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Not only depressed early colorectal cancers but also "small" advanced colorectal cancers (less than 2cm in diameter) have been gradually detected year by year. The latter are thought to be situated between early cancers and "large" advanced cancers and seem to have significant lesions in order to solve a key of "developmental process of colorectal neoplasms". Materials and Methods: From April 1985 to August 1999, 52 small advanced colorectal cancers(less than 2cm in diameter), and 249 submucosal invasive cancers(less than 2cm in diameter), were resected endoscopically and surgically. In terms of the lesions mentioned above, a clinicopathological study was conducted. In this study, all of the lesions were macroscopically classified into three as follows: protruded, flat and depressed types. The depth of submucosal invading carcinomas was divided into three categories: sm1, sm2 and sm3, according to Kudo's classification. Results: Of "small" advanced cancers, 82.7% were depressed type, 16.3% for protruded type and 1.0% for flat type.The degree of cancerous invasion was as follows: depressed type( 42.9% for invasion into the muscularis propria-mp, 57.1% for invasion beyond mp), protruded type( 66.7% for invasion into mp, 33.3% for invasion beyond mp) and flat type (100% for invasion into mp). Average size was as follows: 16.9mm for depressed type, 18.4mm for protruded type and 17.0mm for flat type. On the other hand, of submucosal invasive cancers, 40.3% were depressed type, 54.0% for protruded type and 5.7% for flat type. The rate of degree of cancerous invasion was as follows: depressed type( 40.0% for sm1, 60.0% for sm2,3), protruded type( 57.9% for sm1, 42.1% for sm2,3) and flat type (28.6% for sm1, 71.4% for sm2, 3). Average size was as follows: 10.4mm for depressed type, 13.4mm for protruded type and 15.3mm for flat type. Depressed type of submucosal invasive cancer has a higher rate of massive invasion, in spite of its smaller size, compared with the other types. Moreover, about 80% of "small" advanced cancers are depressed type, which are also invasive. Both of the two cancers mentioned above resemble macroscopically. Conclusion: Most of the small advanced colorectal cancers are thought to be derived of depressed early colorectal cancers because of their tendency toward submucosal invasion and the similarities of morphology.

It has been believed that colorectal cancers evolve from polyps. Recently, however, flat adenomas and depressed carcinomas are also increasingly found not only in Japan but also in Western countries. We can find these depressed lesions only when we noticed their faint redness, therefore, they are not easily found. It is very important to diagnose them because they tend to be deeply invasive even when they are still small. Materials and Method: From April 1985 to June 1999, 15.679 adenomas and early carcinomas in large intestine were resected by endoscopically and /or surgically. These lesions were classified into protruded (8610cases), flat (6692 cases), and depressed (377 cases) types. The zoom colonoscope (CF240Z, CF200Z, Olympus, Tokyo) has been used for this study. Results: The rate of submucosal invasion in protruded lesions were 0% for those less than 5mm' , 1.2% for those 6-10mm', 8.5% for those 11-15mm',16.4% for those 16-20mm and 30.8% for those more than 20mm in diameter. This rates of flat lesions were 0.04%, 0.1%, 1.1%, 8.1% and 25.2% respectively. On the other hand, invasive rates of depressed lesions were 7.4%, in those not exceeding 5mm, 39.4% in those 6-10mm, 63.3% in those 11-15mm, 85.7% in those 16-20mm, and 83.3% in those larger than 20mm. Histopathologically, the depressed lesions consisted of rather straight glands, which showed endophytic growth and penetrated vertically into the deeper layers. When the lesions were invasive, the surface structure was irregular in case the cancer infiltrated massively into the submucosal layer; the surface structure was destroyed and looked nonstructural. Conclusion: Depressed colorectal lesions are different from flat or protruded adenomas in biological behavior, histological construction, and surface structure. Protruded of flat adenomas within 20mm in diameter usually do not invade submucosal layer. However, depressed lesions easily invade submucosal layer even when they are still 5mm or so.Without having the intensity to detect depressed carcinoma we can't find these lesions. If we detect lesions, it is important to analyze pit pattern of them by zooming up and moreover we should decide whether they need to be treated by EMR (Endoscopic Mucosal Resection) or not.

Some flat adenomas spread extensively and circumferentially along the colonic wall although being very short in height compared with the large diameter of more than 10 mm. These large flat adenomas or so-called laterally spreading tumors (LSTs) are sometimes malignant, but not so advanced compared with their large diameter. Despite the large diameter, LSTs are often difficult to find, because they are extremely short and almost normal in color. The keys to detect them are a minimal color change, which is usually faintly red and a slight irregularity of the intestinal wall or interruption of the mucosal capillary network pattern. Dyespraying (usually 0.2-0.4% indigo carmine) helps clarify the margin and the extent of the tumor. [Materials and Methods] From April 1985 to August 1999, 522 LSTs were resected endoscopically and/or surgically. These lesions were classified into granular and non-granular. Endoscopic features of submucosal involvement Duke's A carcinomas in LSTs were analyzed. [Results] Rate of submucosal invasion in LST was 9.2% (48 out of 522). This rate was 9.6% (25 out of 261) in granular type and 8.8% (23 out of 261) in non-granular type. Granular LST consists of many small aggregated nodules. But sometimes it has the remarkable protruding part. Rate of submucosal invasion in Granular LST with the remarkable protruding part was 22.0% (24 out of 109). On the other hand, 68.8% of these 24 submucosal involvement Duke's A carcinomas became invasive in the protruding part exactly. Non-granular LST does not have nodules. Sometimes it has the ill-defined pseudodepression which appears after dye-spraying. This is different from the depressed carcinoma, which has the well-demarcated depression. Rate of submucosal invasion in non-granular LST with the pseudodepression was 18.0% (11 out of 61). All of these 11 submucosal involvement Duke's A carcinomas became invasive in the depressed part. [Conclusion] LSTs are good indication for EMR or endoscopic piecemeal mucosal resection (EPMR). Lesions up to 25 mm in diameter can be removed en bloc by EMR technique. Those over 25 mm would be treated with EPMR method. However, if the part of LST shows coarse protruding structure or psudodepression, the lesion is suspected to be deeply invasive, and therefore should be treated surgically. It is very important to recognize these significant laterally spreading colorectal tumors by careful observation and dye-spraying method.

