Fatal Left Ventricular Free Wall Rupture Complicating Acute Myopericarditis.

This is a case of a 59-year-old man presenting with myopericarditis. Over a 2-week period, he developed progressive symptoms and worsening pericardial effusion, leading to cardiac tamponade. Pericardiocentesis revealed hemopericardium, and multidetector computed tomography angiography showed left ventricular free wall rupture. The patient collapsed abruptly, and autopsy confirmed the findings.

Immunohistochemical Study of Adhesion Molecules in Irritable Bowel Syndrome: A Comparison to Inflammatory Bowel Diseases.

BACKGROUND: The surface of endothelial cells is covered with cell adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) that mediate the adhesion and extravasation of leukocytes and play a pivotal role in inflammatory response. The aim of this study was to investigate the role of expression of adhesion molecules in inflammatory bowel disease (IBD) patients, irritable bowel syndrome (IBS) patients, and normal colonic mucosa. MATERIALS AND METHODS: IBS and IBD patients along with normal colonic mucosa were recruited in the study. In all groups, two biopsies were taken from each of the three anatomical sites (terminal ileum, cecum, and rectum). Three monoclonal antibodies, E-selectin mAb, VCAM-1 mAb, and ICAM-1 mAb, were applied for immunohistochemical analysis. RESULTS: In IBD patients, the expression of intensity of E-selectin, VCAM-1, and ICAM-1 was found decreased, at least in cecum and rectum, in comparison with IBS patients and controls (P < 0.001, P < 0.005, and P < 0.007, respectively). Comparison of the expression of intensity of the aforementioned molecules in IBS patients and controls revealed significant augmentation at the cecum and rectum of IBS patients. CONCLUSIONS: The expression of adhesion molecules appeared lower in IBD patients compared to IBS patients and controls. In addition, the expression of adhesion molecules appeared higher in IBS compared to the control group. Therefore, it could be hypothesized that the expression of adhesion molecules could be considered as an early event in the process of proinflammatory IBS group and may be other factors play a crucial role in the process of intestinal inflammation in IBD patients.

Expression of orexin-A (hypocretin-A) in the hypothalamus after traumatic brain injury: A postmortem evaluation.

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity. The key component of TBI pathophysiology is traumatic axonal injury (TAI), commonly referred to as diffuse axonal injury (DAI). Coma is a serious complication which can occur following traumatic brain injury (TBI). Recently, studies have shown that the central orexinergic/ hypocretinergic system exhibit prominent arousal promoting actions. Therefore, the purpose of this study is to investigate by immunohistochemistry the expression of beta-amyloid precursor protein (ß-APP) in white matter of parasagittal region, corpus callosum and brainstem and the expression of orexin-A (ORXA) in the hypothalamus after traumatic brain injury. RESULTS: DAI was found in 26 (53.06%) cases, assessed with ß-APP immunohistochemical staining in parasagittal white matter, corpus callosum and brainstem. Orexin-A immunoreactivity in hypothalamus was completely absent in 5 (10.2%) of the cases; moderate reduction of ORXA was observed in 9 (18.4%) of the cases; and severe reduction was observed in 7 (14.3%) of the cases. A statistically significant correlation was found between ß-APP immunostaining in white matter, corpus callosum and brainstem in relation to survival time (p < 0.002, p < 0.003 and p < 0.005 respectively). A statistically positive correlation was noted between ORX-A immunoreactivity in hypothalamus to survival time (p < 0.003). An inverse correlation was noted between the expression of ß-APP in the regions of brain studied to the expression of ORX-A in the hypothalamus of the cases studied (p < 0.005). CONCLUSIONS: The present study demonstrated by immunohistochemistry that reduction of orexin-A neurons in the hypothalamus, involved in coma status and arousal, enhanced the immunoexpression of ß-APP in parasagital white matter, corpus callosum and brainstem.

Unusual abscess masquerading as poorly differentiated adenocarcinoma of the colon showing characteristics of choriocarcinoma.

