Radical surgery with mini-thoracolaparotomy for esophageal cancer

In our institute, radical esophagectomy through mini-thoracolaparotomy has been performed as a less-invasive surgery for esophageal cancer since 1996. We describe the indications for and operative procedures of mini-thoracolaparotomy. Next we report the preliminary results of a prospective randomized trial that compared mini-thoracolaparotomy with conventional thoracolaparotomy in 30 patients without neoadjuvant therapy. There were no differences between the two groups in operative time, bleeding volume, and number of dissected lymph nodes. Thoracolaparotomy was effective in decreasing the quantity of morphinerequired in the ICU and shortening hospitalization after surgery. Thoracolaparotomy was effective in preventing a decrease in and early recovery of postoperative vital capacity. In clinical data on radical esophagectomy performed through a right thoracotomy and reconstruction with a stomach tube from 1996 to 2000, the 5-year survival rate of 63 patients in the thoracolaparotomy group (67.6%) did not differ from that of 124 patients in the conventional surgery group (49.9%).     

Drug discovery based on microarray

Gene regulatory networks developed from full genome expression libraries from gene perturbation variant cell lines can be used to quickly and efficiently identify the molecular mechanism of action of drugs or lead compound molecules. We developed an extensive yeast gene expression library consisting of full-genome cDNA array data for over 500 yeast strains each with a single gene disruption. Using this data, combined with dose and time course expression experiments with the oral antifungal agent, we used Boolean network discovery techniques to determine the genes whose expression was most profoundly affected by this drug. Our system identified the gene as the most significantly suppressed target molecule due to exposure to the antifungal agent. This process for network based drug discovery can significantly decrease the time and resources necessary to make rational drug targeting decisions.     

Death in epilepsy with special attention to suicide cases

To examine clinical features of cases of death among epilepsy patients as a case-control study, with special attention to suicide, we analyzed the records of 43 deceased patients with well-classified epilepsy. The subjects were compared with 1,722 control patients who showed definite subtypes of epilepsy. As a result, among the major causes of death, 13 of the subjects suffered accidents (mostly drowning), ten experienced sudden unexpected death, seven had status epilepticus, and six committed suicide. There were no significant differences with regard to clinical variables except for psychotic episodes, which were more frequently encountered in subjects than in controls (chi(2)=6.771, P=0.009, Yates' modification). Statistically significant differences were found by epilepsy type as well (chi(2)=14.72, P=0.002), with temporal lobe epilepsy (TLE) proving to be most closely associated with death among the epilepsy patients. Further, suicide was only encountered in patients with TLE and the association was statistically significant (chi(2)=5.119, P=0.024). Half of those who committed suicide (n=3), did so by jumping in front of an oncoming train while in the midst of an episode of postictal psychosis. In conclusion, most cases of suicide in patients with epilepsy were found to be the result of an immediate causal relationship with ictal or interictal epileptic manifestations, rather than a result of augmentation of psychosocial stressors generated by a long-standing handicap derived from the severe illness.     

A case of medial temporal lobe epilepsy associated with occult focal cortical dysplasia in the lateral temporal neocortex]

A 29-year-old male with medial temporal lobe epilepsy(MTLE) was revealed to have "occult" focal cortical dysplasia(FCD) in the lateral temporal neocortex. He had no history of febrile convulsion and developed complex partial seizure at the age of 14 year, which became intractable. Although MRI failed to reveal structural abnormality in the temporal lobe, even retrospectively, the findings of non-invasive preoperative examination, such as video-EEG monitoring and interictal ECD-SPECT and FDG-PET, were consistent with those of the left MTLE. Intraoperative electrocorticography(ECoG) demonstrated almost continuous paroxysmal activities on the anterior part of the inferior temporal gyrus(ITG). Anterior temporal lobectomy(ATL) with hippocampectomy was performed. Histological examination revealed FCD in the small area with 0.8 mm in diameter of the resected ITG. In the ATL without preoperative invasive examination such as chronic subdural electrode recording, intraoperative ECoG recording is mandatory.     

Two phase imaging of<Superscript>99m</Superscript>Tc-SESTAMIBI and<Superscript>123</Superscript>I-BMIPP for patients with angina pectoris

We saw three cases of angina pectoris in which 99mTc-SESTAMIBI delayed images at rest were useful in diagnosing ischemia risk areas. These findings indicated that delayed 99mTc-SESTAMIBI images may be more sensitive to slight ischemia than 123I-BMIPP images, and suggested that imaging with 99mTc-SESTAMIBI twice at rest may be more effective. The addition of 123I-BMIPP SPECT was considered to be useful in making an evaluation of the severity of ischemia.     

Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis.

Accumulating evidence indicates that overproduction of prostanoids attributable to overexpression of cyclooxygenase-2 (COX-2) plays an important role in colon carcinogenesis. We have shown recently that the prostaglandin (PG) E receptor, EP(1), but not EP(3), is involved in mouse colon carcinogenesis. In line with our previous study, here we examined the role of prostanoid receptors in colon carcinogenesis using six additional lines of knockout mice deficient in prostanoid receptors EP(2), EP(4), DP, FP, IP, or TP. The animals were treated with the colon carcinogen, azoxymethane (AOM), and examined for the development of aberrant crypt foci (ACFs), putative preneoplastic lesions in the colon. Formation of ACFs was decreased only in the EP(4)-knockout mice, to 56% of the wild-type level. To confirm these results, we also examined the inhibitory effects of an EP(4)-selective antagonist, ONO-AE2-227, in the diet on the formation of AOM-induced colon ACFs in C57BL/6Cr mice and on the development of intestinal polyps in Min mice. ONO-AE2-227 at a dose of 400 ppm reduced the formation of ACFs to 67% of the control level, and intestinal polyp numbers in Min mice receiving 300 ppm were decreased to 69% of the control level. Plating efficiency assays showed that addition of 1.0 microM ONO-AE1-329, an EP(4)-selective agonist, resulted in a 1.8-fold increase in the colony number of the human colon cancer cell line, HCA-7, similar to the effect of PGE(2). Moreover, EP(4) mRNA expression was clearly observed in normal colon mucosa and colon tumors in mice. Our previous and present results indicate that PGE(2) contributes to colon carcinogenesis through its actions mediated through EP(1) and EP(4) receptors; therefore, antagonists for these two receptors may be good candidates as chemopreventive agents against colon cancer.     

Role of thrombogenic factors in the development of atherosclerosis

Hemostatic factors play a crucial role in generating thrombotic plugs at sites of vascular damage (atherothrombosis). However, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis remains uncertain. Autopsy studies have revealed that intimal thickening represents the first stage of atherosclerosis and that lipid-rich plaque arises from such lesions. Several factors contribute to the start of intimal thickening. Platelets release several growth factors and bioactive agents that play a central role in development of not only thrombus but also of intimal thickening. We have been investigating which coagulation factors simultaneously, or subsequently with platelet aggregation, participate in thrombus formation. Tissue factor (TF) is an essential initiator of blood coagulation that is expressed in various stages of atherosclerotic lesions in humans and other animals. Factors including thrombin and fibrin, which are downstream of the coagulation cascade activated by TF, also contribute to atherosclerosis. TF is involved in cell migration, embryogenesis and angiogenesis. Thus TF, in addition to factors downstream of the coagulation cascade and the protease-activated receptor 2 activation system, would be a multifactorial regulator of atherogenesis.