Search PubMed⌕ Search

Biomedical subjects

M Makuuchi

Publications and source records attributed to M Makuuchi.

At least 145 records · Page 8Linked to original sources

p27(Kip1) expression in normal epithelia, precancerous lesions, and carcinomas of the gallbladder: association with cancer progression and prognosis.

p27(Kip1) is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation. This study was designed to evaluate the roles of p27(Kip1) in gallbladder carcinogenesis and the prognostic value of p27(Kip1) in patients with gallbladder carcinoma. p27(Kip1) expression was examined immunohistochemically in surgically resected specimens of 8 normal epithelia, 8 adenomyomatosis lesions, 6 precancerous adenomas, and 37 carcinomas of the gallbladder. Decreased p27(Kip1) expression (<50% nuclear staining) was observed in 16 of the 37 (43%) gallbladder carcinomas, but not in any specimen of normal epithelium, adenomyomatosis, or adenoma. The fact that all of the adenomas showed normal p27(Kip1) expression suggests that decreased p27(Kip1) expression is probably not an early event in gallbladder carcinogenesis. Decreased p27(Kip1) expression was significantly associated with less marked tumor cell differentiation (P =.017), lymphatic invasion (P =.046), lymph node metastasis (P =.007), and advanced TNM stage (stage IV vs. stage I, P =.026; stage IV vs. stage II, P =.005). This suggests that down-regulation of p27(Kip1) expression is a late event in gallbladder carcinogenesis, possibly promoting tumor progression and metastasis. Kaplan-Meier curves showed that decreased p27(Kip1) expression was significantly associated with shorter overall survival (P =.001) in patients with gallbladder carcinomas who had undergone radical surgery. Cox's proportional hazards model revealed decreased p27(Kip1) expression to be an independent predictor for death (P =.034; risk ratio, 3.9; 95% confidence interval, 1.1-13.7). In conclusion, decreased p27(Kip1) expression significantly correlates with tumor progression and predicts poor prognosis in gallbladder carcinomas.

Adenoma↗

Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan.

Hepatic resection (HX), percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TCAE) have all been used in the treatment of patients with small-sized hepatocellular carcinomas (HCCs). However, the indications for these therapeutic modalities remain unclear. Therefore, the first step to minimize the debate on these indications is to review the standard results from each treatment based on an extensive survey. The participants in this study were patients with HCCs less than 5 cm in diameter who were enrolled in The Liver Cancer Study Group of Japan. The survival rates in the HX (n = 8,010), PEI (n = 4,037), and TCAE (n = 841) groups were calculated in relation to the number of tumors and the clinical stage. In the clinical stage I cases with a solitary tumor less than 2 cm in diameter and in all clinical stages with a solitary tumor greater than 2 cm and in the clinical stage II cases with 2 tumors greater than 2 cm, the HX group showed higher survival rates than the nonsurgical groups. The HX group had a higher male/female ratio and a younger mean age than the PEI or TCAE group. The ratio of HBs antigen-positive cases/hepatitis C virus antibody-positive cases in the PEI group was lower than that in the corresponding HX group. In contrast, the PIVKA-II values in the HX group tended to be higher than in the PEI group. In conclusion, these findings will provide useful information for selection of a therapeutic modality for small-sized HCCs.

Age Distribution↗

Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53 in hepatocellular carcinomas.

