Protection of ischemic myocardium has been attempted by a variety of pharmaceutical and non-pharmaceutical methods. When the coronary intervention is not indicated by some reasons in patients with ischemic heart failure, medical treatments are expected to offer cardioprotection against the persistence of stenotic/occlusive lesions of the epicardial coronary artery. The pharmaceuticals such as the angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta blocker, Ca antagonist, ATP-sensitive K channel opener and statin, or nonpharmaceutical approaches such as physical exercise, cardiac resynchronization, ventricular assist devices, and preconditioning upon ischemic insults appear to improve myocardial endothelial nitric oxide (NO) synthase (eNOS) function. Such eNOS activation contributes to amelioration of the cardiac dysfunction and remodeling induced by myocardial ischemia. Therefore, based on clinical evidence and basic research on clinical demand, we postulate a concept of ‘myocardial endothelial NO activator' from the standpoint of mechanistic insights beyond the class-effects of each pharmaceutical category and each non-pharmaceutical intervention. In addition to such continuous eNOS activation for treating chronic ischemic heart failure, rapid eNOS activation in the setting of acute ischemic events upon chronic myocardial ischemia by new strategies such as postconditioning seems to be also essential for developing further effective anti-heart-failure therapies.

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Papillary carcinoma and follicular carcinoma are types of differentiated thyroid carcinomas, develop from the same thyroid follicular epithelial cells and show distinct biological behavior. Although several studies have demonstrated differences in the biological characteristics of these carcinomas, little is known about the genetic backgrounds that underlie these differences. The clarification of the genetic background can lead to the understanding of thyroid carcinogenesis, proper therapeutic strategies, and development of the molecular targeting drugs. Recently, aberrant activation of RAS-RAF-MEK-MAP kinase signaling pathway is frequently found in thyroid carcinoma. The pathway transmits a mitogenic signal to the nucleus, and constitutive activation of the pathway is thought to promote uncontrolled cell division. In our series, BRAF mutation was detected exclusively in papillary carcinoma (54%), and was exclusively V599E (a single nucleotide change of A-T at nucleotide 1796). NRAS mutation was observed in follicular carcinoma (50%) and in anaplastic carcinoma (28%), and was exclusively Q61R (a single nucleotide change of A-G at nucleotide 182). No mutations were found in KRAS or HRAS.
In this chapter, we explain the role of RAS-RAF-MEK-MAP kinase pathway in carcinogenesis of the thyroid and its clinical implication based on our study. In addition, we review the current knowledge in this field.

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Occurrence of a primary or metastatic angiosarcoma in the oral cavity is extremely rare. The term gepithelioid angiosarcomah (EA) has been used to designate a morphological variant of angiosarcoma characterized by poorly differentiated epithelial- like cells arranged in carcinoma-like fashion, but which still forms identifiable vascular channels. To our knowledge, EA in the oral region is extremely rare. Only two previous instances of EA in the maxilla have been reported. We present an additional oral case of EA in a 71-year-old man. Histology of the initial oral biopsy revealed suspicion of un- differentiated carcinoma. In order to confirm the diagnosis, immunohistochemical examinations were performed. The final diagnosis was EA. The patient died of multiple metastases shortly after the final diagnosis, implying an aggressive clinical course. This case showed that it was essential to use the vascular markers, such as FVIIIRag and CD34, for a correct histological diagnosis of EA. The oral EA described here almost certainly represents a metastatic focus, rather than the primary site of tumor origin. This is because clinical history of EAs appears to arise in deep, rather than in more superficial tissues.

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We report a 72-year-old man who was admitted to our department with multiple nodules of hepatocellular carcinoma (HCC) in a cirrhotic liver because of HCV infection. Unlike most of the nodules, one in segment 2 (S2) showed hypoattenuation on computed tomography (CT) during hepatic arteriography (CTA), and hyperattenuation on CT during arterial portography (CTAP). Fine needle aspiration biopsy of the nodule established the .diagnosis of hepatic adenomatous hyperplasia.
Why the S2 nodule showed hyperattenuation on CT AP is not clear. Two possibilities are considered: i) greater portal blood flow into the nodule than into the surrounding cirrhotic parenchyma, ii) existence of a period during the course of hepatocarcinogenesis when the portal blood flow into the nodule is higher in density on CTAP.

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We diagnosed colonic cancer using low serum ferritin levels as a clue in two patients with cardiac or cardiopulmonary disease. In the course of the follow up, the serum ferritin levels decreased to less than 18 ng/mL without significant appearance of iron-deficiency anemia. One patient showed positive immunological fecal occult blood test results whereas the other not. Both patients rejected further colonoscopy because of their concern for stress in relation to their cardiac or cardiopulmonary diseases, but instead agreed to positron emission computed tomography (PET) using a F-18 deoxyglucose at their own expense. In both patients, PET documented abnormal tracer accumulation in the colon. From the results of PET imaging, they eventually agreed to colonoscopy. A colonic adenocarcinoma was detected at the site of the positive PET finding in each patient. Both patients underwent curative resection of the cancer. The detection of the levels of serum ferritin may be available for the screening colonic cancer in patients declining colonoscopic examination.

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Primary squamous cell carcinoma of the breast is a rare entity. We treated a 55-year old woman who came to us with bleeding from the left breast tumor. The tumor was 7×8×10 cm in size with ulceration and surgical biopsy results showed it to be squamous cell carcinoma of the breast, while metastatic work-up findings ruled out other sources of primary tumor. She also complained of nausea and vomiting, and brain CT disclosed cerebellar metastasis. The metastatic brain tumor was surgically removed, however, the symptoms became gradually exacerbated. The patient died 67 days after admission.

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