Extragonadal non-gestational choriocarcinoma (ENC) is an uncommon malignant tumor occasionally found in the gastrointestinal tract. ENC is characterized by a biphasic tumor growth with distinct areas of adenocarcinoma and choriocarcinoma differentiation. Primary choriocarcinoma of the colon is extremely rare, with only 21 cases reported in the literature. Most of the perforation of colorectal cancers occurs in the abdominal cavity, while abdominal wall abscess is rare; the psoas abscess associated with colon carcinoma is even less observed. Herein, we report the case of a 61-year-old female with poorly differentiated adenocarcinoma of the ascending colon and sigmoid, with choriocarcinomatous differentiation, masquerading a psoas abscess formation. Unfortunately, despite the aggressive therapy, the patient's disease rapidly progressed, and she died within 2 months after the diagnosis. The typical morphological pattern, immunohistochemistry, and its correlation with serum ß-human chorionic gonadotropin enabled a correct diagnosis.

Proinflammatory cytokines in irritable bowel syndrome: a comparison with inflammatory bowel disease.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a common disease often considered as a functional intestinal disorder. Inflammation in IBS is a quite intriguing theory. The aim of this study was to investigate tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 expression in inflammatory bowel disease (IBD) patients, IBS patients and normal controls. METHODS: IBS and IBD patients along with normal controls were recruited in the study. In all groups, 2 pinch biopsies were taken at each of 3 anatomical sites (terminal ileum, cecum, and rectum). IBS patients were also subcategorized according to the syndrome clinical manifestations. Two monoclonal antibodies (mAb), TNF-α mAb and IL-6 mAb, and one polyclonal antibody IL-1ß mAb were applied for immunohistochemical analysis. RESULTS: In IBD patients intensity of TNF-α and IL-1ß were lower than in IBS patients or controls, while IL-6 was significantly increased comparing to the aforementioned groups. In IBS patients TNF-α was increased comparing to IBD patients or controls, while IL-6 and IL-1ß were similar to controls. In IBS subgroups, TNF-α was lower in diarrhea predominant IBS patients and higher constipation predominant IBS patients. Differences among IBS subgroups regarding IL-6 and IL-1ß were nonsignificant. CONCLUSIONS: IL-6 seems to be the most important proinflammatory cytokine in IBD patients, while TNF-α could play a more significant role in IBS pathogenesis.

Unusual abscess masquerading as poorly differentiated adenocarcinoma of the colon showing characteristics of choriocarcinoma

Extragonadal non-gestational choriocarcinoma (ENC) is an uncommon malignant tumor occasionally found in the gastrointestinal tract. ENC is characterized by a biphasic tumor growth with distinct areas of adenocarcinoma and choriocarcinoma differentiation. Primary choriocarcinoma of the colon is extremely rare, with only 21 cases reported in the literature. Most of the perforation of colorectal cancers occurs in the abdominal cavity, while abdominal wall abscess is rare; the psoas abscess associated with colon carcinoma is even less observed. Herein, we report the case of a 61-year-old female with poorly differentiated adenocarcinoma of the ascending colon and sigmoid, with choriocarcinomatous differentiation, masquerading a psoas abscess formation. Unfortunately, despite the aggressive therapy, the patient's disease rapidly progressed, and she died within 2 months after the diagnosis. The typical morphological pattern, immunohistochemistry, and its correlation with serum β-human chorionic gonadotropin enabled a correct diagnosis.

Giant Metastatic Liver Tumor of Unknown Primary Origin: Thoracic Autopsy Solves the Mystery.

A 59-year-old male patient was hospitalized in the Internal Medicine Department for investigation of hepatic metastases from an unknown primary neoplasm. During the hospitalization the patient died from acute myocardial infarction. The autopsy revealed a 8.2 kilograms (kg) liver that was diffusely infiltrated by whitish metastatic masses. No other tumor was detected, apart from a 2.5 centimeters (cm) pulmonary nodule next to the right intermediate bronchus that was histologically compatible with small cell lung cancer (SCLC). Despite the fact that hepatic metastases from SCLCs are common, diffuse metastatic hepatomegaly from a malignant pulmonary nodule are rarely seen. Given that the most common cause of malignancy-related death is lung cancer, early diagnosis and appropriate management of pulmonary nodules is of paramount importance.