To investigate the relationship between the expression of p21(WAF1/CIP1) protein and p53 status and the possible role of the two proteins in hepatocellular carcinomas (HCCs), we examined the expression of p21(WAF1/CIP1) and p53 immunohistochemically in 81 tumours from 65 patients with hepatocellular carcinoma. p21(WAF1/CIP1) protein was absent from 59 of 81 tumours (72.8%), and altered p53 expression was found in 43 (53.1%). p21(WAF1/CIP1) expression was significantly associated with p53 status (P = 0.0008); 38 of 59 tumours lacking p21(WAF1/CIP1) protein were accompanied by altered p53 expression. Further analyses showed that p21(WAF1/CIP1) expression was inversely correlated with p53 expression in hepatitis C virus (HCV)-related HCCs, but not in HBV-related hepatocellular carcinomas and hepatocellular carcinomas without viral infection. All 11 tumours with intrahepatic metastasis showed altered p21(WAF1/CIP1) or p53 expression. In contrast, no intrahepatic metastasis was found in any of the 17 tumours without abnormal expression of either of the two proteins. These results suggest that: (1) different modes of p21(WAF1/CIP1) regulation are involved in HCCs differing in their hepatitis viral infection status, and p21(WAF1/CIP1) expression appears to be predominantly related to altered p53 in HCV-related HCCs; (2) disruption of the p53-p21(WAF1/CIP1) cell-cycle-regulating pathway may contribute to malignant progression of HCC.

Adolescent↗

Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma.

BACKGROUND: Mass-forming type cholangiocarcinoma is a distinct from of cholangiocellular carcinoma, with pathologic and biologic behavior different from those of other types. The clinical consequences of these differences have never been clarified. METHODS: Fifty-two consecutive patients (32 men and 20 women, mean age 62 years) with mass-forming type cholangiocarcinoma that had been treated with curative surgical resection between 1980 and 1998 were retrospectively evaluated. Long-term survival and disease-free survival were calculated, and univariate and multivariate analysis of various prognostic factors was conducted. RESULTS: The 30-day postoperative mortality rate was 2%, and the overall and disease-free 5-year survival rates were 36% and 34%, respectively. Univariate analysis identified 5 significant risk factors for overall survival: surgical margin, lymph node metastasis, lymph node dissection, vascular invasion, and left-side location of the main tumor. Two risk factors were identified for disease-free survival: surgical margin and lymph node metastasis. Multivariate analysis confirmed that surgical margin, lymph node metastasis, and vascular invasion were independently significant variables for overall survival. CONCLUSIONS: This is the first reported study on the effectiveness of liver resection for the treatment of mass-forming type cholangiocarcinoma, showing that surgical therapy can prolong survival if local radicality can be achieved and lymph-node metastases are absent.

Adult↗

Successful hepatic vein reconstruction in 42 consecutive living related liver transplantations.

BACKGROUND: In living related liver transplantation (LRLT), reconstruction of the hepatic vein (HV) by end-to-end anastomosis has been reported to be associated with acute or late outflow block. METHODS: We reviewed 42 patients who underwent LRLT from January 1996 to September 1998. RESULTS: In 7 (27%) of the 26 donor grafts obtained from left lateral segmentectomy or extended lateral segmentectomy and in 9 (56%) of the 16 grafts obtained from left lobectomy, venoplasty was required. In the remaining 26 grafts, 1-orifice left HV was obtained. In addition to the division of the duct of Arantius, the left inferior phrenic vein was divided routinely in 16 patients, which contributed to reducing the venoplasty rate from 46% to 25% (P =.1704). In all 42 patients, HV was reconstructed successfully by end-to-end anastomosis. The median ratio of the diameter of the recipient's HV to that of the graft's HV was 1.2 (range, 0.8-2.1). The grafts were fixed to the abdominal wall by using the falciform and round ligaments at a site where Doppler ultrasound showed sufficient flow in the respective vessels. Three patients developed late-onset HV obstruction and required balloon dilatation either by means of a venous route or a transhepatic route: 1 patient received a new liver on the 232nd postoperative day, 1 patient died of sepsis without outflow block, and the last patient is doing well. CONCLUSIONS: In LRLT, the division of the duct of Arantius and the left inferior phrenic vein followed by extensive clamping of the common trunk contributed to obtaining a 1-orifice HV. This facilitates anastomosis of the HVs of the grafts to the recipients' HVs, and fixation of the grafts by using the falciform and round ligaments prevents rotation of the grafts and subsequent acute outflow block.

Adult↗

Anatomical segmentectomy of the head of the pancreas along the embryological fusion plane: a feasible procedure?

