Acute myocardial infarction caused by a floating thrombus in the ascending aorta: A role of CD34-positive endothelial cells.

A 49-year-old woman was transferred to our hospital with acute-onset chest pain. Her electrocardiogram showed complete atrioventricular block and bradycardia with ST-segment elevation in the inferior leads, and she presented with cardiogenic shock. She was diagnosed with inferior acute myocardial infarction (AMI), and subsequent emergency cardiac catheterization was performed. Selective coronary angiography showed neither stenosis nor obstruction in any of the coronary arteries. Left ventriculography showed a large floating object located on the ascending aortic wall above the ostium of the right coronary artery (RCA). Chest enhanced computed tomography confirmed the floating object in the ascending aorta. These findings suggested that the floating object was associated with the RCA occlusion. To remove the floating object, emergency surgery was performed. The floating object was a large thrombus derived from the localized atheromatous plaque in the ascending aorta. Specialized immunostaining for surface antigen CD34 revealed that regenerated endothelial cells were present on the erosion, along the stalk, and on the floating thrombus. These findings indicate that the CD34-positive endothelial precursor cells strayed into the surface and/or inside of the thrombus, and consequently the floating thrombus supported by these regenerated endothelial cells occluded the RCA, causing AMI. .

A novel role for Niemann-Pick disease type 2C protein in papillae formation.

BACKGROUND: Despite the presence of papillary structures and papillary tumors in humans, the mechanism of papillae formation is unknown. We describe herein a novel role for Niemann-Pick disease type 2C (NPC2) protein, a cholesterol binding protein in the lysosome, in papillae formation. METHODOLOGY/PRINCIPAL FINDING: We examined NPC2 protein expression in surgical samples of papillary tissues by immunohistochemical stain, and all papillary tissues expressed NPC2 protein in the epithelium. To examine our hypothesis of NPC2 protein-mediated papillae formation, we carried out xenograft experiments using wild H460 cells (large cell lung carcinoma cell line) that constitutively expressed abundant NPC2 protein and NPC2 protein-depleted H460 cells by NPC2 shRNA. The xenografts of wild H460 cells and empty shRNA vector cells showed distinct papillae formation, whereas NPC2 protein-depleted H460 cells displayed markedly reduced or no papillae. Since all papillary tissues have open spaces we examined whether NPC2 protein might also contribute to the creation of open spaces. The TUNEL assay in the xenografts of wild and empty shRNA vector H460 cells showed massive cell death, and NPC2 protein-depleted cells displayed minimal cell death. Measurement of caspase 3/7 activities in cultured H460 cells supported NPC2 protein-mediated apoptotic cell death. The presence of excess NPC2 protein, however, did not always produce papillae as seen in the xenografts of CHO cells that were stably transfected with NPC2. CONCLUSIONS/SIGNIFICANCE: The NPC2 protein of certain cells forms papillae coupled with apoptosis that creates open space. This protein may have future applications to modulate papillae formation and papillary growth in tumor tissues.

[Multiple nodular pulmonary amyloidosis complicated with Sjögren syndrome].

A 67-year-old woman, who had been treated for Sjögren syndrome and rheumatoid arthritis for 10 years, was consulted for examination of multiple nodular pulmonary nodules. She has been pointed out multiple pulmonary nodules on chest computed tomography (CT) for 7 years, of which the number and the size gradually increased. When visuting our hospital, approximately 20 nodules up to 10 mm in size were noted. Thoracoscopic resection of the nodule was performed and histological diagnosis was amyloid, which was negative for A- and P- component and positive for transthyretin. Neither amyloid deposition in other organs nor abnormal protein in serum and urine was detected. The diagnosis of localized nodular pulmonary amyloidosis was established. As far as our knowledge, this is the 1st report of transthyretin amyloidosis with Sjögren syndrome.

[Surgical treated pulmonary metastasis from prostatic cancer; report of a case].

A 74-year-old man who had been treated by endocrine therapy for prostatic cancer for 7 years was pointed out an abnormal shadow on the chest X-ray. Computed tomography showed solitary tumor in the lower lobe of the left lung. Transbronchial lung biopsy revealed pulmonary metastasis form prostatic cancer. Because no other metastatic lesions were detected, the patient underwent surgery for pulmonary lesion. The wedge resection of the left lung was performed. Microscopically, the diagnosis of pulmonary and multiple pleural metastases was established. The pulmonary metastasis without bone nor lymph node metastasis is rare. Pleural metastasis should be considered in case of pulmonary metastasis from prostatic cancer. Surgical indication for pulmonary metastasis from prostatic cancer has to be decided carefully.

Immunohistochemical study on liver fibrosis in biliary atresia.

