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Biomedical subjects

M Makuuchi

Publications and source records attributed to M Makuuchi.

At least 199 records · Page 11Linked to original sources
PubMed1999

Prognostic significance of anatomical resection and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma.

BACKGROUND: Portal venous tumour extension and intrahepatic metastasis result in a poor prognosis following hepatectomy for hepatocellular carcinoma (HCC). Anatomical resection is, in theory, preferable for eradicating these types of invasion. Des-gamma-carboxy prothrombin (DCP) has been reported to be associated with adverse pathological variables. This study investigated the significance of anatomical resection and DCP as predictive factors for postoperative recurrence of HCC. METHODS: A retrospective cohort study was carried out in 138 consecutive patients who underwent hepatectomy for HCC smaller than 5 cm using the Cox proportional hazards model. RESULTS: Eight factors were univariately related to poor prognosis (in decreasing order of hazard ratio): intrahepatic metastasis, multiple tumours, alpha-fetoprotein 32 ng/ml or more; DCP greater than 0.1 arbitrary units (AU), tumour-exposed surgical margin, vascular invasion, non-anatomical resection and tumour 2.5 cm or more. Three variables (DCP, vascular invasion and tumour-exposed surgical margin) were excluded by a stepwise procedure in multivariate analysis. Although DCP was not an independent prognostic factor, a model replacing intrahepatic metastasis with DCP showed similar predictive accuracy in a receiver-operating characteristic curve. CONCLUSION: Anatomical resection appeared to have a beneficial effect on recurrence-free survival after hepatectomy for HCC. DCP measurement was effective in predicting HCC recurrence and had the advantage that it can be assessed before operation.

Biomarkers↗
PubMed1999

Region between alpha-helices 3 and 4 of the mad homology 2 domain of Smad4: functional roles in oligomer formation and transcriptional activation.

BACKGROUND: Smad4 has a unique region of 35 amino acids between alpha-helices 3 and 4 (termed H3/4 loop) of the Mad homology (MH) 2 domain. In order to elucidate the functional importance of the H3/4 loop, we prepared chimeric constructs of Smad4 containing the region corresponding to the alpha-helix 3, H3/4 loop and alpha-helix 4 of different Smads, including a chimera containing that of Smad2 (Smad4-HL2). RESULTS: Smad4-HL2 constitutively induced the transcriptional activation of p3TP-Lux, a TGF-beta-responsive reporter construct. However, co-transfection of Smad2 with Smad4-HL2 did not induce a further increase in the activation of p3TP-Lux. Smad4-HL2 did not induce the activation of pAR3-Lux, which contains FAST1-binding sites and is activated by a complex composed of FAST1, Smad2 and Smad4. Smad4-HL2 formed a homo-oligomer more efficiently than wild-type Smad4 in mammalian cells. Moreover, Smad4-HL2 bound to DNA containing the Smad-binding sites with a gretaer affinity than the wild-type Smad4. CONCLUSION: Smad4-HL2 spontaneously forms a homo-oligomer, which may bind to DNA with relatively high affinity and induce transcriptional activation of p3TP-Lux. The H3/4 loop of Smad4 may thus play a role in precluding the spontaneous oligomer formation of Smad4.

Animals↗
PubMed1999

Detection of hepatitis B virus DNA in tissues of hepatocellular carcinomas related to hepatitis C virus which are negative for hepatitis B virus surface antigen.

BACKGROUND: Uniform conclusions have not yet been drawn as to the frequency and copy number of hepatitis B virus (HBV) DNA in hepatocellular carcinoma (HCC) tissues from patients who are negative for hepatitis B surface antigen (HBsAg). METHODS: The existence of HBV DNA was investigated with Southern blot hybridization and polymerase chain reaction (PCR) in HCC tissues from 55 patients who were negative for HBsAg and positive for hepatitis C virus antibody (HCVAb). RESULTS: Southern blot hybridization showed that two tissues (4%) contained HBV DNA at a frequency of more than 1 HBV copy per 10 cells. Another 5 tissues were found to be positive for HBV DNA only by PCR analysis but contained less than 3 HBV DNA copies per 10(5) cells. CONCLUSIONS: HCC tissues from patients seronegative for HBsAg and seropositive for HCVAb contain HBV DNA less frequently than has generally been claimed.

