cells are physiological GLP1 targets, as well as most acini. As normal ductal epithelial cells or PanIN 3 or ductal pancreatic carcinomas do not express GLP1R, it seems unlikely that GLP1R is related to neoplastic transformation in pancreas. GLP1R-positive medullary thyroid carcinomas and all benign insulinomas are candidates for in vivo GLP1R targeting.Modern Pathology advance online publication, 12 September 2014; doi:10.1038/modpathol.2014.113.

Hyperplasia to neoplasia sequence of duodenal and pancreatic neuroendocrine diseases and pseudohyperplasia of the PP-cells in the pancreas.

Hyperplastic changes of the neuroendocrine cell system may have the potential to evolve into neoplastic diseases. This is particularly the case in the setting of genetically determined and hereditary neuroendocrine tumor syndromes such as MEN1. The review discusses the MEN1-associated hyperplasia-neoplasia sequence in the development of gastrinomas in the duodenum and glucagon-producing tumors in the pancreas. It also presents other newly described diseases (e.g., glucagon cell adenomatosis and insulinomatosis) in which the tumors are (or most likely) also preceded by islet cell hyperplasia. Finally, the pseudohyperplasia of PP-rich islets in the pancreatic head is defined as a physiologic condition clearly differing from other hyperplastic-neoplastic neuroendocrine diseases.

The Clinical Impact Of Cerebellar Grey Matter Pathology In Multiple Sclerosis.

The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood. To evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients. Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS) and cerebellar functional system (FS) score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT) and the Symbol-Digit Modalities Test (SDMT). Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes. After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001), cerebellar FS (p = 0.002), arm function (p = 0.049), and for leg function (p<0.001). Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013), while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015). Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

The Value Of The 2005 International Society Of Urological Pathology (isup) Modified Gleason Grading System As A Predictor Of Biochemical Recurrence After Radical Prostatectomy.

To compare time and risk to biochemical recurrence (BR) after radical prostatectomy of two chronologically different groups of patients using the standard and the modified Gleason system (MGS). Cohort 1 comprised biopsies of 197 patients graded according to the standard Gleason system (SGS) in the period 1997/2004, and cohort 2, 176 biopsies graded according to the modified system in the period 2005/2011. Time to BR was analyzed with the Kaplan-Meier product-limit analysis and prediction of shorter time to recurrence using univariate and multivariate Cox proportional hazards model. Patients in cohort 2 reflected time-related changes: striking increase in clinical stage T1c, systematic use of extended biopsies, and lower percentage of total length of cancer in millimeter in all cores. The MGS used in cohort 2 showed fewer biopsies with Gleason score ≤ 6 and more biopsies of the intermediate Gleason score 7. Time to BR using the Kaplan-Meier curves showed statistical significance using the MGS in cohort 2, but not the SGS in cohort 1. Only the MGS predicted shorter time to BR on univariate analysis and on multivariate analysis was an independent predictor. The results favor that the 2005 International Society of Urological Pathology modified system is a refinement of the Gleason grading and valuable for contemporary clinical practice.

[renal Tumors: The International Society Of Urologic Pathology (isup) 2012 Consensus Conference Recommendations].

During the last 30 years many advances have been made in kidney tumor pathology. In 1981, 9 entities were recognized in the WHO Classification. In the latest classification of 2004, 50 different types have been recognized. Additional tumor entities have been described since and a wide variety of prognostic parameters have been investigated with variable success; however, much attention has centered upon the importance of features relating to both stage and grade. The International Society of Urological Pathology (ISUP) recommends after consensus conferences the development of reporting guidelines, which have been adopted worldwide ISUP undertook to review all aspects of the pathology of adult renal malignancy through an international consensus conference to be held in 2012. As in the past, participation in this consensus conference was restricted to acknowledged experts in the field.

Transition From Glass To Digital Slide Microscopy In The Teaching Of Oral Pathology In A Brazilian Dental School.

Several medical and dental schools have described their experience in the transition from conventional to digital microscopy in the teaching of general pathology and histology disciplines; however, this transitional process has scarcely been reported in the teaching of oral pathology. Therefore, the objective of the current study is to report the transition from conventional glass slide to virtual microscopy in oral pathology teaching, a unique experience in Latin America. An Aperio ScanScope® scanner was used to digitalize histological slides used in practical lectures of oral pathology. The challenges and benefits observed by the group of Professors from the Piracicaba Dental School (Brazil) are described and a questionnaire to evaluate the students' compliance to this new methodology was applied. An improvement in the classes was described by the Professors who mainly dealt with questions related to pathological changes instead of technical problems; also, a higher interaction with the students was described. The simplicity of the software used and the high quality of the virtual slides, requiring a smaller time to identify microscopic structures, were considered important for a better teaching process. Virtual microscopy used to teach oral pathology represents a useful educational methodology, with an excellent compliance of the dental students.