Alteration in the differentiated state of smooth muscle cells (SMCs) is known to be integral to vascular development and the pathogenesis of vascular disease. However, it is still largely unknown how environmental cues translate into transcriptional control of SMC genes. We found that deltaEF1 is upregulated during SMC differentiation and selectively transactivates the promoters of SMC differentiation marker genes, SM alpha-actin and SM myosin heavy chain (SM-MHC). DeltaEF1 physically interacts with SRF and Smad3, resulting in a synergistic activation of SM alpha-actin promoter. Chromatin immunoprecipitation assays and knockdown experiments showed that deltaEF1 is involved in the control of the SMC differentiation programs induced by TGF-beta signaling. Overexpression of deltaEF1 inhibited neointima formation and promoted SMC differentiation, whereas heterozygous deltaEF1 knockout mice exhibited exaggerated neointima formation. It thus appears deltaEF1 mediates SMC differentiation via interaction with SRF and Smad3 during development and in vascular disease.

Immunoglobulin light chain (AL) amyloidosis has poor long-term prognosis. Sudden cardiac death (SCD) is a common cause of death in patients with cardiac AL amyloidosis. Prophylactic anti-arrhythmic device therapy has been suggested as an option to reduce this risk. We address this issue by reviewing 4 cases of cardiac AL amyloidosis with anti-arrhythmic device therapy. One patient who had an atrioventricular block underwent pacemaker implantation, and the other 3 patients received implantable cardioverter-defibrillator (ICD) implantation for ventricular arrhythmia. All of the 3 ICD implantation cases received appropriate shock therapy for ventricular arrhythmia in the early stage. However, they soon died due to pulseless electrical activity (PEA) or severe heart failure. The median survival period for our 4 cases was as short as 12.3 months. In particular, the 3 patients who required ICD had worse prognoses. Thus, ICD implantation therapy for chemotherapy-resistant cardiac AL amyloidosis may prevent SCD but may not prolong the patient's survival. There are no arguments against pacemaker implantation for cardiac amyloidosis with conduction disturbance; however, the clinical benefit of ICD indication for ventricular tachyarrhythmia is limited. Further extensive clinical research should be performed to definitively determine the effects of ICD implantation on cardiac AL amyloidosis.

Hypertension is the strongest risk factor in cardiac and cerebrovascular diseases among the Japanese. Even daily variations in blood pressure may become a risk, and repeated blood pressure measurement is recommended. Conventional Ambulatory Blood Pressure Monitoring (ABPM), however,may cause discomfort to examinees because they have to have their arms compressed and carry the monitor itself. The number of ABPMmeasurements is limited to about 1 every 15–30 minutes. We therefore attempted, working with medical and engineering teams, to develop a wearable blood pressure sensor that would place less burden on examinees, be less influenced by physical movement, and be usable for continuous blood pressure measurement. We then examined the clinical practicality of the sensor. We modified the existing Moens-Korteweg blood-pressure equation and developed a new systolic blood pressure calculation system that used electrocardiography and ear-lobe pulse waves because the ear lobe would receive little influence from physical movement. We chose three clinical cases from among intensive care unit subjects. We not only estimated their blood pressure using the systemwe developed but also measured arterial pressure directly with an intravascular catheter to see how estimated blood pressure followed actual changes in blood pressure and to evaluate the accuracy of estimated blood pressure. When systolic blood pressure estimated by using the pulse wave velocity method was compared with direct blood pressure measurement, we found that the method captured trends in blood pressure variations correctly. The difference was within ±10 mmHgfor all of the cases. In a comparison using the Bland-Altman method for the three clinical cases, the average difference was –0.4 mmHg, –1.0 mmHg, and –1.7 mmHg and standard deviation was 4.2 mmHg, 4.8 mmHg, and 4.3 mmHg, respectively, which indicated good agreement. Introducing such wearable blood pressure sensors into daily medical practice gets detailed information on continuous blood pressure variation while examinees move freely and the resulting information is used for better quality control of adult diseases. It is also expected that wearable blood pressure sensors can be used in emergency medical cases, in intensive care, and at remote sites.

Little is known about depressive symptoms in heart failure with preserved ejection fraction (HFpEF, EF =50p). We aimed to assess the prevalence of depression, to clarify the impact of depressive symptoms upon clinical outcomes, and to identify factors associated with these symptoms in HF with