Aged↗
PubMed1999

Metachronous bile duct cancer in a patient surviving for a decade and undergoing curative surgery twice.

We report a 75-year-old woman with metachronous bile duct cancer who underwent curative resection twice and has survived for a decade. In 1989, she was admitted because her serum alkaline phosphatase level was elevated. Computed tomography (CT) showed a low-density mass, 2 cm in diameter, at the left hepatic duct and intrahepatic bile duct dilatation in the left lobe. We diagnosed the lesion as an intrahepatic bile duct cancer and performed extended left hepatic lobectomy with systematic lymph node dissection. The histological diagnosis was a well differentiated cholangiocellular carcinoma with hepatic hilar and celiac lymph node metastases (T1N2M0, Stage IVB). In 1996, she was re-admitted with obstructive jaundice. CT showed a slightly enhanced mass, 4 cm in diameter, in the pancreatic head. After reducing the jaundice by percutaneous transhepatic biliary drainage, pancreatoduodenectomy was performed. The histological diagnosis of this lesion was a moderately differentiated adenocarcinoma originating from the intrapancreatic bile duct. Ten years after the first operation, she is leading a normal daily life with no cancer recurrence. These findings suggest that repeated curative surgery can result in a long-term survival of patients with metachronous bile duct cancer.

Adenocarcinoma↗
PubMed1999

Primary smooth muscle tumor of the liver encasing hepatobiliary cystadenoma without mesenchymal stroma.

We describe a 59-year-old Japanese woman with a large mass of her liver encasing cystic components. Radiologic imaging showed the mass to be hypervascular, and surgical resection disclosed a white tumor. The solid portion was immunohistochemically characterized as a smooth muscle tumor. The cystic components were multilocular and lined with columnar epithelium, consistent with a hepatobiliary cystadenoma. The epithelium strongly stained for CA19-9. The subepithelial space was occupied by collagenous connective tissue interspersed with a small number of spindle-shaped cells. The cystic lesions lacked the mesenchymal stroma between the epithelium and connective tissue layer. There have been no previous reports of a hepatic smooth muscle tumor encasing a hepatobiliary cystadenoma. Because of the pathogenesis of the cystadenoma, it is possible to assume that the smooth muscle tumor also arose from the cells composing the biliary duct in association with the development of the cystadenoma.

Biliary Tract Neoplasms↗
PubMed1999

Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection.

OBJECTIVE: To evaluate the long-term outcome of aggressive surgery incorporating hepatic resection and systematic nodal dissection for advanced carcinoma involving the hepatic hilus. SUMMARY BACKGROUND DATA: Few long-term results are available regarding radical surgery incorporating major hepatectomy and nodal dissection. METHODS: A retrospective analysis was undertaken in 107 patients with carcinoma involving the hepatic hilus treated between 1980 and 1997. Resectional surgery was performed in 65 patients, 52 of whom underwent major hepatectomies. The effects of clinical and pathologic factors were assessed by univariate and multivariate analyses. RESULTS: Sixty percent of the patients with resectional surgery had stage IVA or IVB disease, and 92.3% of them underwent major hepatectomies. No in-hospital deaths were encountered in the 35 most recent resections, whereas there were six deaths in the early period. Resectional surgery was associated with a survival benefit, especially when resection margins were free from cancerous infiltration. The estimated 5-year survival rate after resection, including all deaths, was 34.8%; this was 51.6% when the margins were clear. Nodal involvement was documented in 44.6% of the resections. However, patients with metastases limited to the regional nodes showed a survival rate similar to that in patients without nodal involvement. Significant predictive factors for survival after resection were extension to the gallbladder, nodal status, resectional margins, histologic type, and gender. CONCLUSIONS: The combination of major hepatectomy with systematic nodal dissection gave a good chance of prolonged survival for patients with carcinoma involving the hepatic hilus, even when the disease was advanced. Less-extensive procedures were also beneficial for less-advanced disease if clear resectional margins were secured.

Adult↗
PubMed1999

A rare combination consisting of primary hyperaldosteronism and glucagonoma.