Chasing Cardiac Physiology And Pathology Down The Camkii Cascade.

Calcium dynamics is central in cardiac physiology, as the key event leading to the excitation-contraction coupling (ECC) and relaxation processes. The primary function of Ca(2+) in the heart is the control of mechanical activity developed by the myofibril contractile apparatus. This key role of Ca(2+) signaling explains the subtle and critical control of important events of ECC and relaxation, such Ca(2+) influx and SR Ca(2+) release and uptake. The multifunctional Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is a signaling molecule that regulates a diverse array of proteins involved not only in ECC and relaxation, but also in cell death, transcriptional activation of hypertrophy, inflammation and arrhythmias. CaMKII activity is triggered by an increase in intracellular Ca(2+) levels. This activity can be sustained, creating molecular memory after the decline in Ca(2+) concentration, by autophosphorylation of the enzyme, as well as by oxidation, glycosylation and nitrosylation at different sites of the regulatory domain of the kinase. CaMKII activity is enhanced in several cardiac diseases, altering the signaling pathways by which CaMKII regulates the different fundamental proteins involved in functional and transcriptional cardiac processes. Dysregulation of these pathways constitutes a central mechanism of various cardiac disease phenomena, like apoptosis and necrosis during ischemia/reperfusion injury, digitalis exposure, post-acidosis and heart failure arrhythmias, or cardiac hypertrophy. Here we summarize significant aspects of the molecular physiology of CaMKII and provide a conceptual framework for understanding the role of the CaMKII cascade on Ca(2+) regulation and dysregulation in cardiac health and disease.

Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation And Ductal Hyperplasia In Non-human Primates.

In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67-positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67-positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67-positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30-positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates.

Robotic Resection of Intraductal Neoplasm of the Pancreas

Background: Minimally invasive techniques have been revolutionary and provide clinical evidence of decreased morbidity and comparable efficacy to traditional open surgery. Computer-assisted surgical devices have recently been approved for general surgical use. Aim: The aim of this study was to report the first known case of pancreatic resection with the use of a computer-assisted, or robotic, surgical device in Latin America. Patient and Methods: A 37-year-old female with a previous history of radical mastectomy for bilateral breast cancer due to a BRCA2 mutation presented with an acute pancreatitis episode. Radiologic investigation disclosed an intraductal pancreatic neoplasm located in the neck of the pancreas with atrophy of the body and tail. The main pancreatic duct was enlarged. The surgical decision was to perform a laparoscopic subtotal pancreatectomy, using the da Vinci (R) robotic system (Intuitive Surgical, Sunnyvale, CA). Five trocars were used. Pancreatic transection was achieved with vascular endoscopic stapler. The surgical specimen was removed without an additional incision. Results: Operative time was 240 minutes. Blood loss was minimal, and the patient did not receive a transfusion. The recovery was uneventful, and the patient was discharged on postoperative day 4. Conclusions: The subtotal laparoscopic pancreatic resection can safely be performed. The da Vinci robotic system allowed for technical refinements of laparoscopic pancreatic resection. Robotic assistance improved the dissection and control of major blood vessels due to three-dimensional visualization of the operative field and instruments with wrist-type end-effectors.

Vascular leakage stimulates phenotype alteration in ocular cells, contributing to the pathology of proliferative vitreoretinopathy

Plasma leaking from damaged retinal blood vessels can have a significant impact on the pathologies of the posterior segment of the eye. Inflammation in the eye and metabolic change resulting from diabetes mellitus causes vascular leakage with alteration of the phenotype of retinal pigment epithelial (RPE) cells and fibrocytes, resulting in changes in cell function. Phenotypically altered cells then significantly contribute to the pathogenesis of retinopathies by being incorporated into tractional membranes in the vitreous, where they secrete matrix molecules, such as fibronectin, and express altered cell surface antigens. We hypothesize that there is a direct relationship between the leaking of plasma and the proliferation and phenotypic change of RPE cells and fibroblasts, thus exacerbating the pathology of retinal disease. If the hypothesis is correct, control of vascular leakage becomes an important target of therapy in proliferative vitreoretinopathy.