Syndecan-1, Epithelial-Mesenchymal Transition Markers (E-cadherin/ß-catenin) and Neoangiogenesis-related Proteins (PCAM-1 and Endoglin) in Colorectal Cancer.

The Syndecan-1 protein plays a crucial role in cell proliferation, cell adhesion, cell migration and angiogenesis and, at the same time, its co-expression with E-cadherin is regulated during epithelial-mesenchymal transition (EMT). In colorectal cancer (CRC), the expression of syndecan-1, E-cadherin/ß-catenin complex is frequently disturbed. Angiogenesis is critical for the growth and metastatic spread of tumors. In the present study, we focused on the expression of these biological molecules and their prognostic significance in human CRC. Formalin-fixed paraffin-embedded surgical specimens from 69 patients with CRC were immunostained for syndecan-1, E-cadherin, ß-catenin, endoglin (CD105) and CD31 (platelet cell adhesion molecule (PCAM-1)). A significant association was found between syndecan-1 with E-cadherin (p<0.0001), as well with ß-catenin (p<0.0001). High ß-catenin expression appeared to reduce the risk of poor outcome. Endoglin microvascular density (MVD) count was correlated significantly with Dukes' stage (p<0.0001), vessel invasion (p<0.0001), lymph node metastasis (p=0.039), liver metastasis (p<0.0001), recurrence of disease (p=0.010) and poor survival rate (p<0.0001). Endoglin tumor epithelial cell expression was associated with E-cadherin, ß-catenin and syndecan-1 (p=0.001, p=0.068 and p=0.005, respectively). In conclusion, changes in the pattern of expression of syndecan-1, EMT markers, E-cadherin/ß-catenin, in association with endoglin (CD105), may be involved in tumor progression and prognosis of CRC patients. Further studies are needed to clarify the interaction between these proteins and tumor initiation and progression.

Predictive role of thymidine phosphorylase expression in patients with colorectal cancer and its association with angiogenesis-related proteins and extracellular matrix components.

BACKGROUND: Thymidine phosphorylase (TYMP) is an angiogenic factor that has potent chemotactic activity for endothelial cells and is involved in 5-fluorouracil (5-FU) metabolism. In colorectal cancer (CRC), previous studies evaluating the relationship between TYMP expression and clinicopathological features have yielded inconsistent results. The aim of this study was to investigate the prognostic value of TYMP, its association with other angiogenic factors, proliferation markers and, to our knowledge, for the first time its relationship with extracellular matrix components. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens from 97 patients with CRC were immunostained for TYMP, vascular endothelial growth factor (VEGF), microvascular density (CD34), proliferation marker (Ki-67), proliferating cell nuclear antigen (PCNA), p53 oncoprotein and extracellular matrix components (collagen type IV, fibronectin, tenascin and laminin). Survival curves were calculated with the Kaplan-Meier method. RESULTS: Immunoreactivity was observed in the cytoplasm (cyt) and nucleus (n) of the tumor cells, as well in the stroma (st), endothelium and tumor-associated macrophages. High TYMPcyt expression was observed in 7.2% of the cases, moderate in 22.7% and weak in 59.9%, while 10.3% were negative. High TYMPst expression was observed in 58.8% of the cases. TYMPcyt expression was correlated with the VEGF expression of tumor cells and VEGF expression of vessels (p=0.014 and p=0.022, respectively). TYMPst expression was correlated with VEGF expression and tenascin (p=0.014 and p=0.011, respectively). Patients with higher TYMPcyt expression had a more favorable overall survival (p=0.041) in univariate analysis compared to patients without TYMP expression. CONCLUSION: These findings suggest that TYMP plays an important role in angiogenesis, extracellular matrix remodeling and in the prognosis of patients with CRC, but further studies are needed to clearly define its role in CRC.