A 59-yr-old man with multiple pancreatic tumors is presented. Previously, he had undergone left adrenalectomy for primary hyperaldosteronism and left nephrectomy for renal cell carcinoma at the ages of 39 and 55 yr, respectively. This time, 3 yr after removal of renal cancer, two solid lesions in the pancreas associated with hyperglucagonemia were detected. Under a diagnosis of pancreatic metastasis from renal cell carcinoma or islet cell tumor of the pancreas, distal pancreatectomy with splenectomy and enucleation of the tumor in the pancreas head were performed. Microscopically, a glucagonoma, measuring 2.3 mm in diameter, was detected among five pancreatic metastases from renal cell carcinoma. Four years after surgery, the patient remains well, without signs of recurrence despite multiple pancreatic metastases. This is the first report of such a rare combination consisting of aldosterone-secreting adrenal adenoma and glucagonoma.

Adrenal Cortex Neoplasms↗
PubMed1999

p53 and p21/Waf1 protein expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater.

OBJECTIVE: There have been few studies on the molecular biological characteristics of carcinoma of the papilla of Vater. In this study, p53 and p21/Waf1 expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater were investigated. METHODS: Thirty-seven cases of carcinoma of the papilla of Vater were studied. Macroscopically, the carcinoma was ulcerative in 15 cases and nonulcerative in 22 cases. Histologically, nine were intestinal type, 27 were pancreaticobiliary type, and one was undifferentiated. Formalin-fixed, paraffin-embedded sections were immunohistochemically stained for p53 and p21. K-ras codon 12 mutation was detected with the two-step polymerase chain reaction-restriction fragment length polymorphism method, followed by direct sequencing. RESULTS: p53 overexpression was found in 17 of 37 cases (46%) and was more frequent in the ulcerative type than in the nonulcerative type (67% vs 32%, p < 0.05). p21/Waf1 protein expression was found in 15 of 37 cases (41%), and was not correlated with that of p53. K-ras codon 12 mutation was found in 14 of 37 cases (38%), and was more frequently detected in the intestinal type than in the pancreaticobiliary type (66% vs 30%, p < 0.05). On direct sequencing, the mutations were mainly GGT to GAT (9/14) and GGT to GTT (4/14). The type of mutation did not correlate with the histological type. CONCLUSIONS: In carcinoma of the papilla of Vater, p53 overexpression may play a role in tumor ulceration. p21/Waf1 expression is induced via a p53-independent pathway. Carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms, and K-ras mutation is mainly associated with the intestinal type.

Adult↗
PubMed1999

Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important growth factors in the generation of new blood vessels. We investigated Ang expression in 23 samples of HCC and paired adjacent uninvolved liver samples to determine if these genes have a potential role in the growth and spread of this disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and hemorrhage were determined in an animal model system. Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC cells promotes the rapid development of human hepatomas and produces hemorrhage within tumors in nude mice. These results suggest a role for Ang2 in the neovascularization of HCC. This enhanced gene expression may contribute to the clinical hypervascular phenotype, as well as tumor formation and progression.

Amino Acid Sequence↗
PubMed1999

[Improving the anti-tumor activity of 5-fluorouracil by methotrexate].

The first clinical application of biochemical modulation (BCM) of 5-fluorouracil (5-FU) was the sequential MTX/5-FU regimen proposed in 1977 by Bertino for the treatment of colorectal cancer. In Japan, sequential MTX/5-FU therapy was mainly used as a new method of treating gastric cancer, and attracted a great deal of attention because it proved effective in many cases of advanced gastric cancer that had been unresponsive to the previous chemotherapy, particularly scirrhous gastric cancer with poor prognosis. Its therapeutic efficacy varied according to histologic type, it was effective in cases of peritoneal dissemination and disseminated intravascular coagulopathy (DIC), it was associated with fewer adverse effects, and it was a multidrug chemotherapy based on a clear rationale. With sequential MTX/5-FU therapy as a starting point, fundamental studies of BCM and its clinical applications have expanded rapidly in Japan. This paper provides an outline of sequential MTX/5-FU therapy from the aspects of its mechanism of action, indications, therapeutic efficacy, relevance to adjuvant therapy, counter-measures to adverse effects, and emergence of resistance to the drugs involved. The high therapeutic efficacy of this therapy in certain histologic types is also discussed, and its combined use with other forms of BCM, as in triple BCM (LV/5-FU + CDDP/5-FU + MTX/5-FU), is introduced.