BACKGROUND: Less extensive resection of the head of the pancreas has been the procedure of choice recently for low-grade malignant neoplasms. The anatomical detail of the head of the pancreas is currently insufficient for segmental resection along the embryological fusion plane. METHODS: The anatomy of the head of the pancreas was analyzed in 31 consecutive autopsy specimens. An anterior (n = 10) or posterior (n = 10) segmentectomy of the head of each pancreas was performed along the macroscopically found fusion plane. The pancreatic arteries, the portal vein, the bile duct, and the pancreatic duct were visualized by injecting 3 silicon dyes of different colors. Another 11 specimens were examined by pancreatography before and after anterior (n = 5) or posterior (n = 6) segmentectomy. Eight of these 11 specimens were stained immunohistochemically to reveal the distribution of pancreatic polypeptide cells after segmentectomy. RESULTS: The cleavage between the anterior and posterior segments was discovered at the anterior inferior edge or at the posterior superior edge of the head of the pancreas. Anterior segmentectomy was accomplished while preserving the anterior and posterior pancreaticoduodenal arcades and the lower bile duct in the posterior segment. Posterior segmentectomy involved the removal of the lower bile duct and the posterior pancreaticoduodenal arcades. Pancreatography after segmentectomy showed the division of the ducts of Wirsung and Santorini with the peripheral branches. The immunohistochemical boundary of pancreatic polypeptide cells coincided with the surgical plane. These results showed the anterior and posterior segments were originated from the embryologically dorsal and ventral primordia, respectively. CONCLUSIONS: The current anterior or posterior segmentectomy of the head of the pancreas corresponded to the resection of the embryologically dorsal or ventral primordium, respectively. Anterior segmentectomy of the head of the pancreas might be a clinically applicable procedure; however, posterior segmentectomy involving the resection of the lower bile duct may be impractical.

Adult↗

In vivo retention of endothelial cells adenovirally transduced with tissue-type plasminogen activator and seeded onto expanded polytetrafluoroethylene.

PURPOSE: Seeding a prosthetic graft with genetically engineered vascular endothelial cells (ECs) has the potential to enhance the graft's antithrombotic properties. However, it has been reported that ECs transduced with tissue-type plasminogen activator (tPA) have very low levels of retention on grafts, probably because of increased proteolytic activity. We examined the retention of human tPA (htPA)-transduced ECs after the cells were seeded onto expanded polytetrafluoroethylene (ePTFE) grafts and implanted into dogs. We also examined the function of secreted htPA in this model. METHODS AND RESULTS: Canine jugular venous ECs were transduced with adenoviral vectors encoding htPA (Adex1CAhtPA) and beta-galactosidase (Adex1CALacZ). There was a positive relationship between the percentage of X-gal ECs staining and the multiplicity of infection (MOI) of Adex1CALacZ. The level of htPA production in vitro increased with the increasing MOI of Adex1CAhtPA, but decreased gradually 4 days after infection. ECs coinfected with Adex1CAhtPA and Adex1CALacZ (htPAEC) or ECs infected with Adex1CALacZ alone (LacZEC) were seeded onto ePTFE grafts at densities equivalent to confluence to visualize retained ECs in an in vivo flow study. The grafts were implanted into canine carotid arteries and harvested after 5 hours of exposure to blood flow. The harvested grafts showed patchy defects in ECs, most of which were covered with mural thrombi. There was no significant difference in retention between htPAEC (29.3% +/- 8.7%) and LacZEC (19.5% +/- 3. 6%). There was a significant negative correlation between the in vivo EC retention on the grafts and the in vitro cellular passage level of ECs (P =.041; r = -.40). htPAEC produced 210.3 +/- 22.2 ng htPA antigen/10(6) cells per 6 hours in vitro and continued to secrete htPA on the harvested graft. CONCLUSIONS: We demonstrated that a large amount of functional htPA was produced by adenovirally modified canine ECs. The results of the in vivo study may suggest that overexpression of tPA has little effect on the short-term retention of early passage ECs seeded onto ePTFE grafts.