Association of syndecan-1 with angiogenesis-related markers, extracellular matrix components, and clinicopathological features in colorectal carcinoma.

Syndecan-1 is a transmembrane heparansulfate proteoglycan, which regulates cell proliferation, migration, angiogenesis, cell-to-cell and cell-to-extracellular matrix adhesion and may influence malignant cell behavior. We investigated the alterations of syndecan-1 expression in colorectal cancer and analyzed the relationship between clinicopathological parameters, proliferation indices, angiogenic markers, and extracellular matrix components. Syndecan-1 protein expression observed in the tumorous epithelium was high in 52/97 (53.6%) of the studied cases, moderate in 20/97 (20.6%), and weak in 5/97 (5.22%) of the cases, and there was strong stromal expression in 34.02% of the tumors. Syndecan-1 expression was statistically correlated to VEGF expression in tumor (p=0.001) and vessels (p=0.007). In addition, there was a borderline correlation between syndecan-1 expression and tenascin (p=0.053). Patients with weak staining reaction had a more unfavorable prognosis (p=0.032) in univariate analysis. These results indicate the implication of syndecan-1 in the remodeling and angiogenesis of colorectal cancer tissue, through interaction with other extracellular matrix components and VEGF, probably influencing the tumor progression and aggressiveness.

Altered expression of cell cycle and apoptotic proteins in human liver pathologies.

Τhe expression of cell cycle (P53, Ki-67, P21, and P27) and apoptotic proteins (BCL-2 and BAX) was investigated by immunohistochemistry in paraffin-embedded formalin-fixed tissues of normal and pathologic liver. An increased frequency of expression of P21 in cirrhosis and hepatocellular carcinoma (HCC) (p=0.003 and p=0.001 respectively) was found; P27 protein expression was more frequent in hepatitis (p=0.001) and HCC (p=0.003) when compared with normal tissue. BCL-2 protein was markedly more frequent in steatohepatitis (p<0.05) as compared to normal liver, in hepatitis cases (p=0.002) and in metastases (p<0.033). The expression of BAX was more frequent in hepatitis (p=0.001) and cirrhosis (p<0.001). We demonstrated in our study the expression of these proteins at different levels in liver pathologies. These findings have implications for understanding the evolution from liver inflammation to cirrhosis and associated carcinogenesis.

Comparison of the dysadherin and E-cadherin expression in primary lung cancer and metastatic sites.

Dysadherin, a cancer associated cell membrane glycoprotein, has been reported to downregulate E-cadherin. Aberrant expression of E-cadherin has been associated with the development of metastases in patients with cancer. Even though the expression of dysadherin and E-cadherin has been studied in primary non-small cell lung carcinoma, little is known about its expression at the distant metastases sites. We investigate by immunohistochemistry the relationship between E-cadherin and dysadherin in 111 cases of primary lung carcinomas (53 squamous cell carcinomas, 21 adenocarcinomas, 13 large cell carcinomas, and 24 small cell carcinomas), and their distant metastases. The intensity, the expression pattern and the percentage of neoplastic cell staining were recorded and the results were correlated with clinicopathological findings of the subjects. Dysadherin immunostain was expressed in 61 (54.95%) of the cases, and increased dysadherin expression was significantly correlated with tumour size (p=0.003), distant metastases (p=0.0034), and metastasis size (p=0.0008). Reduced E-cadherin expression was noted in 46 (41.45%) of the cases, and was correlated with high-grade tumour (p=0.02), infiltrative growth pattern (p=0.042), and advanced stage (p=0.032). Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. In lung carcinomas dysadherin expression seems to reflect tumour aggressiveness and may be considered a positive marker of poor prognosis when considered alone or/and in combination with down-regulation of E-cadherin.

Fatal poisoning in the region of Epirus, Greece, during the period 1998-2004.