Animals↗
PubMed1999

Proximal bile duct stricture disguised as malignant neoplasm.

BACKGROUND: Discrimination of malignant proximal bile duct (PBD) stricture from a benign lesion is difficult with nonsurgical methods; indeed, 8% to 13% of PBD strictures prove to be benign after histologic examination of the surgically resected specimen. METHODS: In a 7-year period 178 patients with PBD stricture were admitted, and 99 of them underwent radical resection for presumably malignant lesions. In 14 of these patients the stenotic lesions were proved to be benign by postoperative histologic assessment. We reviewed these patients retrospectively by collecting data from their charts. RESULTS: Preoperative radiologic findings including cholangiography and angiography were compatible with malignancy in all 14 patients. Preoperative histologic studies suggested malignancy in 2 of 8 examined. Findings at laparotomy could not allow differentiation between malignant and benign lesions in any of the patients and strongly suggested malignancy in 3. Histologic examination of the resected specimens revealed extensive fibrosis with inflammatory cellular infiltration in all patients. There was 1 episode of significant morbidity postoperatively (transient cholangitis) but no mortality. CONCLUSION: Benign PBD strictures, although rare, are usually indistinguishable from malignant PBD strictures by preoperative or perioperative investigation. Given the minimal morbidity, all PBD strictures should be presumed malignant and managed accordingly, even at the risk of overtreating some benign cases.

Aged↗
PubMed1999

[Selective and unselective clamping in liver surgery].

Liver surgery requires a reduction in the operative blood loss to avoid postoperative liver failure. We carried out elective hepatic resection in 229 patients with Pringle's maneuver, which involves complete, intermittent clamping of the hepatic flow, and in 56 patients with selective vascular occlusion. Twenty-seven donors for living-related liver transplantation were also included in the latter series. The clinical outcomes were evaluated based on clamping method used. The cumulative clamping time and amount of blood loss were 64 +/- 46 min (mean +/- SD) and 828 +/- 665 ml in the Pringle's maneuver group and 88 +/- 44 min and 907 +/- 555 ml in the selective vascular occlusion group. Laboratory data showed good tolerance of vascular clamping in both groups, and serum aspartate aminotransferase levels returned to the baseline within one week. Operative morbidity rates were 23% and 27%, respectively, and no operative deaths occurred in this series. In living-related liver transplantation, modified selective vascular occlusion can preserve graft viability, as verified by the fact that all the recipients in this series had a good postoperative course, except for one death and one graft loss. In conclusion, intermittent total or selective vascular clamping is indispensable procedure during hepatic resection.

Constriction↗
PubMed1999

A comparative study of postoperative complications after hepatectomy in patients with and without chronic liver disease.

BACKGROUND: Although hepatic resection is the most reliable treatment for hepatocellular carcinoma, impaired liver function because of cirrhosis or chronic hepatitis contributes to relatively high rates of postoperative complications. We have reviewed a series of hepatectomies at our institution and investigated risk factors for complications after hepatectomy in patients with impaired liver compared with patients with normal liver. METHODS: From October 1994 to March 1998, 277 hepatectomies for hepatocellular carcinoma, cholangiocellular carcinoma, metastatic liver tumors, and other hepatic diseases were performed. In an attempt to clarify the safety of hepatectomy for the impaired liver at our institution, we did a comparative study of postoperative complications after hepatectomy in 2 groups: patients with impaired livers (187 hepatectomies) and patients with normal livers (90 hepatectomies). RESULTS: Of the 277 hepatectomies, bile leakage occurred in 25 patients (16 in impaired livers vs 9 in normal livers), abdominal infection in 45 patients (30 vs 15 patients), wound infection in 13 patients (9 vs 4 patients), pleural effusion in 52 patients (35 vs 17 patients), atelectasis in 26 patients (17 vs 9 patients), pneumonia in 4 patients (3 vs 1 patients), ileus in 6 patients (3 vs 3 patients), intra-abdominal hemorrhage in 3 patients (0 vs 3 patients), and hyperbilirubinemia in 5 patients (4 vs 1 patients). Hepatic insufficiency and hospital death were not experienced in this series. The mean postoperative hospital stay was 22.9 days (23.5 vs 23.1 days), and except for intra-abdominal hemorrhage there was no statistically significant difference between the 2 groups. CONCLUSIONS: Hepatectomy for the impaired liver is now as safe a procedure as for the normal liver, provided the overall guidelines outlined in our algorithm are followed.

