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Biomedical subjects

N Nagasue

Publications and source records attributed to N Nagasue.

At least 19 recordsLinked to original sources
PubMed2003

Prognostic significance of metastatic lymph node size in patients with gastric cancer.

BACKGROUND: Patients with gastric cancer that has metastasized to the lymph nodes are a heterogeneous population with a variable prognosis. Stratification of these patients into prognostic groups is necessary for optimal adjuvant therapy. METHODS: The study comprised 715 patients who had undergone curative resection of a gastric neoplasm. Lymph nodes were sectioned, stained with haematoxylin and eosin, and the diameter of the largest metastatic lymph node (MLN) was measured. Patients with metastatic nodes were divided into groups n1 and n2 according to the size of the MLN. The cut-off level was set at 7 mm by a two-sample log rank test; patients in group n1 had a MLN size of 7 mm or less and those in group n2 had a MLN of 8 mm or more. RESULTS: Patients were stratified into significant prognostic groups by both the Union International Contra la Cancrum (UICC) node (N) stage and MLN size (n group). The UICC N-stage subcategories were further divided into prognostic groups according to MLN size (n group). On multivariate analysis the MLN size remained independently significant in terms of overall and disease-free survival rates, and the UICC N stage was not significant, independently of the n group. Node-positive patients with fewer than 15 lymph nodes removed at operation could also be stratified into prognostic groups by the n group. Stratification according to the TNM stage and by MLN size was superior to existing UICC TNM staging. CONCLUSION: This new method may help clinicians to design a more appropriate treatment strategy for patients with gastric cancer.

Adult↗
PubMed2003

Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences. Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.

Aged↗
PubMed2002

Impact of splenectomy on the early outcome after oesophagectomy for squamous cell carcinoma of the oesophagus.

AIM: Operative procedures for oesophageal malignancies are becoming more extensive and may result in fatal complications. Splenectomy compromises the immune system and can lead to increased susceptibility to infections. The aim of the present study was to report the early outcome of patients who underwent oesophagectomy and simultaneous splenectomy due to oesophageal squamous cell carcinoma (SCC). METHODS: Pre-operative risks and post-operative morbidity and mortality in 135 patients who had undergone extensive oesophagectomy without simultaneous splenectomy for SCC of the thoracic oesophagus were compared with those of 14 patients who had undergone oesophagectomy associated with splenectomy. RESULTS: Post-operative pneumonia, intra-abdominal abscess, post-operative sepsis and anastonotic leakage were significantly increased when splenectomy was added to the original operation. The incidence of in-hospital death was significantly higher among splenectomized than non-splenectomized patients (35.7% vs 8.1%, P<0.01). Pulmonary complications and leakage were the main causes of death. Multivariate analysis recognized splenectomy as an independent prognostic factor for in-hospital death following transthoracic oesophagectomy for SCC. CONCLUSION: The addition of splenectomy to transthoracic oesophagectomy for oesophageal carcinoma can be a fatal combination. Preservation of the spleen should be the primary intention. In circumstances that necessitate splenectomy precautions should be taken to prevent post-operative infectious complications.

Carcinoma, Squamous Cell↗
PubMed2001

Peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition of human hepatocellular carcinoma.

Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been implicated in the growth inhibition and differentiation of certain human cancers with diverse tissue origin. In this study, expression of PPARgamma in human hepatocellular carcinoma (HCC) and the effect of PPARgamma ligands on HCC cells were investigated in vitro using Hep G2, HuH-7, KYN-1 and KYN-2 cell lines. All cell lines were found to express functionally active PPARgamma and a marked growth inhibition was induced by thiazolidinedione ligands troglitazone, and pioglitazone as well as with its natural ligand 15-deoxy-Delta(12,14)-prostaglandin J(2). The growth inhibitory effect was associated with a dose-dependent inhibition of DNA synthesis, cell cycle progression and alpha fetoprotein expression.

Carcinoma, Hepatocellular↗
PubMed2001

Adjuvant chemotherapy after resection of hepatocellular carcinoma causes deterioration of long-term prognosis in cirrhotic patients: metaanalysis of three randomized controlled trials.

