Deceleration of regenerative response improves the outcome of rat with massive hepatectomy.

Small residual liver volume after massive hepatectomy or partial liver transplantation is a major cause of subsequent liver dysfunction. We hypothesize that the abrupt regenerative response of small remnant liver is responsible for subsequent deleterious outcome. To slow down the regenerative speed, NS-398 (ERK1/2 inhibitor) or PD98059 (selective MEK inhibitor) was administered after 70% or 90% partial hepatectomy (PH). The effects of regenerative speed on liver morphology, portal pressure and survival were assessed. In the 70% PH model, NS-398 treatment suppressed the abrupt replicative response of hepatocytes during the early phase of regeneration, although liver volume on day 7 was not significantly different from that of the control group. Immunohistochemical analysis for CD31 (for sinusoids) and AGp110 (for bile canaliculi) revealed that lobular architectural disturbance was alleviated by NS-398 treatment. In the 90% PH model, administration of NS-398 or PD98059, but not hepatocyte growth factor, significantly enhanced survival. The abrupt regenerative response of small remnant liver is suggested to be responsible for intensive lobular derangement and subsequent liver dysfunction. The suppression of MEK/ERK signaling pathway during the early phase after hepatectomy makes the regenerative response linear, and improves the prognosis for animals bearing a small remnant liver.

'Scirrhous' type hepatocellular carcinomas: a special reference to expression of cytokeratin 7 and hepatocyte paraffin 1.

AIMS: 'Scirrhous' hepatocellular carcinoma (scirrhous HCC) is extremely rare and its characteristics remain unclear. We investigated the clinicopathological and immunohistochemical features of scirrhous HCC, compared with those of ordinary hepatocellular carcinoma (ordinary HCC). METHODS AND RESULTS: We compared the clinicopathological and immunohistochemical features of 20 resected cases of scirrhous HCC with those of 69 resected cases of ordinary HCC. Scirrhous HCC was characterized by its gross and histological findings, such as a higher proportion of contiguous multinodular type tumours, the absence of a complete fibrous capsule around the tumour, the absence of tumour necrosis and highly preserved portal tracts in the tumour. The immunohistochemical results revealed a significantly higher expression of cytokeratin 7 and a significantly lower expression of hepatocyte paraffin 1 in scirrhous HCC than in ordinary HCC (P<0.0001, respectively). There were no significant differences in proliferative activity and survival curves between the patients with scirrhous HCC and those with ordinary HCC. CONCLUSION: Scirrhous HCC has several particular gross, histological and immunohistochemical features. In particular, we would like to emphasize the greater immunohistochemical expression of cytokeratin 7 and lower expression of hepatocyte paraffin 1 in scirrhous HCC than in ordinary HCC.

Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. METHODS: Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. RESULTS: The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. CONCLUSIONS: A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.

[Collateral blood flow showing dissection-like filling defect on coronary arteriography: a case report].

A 51-year-old man presented under a diagnosis of angina pectoris manifesting as exertional chest pain. First coronary angiography showed severe stenosis with ulceration and spontaneous dissection at the proximal right coronary artery and linear dissection-like filling defects extending to the distal right coronary artery. After about 3 months, repeat coronary angiography showed the previously observed stenosis with unclear dissection, and better developed collaterals from the left coronary artery to the right coronary artery showing the linear dissection-like filling defects. The bilateral coronary angiography did not clearly show filling defects. This phenomenon suggested that the collateral flows were related to filling of the defects. Intravascular ultrasonic imaging demonstrated severe atherosclerotic lesions at the proximal right coronary artery, but no dissection in the distal right coronary artery. Percutaneous transluminal coronary angioplasty for the stenosis was performed successfully with a stent. Coronary angiography after the angioplasty showed no collaterals, and the right ventricular branch appeared, suggesting that the linear dissection-like filling defects extending to the distal right coronary artery were due to the collateral flows. Filling defects extending distal to a severe stenosis must be distinguished carefully from coronary dissection.

The role of macroscopic classification in nodular-type hepatocellular carcinoma.

BACKGROUND: Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. METHODS: Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. RESULTS: The alpha-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. CONCLUSIONS: Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.

[Aneurysm-like wall motion abnormality in hibernating myocardium detected by stress thallium scintigraphy].

A 70-year-old female patient presented and ECG with QS patterns and ST elevation in V1-3. Left ventriculography showed severely abnormal wall motion of the anteroseptal similar to a left ventricular aneurysm. Based on previous experience that 201Tl myocardial scintigraphy revealed possible myocardial viability in a patient with left ventricular aneurysm suspected of having apparently no myocardial viability, percutaneous transluminal coronary angioplasty (PTCA) was performed for severe stenosis of the left anterior descending artery. Follow-up images 3 months later showed a remarkable improvement in parietal motility of the left ventricle and recovery of almost normal cardiac function. This case demonstrates that exercise myocardial scintigraphy is useful for diagnosing hibernating myocardium associated with severely abnormal parietal motility, such as left ventricular aneurysm.

[Living donor liver transplantation in Kyushu University].

We performed living donor liver transplantation (LDLT) for 40 patients at Kyushu University Hospital, Fukuoka Japan during the period from October 1996 to April 2000. The patients consisted of 32 adults and 8 children with a mean age of 35.8 years (range: 1 year and 10 months to 65 years old). The underlying liver diseases of the 40 patients included the fulminant hepatic failure (n = 14), biliary atresia (n = 7), liver cirrhosis (HCV) (n = 6), primary biliary cirrhosis (n = 5), primary sclerosing cholangitis (n = 2), familiar amyloidotic polyneuropathy (n = 2), Alagille syndrome (n = 1), glycogen storage disease (n = 1), huge hepatic hemangiomas (n = 1), and Wilson's disease (n = 1). All liver grafts were obtained from each patient's family members except for one domino transplant donor's case, comprised of 13 parents, 13 sons and daughters, 11 brothers and sisters, and 3 wives. The donors are presently all doing well. The patient survival rate is presently 92.5%.

Malformation of trachea and pelvic region in goosecoid mutant mice.

The homeobox gene goosecoid is expressed in the Spemann organizer tissue of gastrulating vertebrate embryos, and in the craniofacial region and appendicular skeleton during organogenesis. The goosecoid knockout mutant mouse revealed defects related to the second phase of expression. Here we describe new expression sites in the developing trachea and external genitalia, and in the developing shoulder and hip joint with their associated ligaments and muscles. We show that mutant mice display abnormalities in the forming trachea and appendicular skeleton related to these sites of gene expression. In addition, we discuss evidence for the existence of at least three goosecoid genes in vertebrates, which may account for the lack of a defect of axial patterning in goosecoid mutant mice.

An efficient liposome-mediated gene transfer into the branchial arch, neural tube and the heart of chick embryos; a strategy to elucidate the organogenesis.

Hemagglutinating virus of Japan (HVJ)-liposome mediated gene-transfer permitted to clarify the mechanisms of embryonic organogenesis of the branchial arches, neural tubes and heart by micro-injecting reporter-plasmid DNA, containing the Escherichia coli LacZ gene, in embryos at several stages.