The aim of this study was to assess the characteristics of acute poisoning deaths in the deprived region of Epirus, north-west Greece, as they were recorded among the autopsies performed at the Department of Forensic Medicine and Toxicology, Medical School, University of Ioannina, Greece. A retrospective study of the forensic records and the toxicological data of all autopsies performed over the period 1998-2004 revealed that 46 cases (2.9%) out of the 1582 total autopsies performed were attributed to acute fatal poisoning. The age range was from 16 to 94 years (mean+/-SD=46.20+/-22.13). Substances of abuse were implicated in 22 cases (47.8%), pesticides in 9 cases (19.6%), gases in eight cases (17.4%), corrosives in 4 cases (8.7%), and prescription drugs in 3 cases (6.5%). There were 35 males (76.1%) and 11 females (23.9%) and the age range was 16-94 years (mean+/-SD=39.26+/-19.00) and 16-93 years (mean+/-SD=63.36+/-23.46) for males and females, respectively. Fourteen out of the 46 fatal poisonings were suicide (30.4%), 30 (69.6%) were accident, and 2 were uncertain cases. Pesticides were the most common poisons used for suicide purposes (64.3% of suicides). Drugs of abuse were implicated in the majority of accidental poisoning deaths (73.3%) and were recorded mainly for males (95.5%). The selected cases were classified according to ICD-9 codes.

Sudden death due to primary intracranial neoplasms. A forensic autopsy study.

Although most fatal tumors are diagnosed well before a patient's death, occasionally forensic pathologists encounter cases in which the presence of a primary tumor of the central nervous system had not been suspected prior to death. A search for cases of sudden death due to intracranial tumors from a total of 1985 autopsies from the archives of the Department of Forensic Pathology, University of Ioannina, Greece, in the period 1998-2005, was undertaken. Two such cases in which a medico-legal autopsy had disclosed brain tumors were found. The first case was a 34-year-old man who had been found unconscious in bed, and died a few hours after hospitalization. His autopsy had revealed a 7-cm glioblastoma at the level of the third ventricle. The second case involved a 67-year-old man presenting with brain tumor, diagnosed 1.5 months previously. The patient had died after 16 hours of hospitalization. A 4-cm astrocytoma of the left temporal lobe had been found at autopsy. In both cases, the tumors may, directly or indirectly, have been the underlying cause of death. The importance of a thorough neuropathological examination in all cases of sudden death, in which no extracerebral cause had been found, is emphasized.

Giant lipoma: an unusual cause of intrathoracic mass.

Postmortem examination performed in a 39-year-old woman revealed a well-circumscribed, round, large mass in the right hemithorax. The tumor was attached with its pedicle to the ventral pericardium and adjoined the diaphragm with compression of the right lower lobe of the lung. Histologic examination confirmed the diagnosis of giant lipoma.

Trends in suicide mortality in the deprived region of Epirus (north-west Greece) during the period 1998-2002.

This study determines the risk factors associated with suicide rates and the investigation of time trends in the deprived region of Epirus, north-west Greece, which is considered to be one of the least developed prefectures of the EU. Data selected demonstrated: (1) a mean age-standardized suicide rate per year of 4.00/100,000 for males, 1.29/100,000 for females and 2.65/100,000 for the total population; (2) a significant rising trend of male suicides in the 35-44 and 65-74 age groups; (3) a low female suicide rate in < 35 years age group and a relatively stable rate in the other age groups; (4) a significantly higher suicide rate in men than in women from both urban and rural areas and in older men from rural areas; (5) higher rates of suicide among widowed men and unmarried women; (6) the use of predominantly violent suicide methods, especially self-shooting, hanging and drowning; (7) a significant peak in the total suicide rate in the spring and summer months and a decreased rate in September; and (8) three out of four of the suicide victims had consumed alcohol and/or other drugs before the act. Data reported here shows some remarkable trends compared to previous reports on suicide in Greece and other countries, probably due to cultural and life style characteristics of the study population.

Churg-Strauss syndrome (allergic granulomatous angiitis) associated with T lymphoblastic lymphoma.