Adenoviridae↗

Detection of Epstein-Barr virus DNA in hepatocellular carcinoma tissues from hepatitis C-positive patients.

BACKGROUND: We have previously shown that hepatitis C virus (HCV) replication is promoted by the Epstein-Barr virus (EBV) in vitro. The aim of this study was to examine the EBV load in hepatocellular carcinoma (HCC) tissues from HCV antibody-positive patients. METHODS: DNA was extracted from paraffin sections from 168 HCC patients. After amplification of a region in the EBV BamHI W sequence by means of the polymerase chain reaction (PCR), it was detected by Southern hybridization and semi-quantified. Ten hyperplastic lesions from HCV-positive patients and 35 non-tumorous samples from hepatitis-negative patients served as controls. The PCR results were analyzed on the basis of the patient's hepatitis status. Univariate and multivariate analyses were performed to identify clinicopathologic factors for predicting EBV infection in HCC tissues. RESULTS: More than one copy of EBV DNA per 100 cells was detected in 56 (33%) of the HCC sections. The detection ratio in HCC tissues from HCV antibody-positive patients was 40% (45 of 113), which was significantly higher than that in tissues from HBV surface antigen-positive patients (14%, 5 of 37; P = 0.0018). The patient's serum HBV surface antigen and HCV antibody independently predicted the EBV positivity of HCC tissues. CONCLUSIONS: These results support our hypothesis that EBV could play an important role in the development of HCV-related HCC.

Blotting, Southern↗

Effects of amrinone on ischaemia-reperfusion injury in cirrhotic patients undergoing hepatectomy: a comparative study with prostaglandin E1.

The effects of amrinone, a selective phosphodiesterase III inhibitor, on liver ischaemia reperfusion injury have not yet been clarified. Forty-five patients with hepatocellular carcinoma who underwent partial liver resection using Pringle's manoeuvre were studied. Patients were divided into three groups: those given amrinone, those given prostaglandin E1 (PGE1) and those not treated (controls). An indocyanine green (ICG) clearance test was performed before the operation and three times during surgery: just before induction of liver ischaemia, just after liver resection and 60 min after reperfusion. Blood lactate and base excess were measured at the same times. Systolic and diastolic arterial pressure, heart rate, cardiac index and oesophageal temperature were monitored. Aminotransferase levels were recorded the day before surgery, 1 h after operation and on the first and third postoperative days. These data were compared between groups. The ICG elimination rate, lactate and base excess in the amrinone group differed significantly from those in controls during the observation period (P = 0.03, P = 0.04 and P = 0.03, respectively). The differences between the PGE1 and control groups were not significant. There were no significant differences between the groups in perioperative vital signs, cardiac index or postoperative aminotransferase. Amrinone enhanced intraoperative ICG elimination in cirrhotic patients who underwent liver resection.

Aged↗

Adrenalectomy for solitary adrenal metastasis from colorectal carcinoma.

A 60-year-old man underwent anterior resection for advanced rectal carcinoma. Seven years and 2 months later, right lower pneumonectomy was performed for a metastatic lung tumor. Two years and 2 months thereafter, left adrenalectomy was performed for solitary adrenal metastasis. The patient remained disease-free for 10 months postoperatively, until multiple lung metastases appeared. The patient is alive and well, under mild chemotherapy with oral doxifluridine, 3 years and 5 months after left adrenalectomy. We conclude that patients with solitary adrenal metastasis may benefit from surgical resection and that resection could be considered as a therapy for solitary adrenal metastasis from colorectal carcinoma.

Adrenal Gland Neoplasms↗

Relation among portal segmentation, proper hepatic vein, and external notch of the caudate lobe in the human liver.