Adolescent↗
PubMed1999

Increased expression of ornithine decarboxylase messenger RNA in human esophageal carcinoma.

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines, which are essential for cell proliferation. The purpose of this study was to evaluate ODC expression in human esophageal cancer at the mRNA level. Sixty-four pairs of primary esophageal cancers and normal esophageal epithelia were examined by reverse transcription-PCR for ODC mRNA expression. The ODC mRNA levels were higher in primary esophageal carcinoma than in adjacent normal esophageal epithelium in 58 (90.6%) of 64 cases. The tumor:normal (T:N) ratio of ODC mRNA expression in esophageal specimens has a significant correlation with tumor-node-metastasis staging (P = 0.043), lymph node metastasis (P = 0.039), vascular vessel invasion (P = 0.035), and histology (P = 0.034) of the tumor. In well- and moderately differentiated squamous cell carcinoma, the patients with a higher T:N ratio showed a significantly poorer prognosis (P = 0.027), and multivariate analysis also confirmed that the T:N ratio has a significant correlation with poor prognosis (P = 0.043). The steady-state of ODC mRNA overexpression in esophageal carcinoma implies that the ODC gene may play an important role in tumorgenesis in squamous epithelium. Furthermore, ODC mRNA expression may be used as a prognostic marker, especially for well- and moderately differentiated squamous cell carcinoma.

Age Factors↗
PubMed1998

Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.

Insulin resistance is often associated with atherosclerotic diseases in subjects with obesity and impaired glucose tolerance. This study examined the effects of insulin resistance on coronary risk factors in IRS-1 deficient mice, a nonobese animal model of insulin resistance. Blood pressure and plasma triglyceride levels were significantly higher in IRS-1 deficient mice than in normal mice. Impaired endothelium-dependent vascular relaxation was also observed in IRS-1 deficient mice. Furthermore, lipoprotein lipase activity was lower than in normal mice, suggesting impaired lipolysis to be involved in the increase in plasma triglyceride levels under insulin-resistant conditions. Thus, insulin resistance plays an important role in the clustering of coronary risk factors which may accelerate the progression of atherosclerosis in subjects with insulin resistance.

Animals↗
PubMed1998

Risk factors for hyperamylasemia after hepatectomy using the Pringle maneuver: randomized analysis of surgical parameters.

OBJECTIVES: To determine whether the increased portal venous pressure caused by use of the Pringle maneuver contributes to inducing posthepatectomy hyperamylasemia and, subsequently, to evaluate risk factors for its development. DESIGN: Randomized study. SETTING: University hospital. PATIENTS: Forty patients who were going to undergo hepatectomy were assigned prospectively to either a superior mesenteric artery clamp (n=20) or a nonclamp (n=20) group by the random-block method. INTERVENTIONS: The Pringle maneuver was used during hepatectomy, and in the superior mesenteric artery clamp group the superior mesenteric arteries were clamped simultaneously. MAIN OUTCOME MEASURES: Amylase activity, isozyme, and creatinine levels in the blood and urine samples were measured before and after surgery, and the amylase creatinine clearance ratio was estimated. RESULTS: The serum amylase activity levels of the superior mesenteric artery clamp and nonclamp groups did not differ significantly during the 7 postoperative days. The serum amylase activity levels exceeded 250 U/L in 14 patients (group 1) and remained below this level in 26 (group 2). The salivary-type isozyme levels of group 1 increased significantly compared with those of group 2, and the levels of group 2 remained normal. The total amount of amylase excreted in the urine samples of group 1 patients also increased significantly, with the salivary-type isozyme predominating. All the mean amylase creatinine clearance ratios before and after surgery remained normal. The mode chi2 of the logistic model including the indocyanine green retention rate at 15 minutes and the ratio of the resected liver weight to the whole liver volume showed a significantly increased risk (P=.01). CONCLUSION: It is not the increased portal venous pressure caused by use of the Pringle maneuver but the liver function and the extent of liver resection that are considered risk factors for inducing posthepatectomy salivary-type hyperamylasemia.

Aged↗