BACKGROUND/AIMS: Although advanced liver fibrosis is a critical complication in influencing the outcome of biliary atresia (BA), the mechanism is poorly understood. In adult hepatic disorders, the relationships between sinusoidal liver cells (SLC) such as hepatic stellate cells (HSCs), some growth factors and enzymes concerned with extracellular matrix (ECM) metabolism have been clarified, but are unknown in BA. This study aimed to investigate such relationships in BA. METHODOLOGY: Seventeen liver samples from 14 patients with BA were immunohistochemically examined using primary antibodies such as alpha smooth muscle actin (alphaSMA), transforming growth factor beta (TGFbeta), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP)-1, MMP-2, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. The degree of liver fibrosis and these immunohistochemical findings were compared and examined semiquantitatively. Ultrathin sections from two samples were also examined with electron microscopy. RESULTS: The immunoreactivity of alphaSMA and MMPs increased with the degree of liver fibrosis, whereas that of TGFbeta, PDGF, and TIMPs showed no difference in expression in groups with any degrees of fibrosis. The immunoreactivity of MMPs statistically significantly increased in fibrotic livers. Electronmicroscopically, HSCs had many filaments in their cytoplasm, showing myofibroblastic morphology. CONCLUSIONS: The present study gave a different result than other reports on adult liver fibrosis. Livers with BA may be in a predominant state of fibrolysis, indicating the presence of the similar process to recovery from liver fibrosis in adults.

Small adenocarcinoma of the lung: prognostic significance of central fibrosis chiefly because of its association with angiogenesis and lymphangiogenesis.

To clarify the reason why central fibrosis (CF) is an important histological prognostic factor in small adenocarcinoma (SA) of the lung, tumor tissues from 50 patients with SA < or = 2 cm in diameter were investigated using immunohistochemical and in situ hybridization analysis for factors relating to extracellular matrix and vessels. CF was observed in 33/50 cases (66%). In adenocarcinoma areas, positive activity was observed with both primary antibodies and probes for matrix metalloproteinase-2 (MMP-2) in 11/50 patients (22%), membrane-type 1 matrix metalloproteinase (MT1-MMP) in 39/50 patients (78%) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 49/50 patients (98%). In CF areas, the positive activity of fibroblastic cells was seen for only TIMP-2 in 32/33 patients (97%). In CF areas, both CD34-positive (blood and lymphatic) vessels and D2-40-positive lymphatic vessels were semiquantitatively increased in 16/33 patients (48.5%) by immunohistochemistry. Tumors with increased vessel density were associated with statistically lower disease-free survival curves compared with tumors without increased vessels. Lymphatic vessels in some CF showed intravasation by carcinoma cells. In conclusion, CF could be an important histological prognostic factor in SA chiefly because of its association with angiogenesis and lymphangiogenesis.

Heterotopic gastrointestinal mucosa and pancreatic tissue in a retroperitoneal tumor.

We believe that this is the first report of a retroperitoneal tumor consisting of heterotopic gastrointestinal mucosa and pancreatic tissue. The patient was a 19-year-old woman with the chief complaint being occasional back pain. Abdominal computerized tomography demonstrated a 3.1 x 2.5 x 3.2-cm low-density solid and cystic lesion adjoining the left renal vein between the aorta and inferior vena cava. Angiography revealed that the inferior vena cava was displaced by the hypovascular tumor. The retroperitoneal lesion was diagnosed preoperatively as a benign tumor such as a neurogenic neoplasm or lymphangioma. At laparotomy, a cystic tumor was found, which existed behind the inferior vena cava and renal vessels, and contained reddish-brown fluid, suggesting hemorrhage in the past. The cut surface of the tumor showed a unilocular cyst with partially hypertrophic wall. Histopathological examination revealed a cystic tumor lined with heterotopic gastric and duodenal mucosa, with pancreatic tissue in the muscularis propria. In addition, evidence of bleeding from the gastric mucosa was observed in the cystic tumor. External secretion from these tissues could have triggered the hemorrhage and expanded the tumor, possibly resulting in the back pain.

Impaired longitudinal conduction in crista terminalis is necessary for sustenance of experimental atrial flutter.

Sustained atrial flutter (AFL) can be induced by creating a lesion between the vena cava in dogs. In previous studies on this model, the crista terminalis (CT) was often injured, and thus, role of CT in sustained reentry was not well understood. We hypothesized that impaired longitudinal conduction in CT is necessary for sustained AFL. In 16 anesthetized, open-chest dogs, linear radiofrequency ablation of the intercaval region was performed without interrupting CT. Intra-atrial conduction times (IAT) along CT were measured using a plaque electrode (25x35 mm) containing 30 bipolar electrodes before and after additional ablation of CT (group A, n=10) or the pectinate muscle (PM) region (group B, n=6). In group A, IAT along CT was 27 +/- 5 ms at baseline and was increased to 43 +/- 3 ms after ablation of CT (P<0.001). In group B, IAT along CT was 28 +/- 4 ms at baseline and 27 +/- 3 ms after ablation of PM (P=NS). Sustained AFL lasting >20 minutes was induced in 10/10 dogs in group A only after additional ablation of CT, and in 0/6 dogs in group B (P<0.001). The cycle lengths of AFL after ablation of the intercaval region and additional ablation of CT were 119 +/- 14 and 140 +/- 14 ms, respectively (P<0.01). There was a significant positive correlation between the cycle length of AFL and IAT along CT (r2=0.63, P<0.001). These results indicate that longitudinal conduction property in CT and not in PM strongly affects sustenance of AFL in this model.