OBJECTIVE: To identify portal segmentation and a portal fissure in the caudate lobe of the human liver in relation to the hepatic venous system and the external notch at the caudal edge of the caudate lobe. SUMMARY BACKGROUND DATA: Although the anatomy of the caudate lobe has been studied, the detailed anatomy has not yet been clarified; this is necessary to develop safe procedures for caudate lobe resection. METHODS: A total of 88 formalin-fixed human livers were dissected to visualize the portal vein and hepatic vein systems of the caudate lobe in relation to the external notch. RESULTS: The patterns of portal branching were classified into two types. In 58 livers (67.4%), the territories of the first-order portal branches were clearly divided into two areas (the Spiegel lobe and the paracaval portion). In the remaining 28 livers (32.6%), the territories of the second-order portal branches were clearly divided into two areas. These two areas were distinctly separated by an internal plane, which was coincident with the external notch. The caudate lobe had a systematized hepatic venous system that consisted of one (87.5%) or two (11.4%) proper hepatic veins and plural accessory hepatic veins. The proper hepatic veins laid along the internal plane between these two portal areas. CONCLUSION: The caudate lobe exhibited distinct portal segmentation with a portal fissure that was indicated internally by the proper hepatic vein and externally by the notch at the caudal edge of the caudate lobe.

Adult↗

Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results.

OBJECTIVE: To evaluate retrospectively the long-term results of an approach consisting of performing surgery in every patient in whom radical removal of all metastatic disease was technically feasible. SUMMARY BACKGROUND DATA: The indications for surgical resection for liver metastases from colorectal cancer remain controversial. Several clinical risk factors have been reported to influence survival. METHODS: Between March 1980 and December 1997, 235 patients underwent hepatic resection for metastatic colorectal cancer. Survival rates and disease-free survival as a function of clinical and pathologic determinants were examined retrospectively with univariate and multivariate analyses. RESULTS: The overall 3-, 5-, 10-, and 15-year survival rates were 51%, 38%, 26%, and 24%, respectively. The stage of the primary tumor, lymph node metastasis, and multiple nodules were significantly associated with a poor prognosis in both univariate and multivariate analyses. Disease-free survival was significantly influenced by lymph node metastasis, a short interval between treatment of the primary and metastatic tumors, and a high preoperative level of carcinoembryonic antigen. The 10-year survival rate of patients with four or more nodules (29%) was better than that of patients with two or three nodules (16%), and similar to that of patients with a solitary lesion (32%). CONCLUSIONS: Surgical resection is useful for treating liver metastases from colorectal cancer. Although multiple metastases significantly impaired the prognosis, the life expectancy of patients with four or more nodules mandates removal.

Adenocarcinoma↗

Significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor in carcinoma of the papilla of Vater.

The expression of thymidine phosphorylase (TP) in carcinoma of the papilla of Vater was studied to clarify its significance in tumor progression and in determining prognosis. Fifty-nine cases of surgically resected carcinoma of the papilla of Vater were studied. Immunohistochemical staining was performed to evaluate the expression of TP, microvessel count and p53 overexpression. TP expression was demonstrated in tumor cells in 62.7% (37/59) of the cases. A higher frequency of regional lymph node metastasis was found in TP-positive tumors than in TP-negative tumors (P = 0.006). TP-positive tumors were more advanced than TP-negative tumors with regard to clinical stage (P = 0.035). TP-positive tumors had significantly higher microvessel density (27.6 +/- 10.1) than TP-negative tumors (20.4 +/- 10.0, P = 0.01). Moreover, TP expression was significantly correlated with a poor prognosis (P = 0. 02). These suggest that in carcinoma of the papilla of Vater, TP production by tumor cells is correlated with tumor progression through its regulatory effect on neovascularization.

Adult↗

A case of pancreatic carcinoma with marked ductal dilatation: what contributed to the dilatation?