We report a rare case of Churg-Strauss syndrome in a 37-year-old man, presented as ileus intestinal and associated with Tlymphoblastic lymphoma, that was located in the retroperitoneal space and infiltrated the suprarenal gland. The T lymphoblasts, with the immunohistochemical method, disclosed positivity for CD3 and CD8, while they were negative for Pan B and CD20.

Fatal poisoning from ingestion of Datura stramonium seeds.

A 19-y old male who intentionally ingested an unknown quantity of Datura stramonium seeds to experience its hallucinogenic effects was found dead. Hyoscyamine and scopolamine were detected in postmortem blood and urine. Blood concentrations of hyoscyamine and scopolamine were 1.1 and 0.2 microg/mL, respectively; in urine only hyoscyamine at 14.2 microg/mL was found. This fatality presents the highest blood concentrations ever reported and confirms that death was due to Datura Stramonium seed ingestion.

Immunohistochemical analysis of expression of bcl-2 protein in papillary carcinomas and papillary microcarcinomas of the thyroid gland.

AIM: To compare the expression of anti-apoptotic protein bcl-2 and tissue proliferation Ki-67 antigen in tissues of human papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC). METHODS: Bcl-2 protein expression in PTC and PTMC has been evaluated by immunohistochemical analysis. RESULTS: Bcl-2 protein was observed in normal thyroid gland in all the cases; in 25% of the cases of papillary carcinomas the immunoreaction was strong and in 75% of the cases--moderate. In 25% of the cases of papillary microcarcinomas the bcl-2 expression was totally negative and 35% was moderate. Bcl-2 expression was lower in non-sclerosing non-encapsulated (NSNE) (25%) cases of PMCs than in non-sclerosing encapsulated (NSE) (57.15%) cases of PTMCs (p < 0.05). MIB-1/Ki-67 expression was notably reduced or not expressed in normal and benign thyroid tissue. MIB-1 immunoreactivity was present in papillary carcinoma, and on a lower level--in PTMCs. The MIB-1 labelling index of NSE and sclerosing non-encapsulated (SNE) cases was lower than that in NSNE (p < 0.005). CONCLUSION: The present study indicated that NSNE cases of PTMCs may be an early stage in tumor progression, and the bcl-2 and MIB-1 immunohistochemistry may be a valuable tool in predicting the malignant behavior in PMTCs, and contributes to the understanding the growth characteristics of papillary carcinomas of the thyroid gland.

Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the oncogene c-erbB-2, sex steroid hormone receptors and other clinicopathological features, in normal, hyperplastic and neoplastic endometrium.

The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death, that involves an intrinsic normal cell death program. Bcl-2 overexpression was originally described in a follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. Variation in the frequency of apoptosis in hormone-sensitive tissues, such as the endometrium, is known to occur as a result of hormonal changes in both physiological and pathological circumstances. In this study we examined bcl-2 protein expression in a total of 170 samples of endometrial tissues (18 proliferative endometrium, 14 secretory endometrium, 35 adenomatous hyperplasia and 103 carcinomas). The results were compared with p53, pRb and c-erbB-2 proteins expression, estrogen and progesterone receptors status, with the proliferative activity and with clinicopathological features. The expression of bcl-2 protein was lower in the group of carcinomas, when compared with the cases of adenomatous hyperplasia (p < 0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.07). In normal proliferative endometrium bcl-2 expression was correlated with PCNA (p = 0.026) and in secretory endometrium it was correlated with ER status (p = 0.042). In hyperplasias, bcl-2 was correlated with PCNA (p = 0.019) and the PR (p = 0.007) expression. In carcinomas, decreased bcl-2 expression was associated with increased tumor grade (p = 0.04). A positive relationship between bcl-2 expression and pRb, as well as PCNA score (p = 0.014 and p = 0.001, respectively), was also found. These results indicate that bcl-2 expression may play a role in the inhibition of apoptosis in endometrial carcinoma and its expression seems to be associated with tumor differentiation and cell proliferation.