BACKGROUND: The goal of the current study was use metaanalysis to evaluate the effect of postoperative adjuvant chemotherapy after resection of hepatocellular carcinoma (HCC), especially in cirrhotic patients. METHODS: One hundred-eight patients with radical resection of HCC were included in 1 of 3 prospective randomized control studies that used different postoperative chemotherapy protocols. Fifty-one patients underwent resection alone, and 57 patients received postoperative adjuvant chemotherapy. The first protocol was intraarterial epirubicin (40 mg/m(2)) at 1 month after surgery followed by oral tegafur (300 mg/day) for 1 year. The second protocol was intraarterial epirubicin (40 mg/m(2)) at 1 month after resection followed by intravenous epirubicin (40 mg/m(2)) every 3 months for 2 years. Additionally, carmofur 300 mg/day was administered for 2 years. The third protocol was intravenous epirubicin (40 mg/m(2)) every 2 months starting 1 month after surgery for 1 year. RESULTS: There were no significant differences in clinicopathologic background in each of the three protocols between the groups with and without chemotherapy. Postoperative chemotherapy using the current protocols failed to improve patient outcome in all patients and failed to improve disease-free and overall survival in any patients who were included in individual protocols. In patients with cirrhosis, postoperative chemotherapy was associated with significantly worse disease-free (P = 0.0376) and overall survival rates (P = 0.0077). CONCLUSIONS: The current study indicated that cancer recurrence in the remnant liver is enhanced and the long-term outcome is deteriorated by postoperative chemotherapy after resection of HCC in cirrhotic patients.

Antibiotics, Antineoplastic↗
PubMed2001

Androgen metabolism in regenerating liver of male rats: evidence for active uptake and utilization of testosterone.

The role of androgen in the regenerative process of the liver remains unclear. Male Sprague-Dawley rats were subjected to either 70% hepatectomy or sham operation. Immediately after surgical procedures, rats were injected with 0.3 µCi/g of body weight [3H]-testosterone from the inferior vena cava. The radioactivities of the remnant liver were counted for 0-24 h. For measurement of sex hormones and their metabolizing enzymes activities in the regenerating liver, the same experiments were also conducted, in which the rats were sacrificed up to 120 h. The plasma and hepatic testosterone, dihydrotestosterone(DHT) and estradiol were determined by radioimmunoassays. Uptake of [3H]-testosterone in the regenerating liver was significantly higher during the first 6 h. 5alpha-reductase I and DHT were increased in parallel to the hepatocyte proliferation which was assessed by proliferating cell nuclear antigen (PCNA) labeling index. On the other hand, hepatic 3alpha-hydroxysteroid dehydrogenase level did not alter but aromatase activity significantly decreased after 70% hepatectomy. These results suggest that during the early phase of liver regeneration, testosterone was actively uptaken from the plasma by the regenerating liver and was converted into DHT by elevated hepatic 5alpha-reductase enzyme. Thus androgens might play a crucial role in liver regeneration.

Journal Article↗
PubMed2001

Prognosis of T4 gastric carcinoma patients: an appraisal of aggressive surgical treatment.

BACKGROUND AND OBJECTIVES: Despite precipitous drop in the incidence of gastric carcinoma in Japan, it is still one of the leading causes of death associated with malignant disease. Once the contiguous organs are involved the prognosis becomes dismal. Prognostic factors governing the survival of patients with T4 gastric carcinoma remain unclear. METHODS: Between 1980 and 1998, 150 patients were treated for T4 gastric carcinoma. Results and prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: With a 73% resectability, patients with tumor resection had a significantly (P < 0.0001) improved survival rate. Within an acceptable operative mortality (2.6%), apparently curative cases had survival benefit (P < 0.0001) over noncurative cases. In the multivariate analysis, the death risk increased by 2.18 (relative risk) when splenectomy was spared from the operative procedure (P < 0.0071). Presence of esophageal invasion was the other independent prognostic factor in T4 gastric carcinoma patients (relative risk 2.11). Conventional prognostic factors along with the type of organs invaded by the carcinoma had no impact on prognosis. CONCLUSIONS: Patients with T4 gastric carcinoma might be benefited from aggressive surgery with a curative intent. Whenever possible, splenectomy should be done along with invaded organ resection.

Adult↗
PubMed2001

Enhanced apoptosis and transforming growth factor-beta1 expression in colorectal adenomas and carcinomas after Sulindac therapy.

PURPOSE: We tried to elucidate the effects of sulindac on human colorectal carcinoma. METHODS: Sulindac (300 mg/day) was administered for two weeks before operation to 33 patients with sporadic colorectal carcinoma (Sulindac Group). Resected specimens were used to detect apoptosis by terminal dUTP nick end labeling and transforming growth factor (TGF)-beta1 expression by immunohistochemistry. The results were compared with those from the historical Control Group. Twenty-nine available preoperative biopsies taken from carcinomas before sulindac prescription and 22 concurrent colorectal adenomas (9 and 13 in Sulindac and Control Groups, respectively) in the resected specimen were also examined regarding TGF-beta1 expression. RESULTS: In the resected carcinomas and adenomas, more frequent apoptosis and higher TGF-beta1 scores were observed in the Sulindac Group than in the Control Group. Overexpression of TGF-beta1 and apoptosis occurred in the same region in adenomas but not in carcinomas. A positive correlation between TGF-beta1 scores and apoptotic frequency was found in adenomas (P = 0.01, rho = 0.91) but not in carcinomas (P = 0.89, rho = 0.03). CONCLUSION: We conclude that sulindac induces apoptosis in human colorectal carcinomas as well as in adenomas. Also, one of the antineoplastic effects of sulindac might be mediated by upregulating TGF-beta1 expression, particularly in colorectal adenomas.