BACKGROUND: We report the case of an 82-yr-old man with invasive ductal carcinoma of the pancreatic head, in which the main pancreatic duct and duct of Santorini were markedly dilated, measuring 1.6 and 1.1 cm, respectively, in diameter on computed tomography. METHODS: A preoperative diagnosis of ductal carcinoma of the pancreatic head was made, and Whipple's procedure was carried out. RESULTS: Histopathologically, the tumor was diagnosed as moderately differentiated tubular adenocarcinoma, and the resected pancreatic parenchyma showed low papillary mucous cell hyperplasia and atypical hyperplasia in dilated ductular branches. Conclusion. Even among patients with tubular adenocarcinoma, the most common type of pancreatic ductal carcinoma, if the patient is aged and has chronic pancreatitis, the main pancreatic duct and duct of Santorini may dilate to the same degree as in mucin-hypersecreting neoplasm.

Adenocarcinoma↗

Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma.

Matrix metalloproteinases (MMP) play an important role in tumor cell invasion and metastasis. We examined the expression of MMPs in hepatocellular carcinoma (HCC) to determine whether they may help indicate the progression of HCC and patient outcome. The expression of MMP-1, -2, -7, -9, and MT1-MMP were determined in 37 pairs of HCC and adjacent non-tumor tissue specimens by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The tumor to non-tumor (T/N) ratios for mRNA expression of each MMP were compared with the clinicopathological findings and two-year disease-free survival rates. Immunohistochemical analysis for MMP-1 and -9 was performed in 30 specimens. MMP-1 and -9 expression was significantly higher in tumor tissue than in non-tumor tissue (p=0.001 and 0.0078, respectively). By contrast, the expression of MMP-2 and -7 was significantly lower in tumor tissue than in non-tumor tissue (p=0. 003 and 0.03, respectively). A higher MMP-9 T/N ratio was significantly associated with small HCCs (</=2 cm) and higher serum AFP values (>/=20 ng/ml) (p=0.013 and 0.028, respectively). Immunohistochemical analysis suggested that well differentiated HCC showed stronger immunoreactivity for MMP-9 than moderately differentiated HCC. MMP T/N ratio was not significantly associated with the disease-free survival rates. Overexpression of MMP-9 mRNA (T/N ratio >/=2) may be associated with the progression of small HCC (</=2 cm).

Adult↗

[A note form chair person: International Symposium on transplantation].

Orthotopic liver transplantation is now a widely accepted surgical modality for end-stage liver disease, although the shortage of grafts has remained a serious medical and social problem. This has led to the development of new approaches such as split liver transplantation and living related-donor liver transplantation, which have not completely resolved the problem. It is expected that future techniques will rely on better and less toxic agents for preventing rejection, xenotransplantation, and "organ engineering" methods based on tissue engineering techniques. More research is required before xenotransplantation is established clinically due to the current lack of knowledge of physiology, immunology, and infection risks. The mechanism of hyperacute rejection has been the subject of intensive investigation and is gradually being clarified. However, the detailed mechanisms of delayed xengraft rejection and cell-mediated immune response are still poorly understood. Improvement of cell culture conditions in tissue engineering may permit the generation of human organs as substitutes for grafts in the transplantation setting.

Animals↗

Overexpression of retinoblastoma protein predicts decreased survival and correlates with loss of p16INK4 protein in gallbladder carcinomas.

This study was designed to determine whether the level of retinoblastoma protein (pRb) expression predicts tumor progression and prognosis in gallbladder carcinomas (GBCs) and the relationship between pRb and pl6INK4 protein expression. The expression of these two proteins was evaluated immunohistochemically in 37 tumors from 36 patients with GBC. pRb loss and overexpression were observed in 5 (13.5%) and 18 (48.6%) of the 37 tumors, respectively. Both pRb loss and overexpression were significantly correlated with advanced TNM stage, lymph node metastasis, and tumor perineural invasion. Moreover, pRb overexpression was significantly associated with decreased overall survival (P = 0.001; log-rank test). Further analysis indicated that the influence of pRb overexpression on survival was independent of TNM stage and lymph node metastasis. Loss of p16INK4 protein was observed in 28 of the 37 GBCs (75.7%), but was not significantly associated with any clinicopathological factors or survival. pRb overexpression was significantly associated with the loss of p161NK4 protein (P < 0.0001). These results suggest that pRb overexpression significantly predicts decreased survival in GBCs.

Aged↗