A multihormonal pituitary adenoma with growth hormone and adrenocorticotropic hormone production, causing acromegaly and Cushing disease.

Pituitary adenoma with growth hormone (GH) and corticotropin (ACTH) production causing apparent acromegaly and Cushing disease is extremely rare. A 45-year-old woman had a pituitary macroadenoma and severe insulin resistance. Physical examination showed a fully developed acromegaly associated with mild Cushingoid features. Serum GH, insulin-like growth factor-I, ACTH, and cortisol levels were all elevated. Hormonal loading tests resulted in GH levels increasing paradoxically in response to thyrotropin-releasing hormone (TRH), but not corticotropin-releasing hormone (CRH). A similar unexpected increase in ACTH and cortisol levels occurred in response to TRH and GH-releasing hormone. After trans-sphenoidal resection of the pituitary macroadenoma immunohistochemistry revealed the presence of either diffuse but faintly GH-positive cells or sparse but distinct ACTH-stained cells. A marked amelioration of insulin resistance was observed postoperatively. The elevated ACTH and cortisol levels should therefore be investigated by CRH and dexamethasone suppression tests for the coexistence of Cushing disease to exclude the possibility of underlying ACTH-producing tumors.

Relationship between postoperative recurrence and expression of cyclin E, p27, and Ki-67 in non-small cell lung cancer without lymph node metastases.

BACKGROUND: Cyclin E and p27 play pivotal roles in cancer development and progression. We investigated whether the prognosis in cases of non-small cell lung cancer without lymph node metastases that underwent complete resection could be associated with tissue expression of cyclin E, p27, and Ki-67. METHODS: Tumors from 62 patients at least 5 years after surgery were assessed by immunohistochemistry for expression of cyclin E, p27, and Ki-67. Disease-free survival (DFS) after surgery was used to evaluate disease prognosis. We also investigated the relationship between expression of these factors and postoperative recurrence. RESULTS: In non-small cell lung cancer, p27-negative expression and pT factor were significantly unfavorable prognostic factors in multivariate analysis. The DFS rate in cyclin E-positive expression was significantly lower than in cyclin E-negative expression. Similarly, p27-negative expression and high Ki-67 expression correlated with a shortened DFS rate. In combinations of expression of cyclin E and p27, the cyclin E-negative/p27-positive group had a significantly higher DFS rate than did the other groups. According to histological type, there were correlations between the risk of postoperative recurrence and expression of these three biological factors, especially in adenocarcinoma. CONCLUSION: By analyzing the expression of cyclin E, p27, and Ki-67 of tumor cells, it was possible to extract the patient group for whom closer follow-up and postoperative treatment is necessary to improve survival rate.

Adenoma of the nipple in an adolescent.

We recently treated a 14-year-old girl with a clinically and histologically diagnosed with adenoma of the nipple. Enucleation of a mass preserving the nipple was successfully performed. Adenoma of the nipple is a rare disease which is often mistaken clinically for Paget's disease. About 200 cases of the tumors have been reported worldwide so far. The most common symptom is erosion of the nipple and nipple discharge. Our case had erosion of the nipple but no discharge. Adenoma of the nipple is a benign lesion which can be successfully treated by a simple surgery.

A case of macroprolactinoma with subclinical growth hormone production.

We describe a rare case of macroprolactinoma with subclinically synchronous growth hormone (GH) production. A 59-year-old man with a giant adenoma in his pituitary had elevated serum prolactin (PRL) and insulin-like growth factor (IGF)-I levels, despite normal levels of basal GH. Serum GH levels were paradoxically increased in response to an intravenous administration of thyrotropin-releasing hormone (TRH). Prolonged exposure to glucose as a result of oral glucose tolerance testing (oGTT) failed to decrease GH levels. Two-week treatment with cabergoline, a dopamine D2 receptor agonist, decreased serum PRL and GH levels, and size of the tumor. Immunohistochemistry and in situ hybridization revealed PRL-producing cells capable of synchronous GH production. Acidophilic stem cell adenoma may be responsible for these phenomena. The nature of high proliferation and invasive tumor growth should be kept in mind when managing patients with this cell type of adenoma. IGF-I levels should be followed in PRLoma, even when basal GH levels are within the normal range, because mixed PRL- and GH-producing tumors would lie underneath. Further endocrinological examinations such as TRH test and oGTT are recommended when elevated IGF-I levels are detected.