Adenoma↗
PubMed2001

Dukes' classification as a useful staging system in resectable squamous cell carcinoma of the esophagus.

Dukes' classification for colorectal cancer is simple and has been widely used as a valuable prognostic indicator. It has been used as an assessment of gastric cancer, but it has not been evaluated for esophageal cancer. Of 251 patients with primary squamous cell carcinoma of the thoracic esophagus between February 1981 and April 1999, 155 patients underwent esophagectomy with a curative intent. Clinicopathologic characteristics of those 155 patients were retrospectively investigated according to the Dukes', tumor node metastasis (TNM) and Japanese staging systems. Dukes' classification showed a clear correlation between tumor stage and survival. The 3-year and 5-year survival rates of 64 Dukes' A cases were excellent (97.4% and 93.7%), good for 12 Dukes' B (75% and 75%), and poor for 79 Dukes' C (50.5% and 43.4%), respectively (P < 0.05; Dukes' A vs B, P < 0.0001; Dukes' A vs C, P < 0.10; Dukes' B vs C). TNM stage classification also showed a good correlation between tumor stage and survival, but there were no significant differences between stage 0, I and stage IIA cases (P = 0.2678) and between stage III and stage IV cases (P = 0.8298). In the Japanese staging system, there were no significant differences among stage 0, stage 1, and stage 2 cases (P = 0.4093). Dukes' classification was significantly correlated with tumor size, Borrmann type, histological type, and vessel invasion. Subdivision of Dukes' C according to the number of positive lymph nodes (1-4 vs > or = 5) showed a clearer correlation with survival rather than other subdivisions, such as the metastatic lymph node ratio (< 1.0 vs > 1.0) or the site of lymph node metastasis. Dukes' classification, which incorporates the number of positive lymph nodes, correlates well with tumor progression and provides a simple useful staging system after curative esophagectomy for esophageal cancer. Dukes' A tumor could be proposed as a criterion of early esophageal carcinoma.

Aged↗
PubMed2001

Esophagectomy and hepatic arterial chemotherapy following hepatic resection for esophageal cancer with liver metastasis.

We report a patient who had simultaneous transthoracic esophagectomy and hepatic arterial cannulation for chemotherapy following hepatic resection for esophageal cancer with solitary liver metastasis. He had an uneventful postoperative course and received two cycles of postoperative arterial chemotherapy with cisplatinum and 5-fluorouracil. He developed multiple liver metastases 6 months after the surgery. He has been receiving arterial chemotherapy at the outpatient department and is alive 15 months after the surgery. Aggressive esophagectomy and hepatic arterial chemotherapy is the treatment of choice for esophageal cancer with liver metastasis when unresectable metastases are confined to the liver.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Repeated hepatic dearterialization for unresectable carcinomas of the liver: report of a 10-year experience.

The effectiveness of repeated hepatic dearterialization (RHD) therapy was evaluated in 26 patients with unresectable primary and secondary liver tumors. RHD was performed in 12 patients with hepatocellular carcinoma (HCC), 7 with hepatic metastases from colorectal carcinoma, and 7 with hepatic metastases from gastric carcinoma. It was repeatedly carried out by occluding the hepatic artery for 1 h twice daily. All patients concurrently received an intra-arterial infusion of anticancer drugs. More than 50% remission of the hepatic tumors, defined as a partial response (PR), was demonstrated in 8 patients (31%). A higher PR was seen in hepatic tumors from metastatic gastric cancer (5 out of 7 patients; 71%). Most patients who suffered severe complications had HCC with liver cirrhosis. These preliminary results suggest that RHD with intra-arterial chemotherapy is an acceptable palliative treatment for patients with unresectable liver metastasis from gastric cancer; however, the majority of patients with HCC are not responsive to such treatment, primarily because most have underlying cirrhosis predisposing to the development of postoperative complications at an unacceptably high rate.

Aged↗
PubMed2001

Easier hepatic resections with a straight needle.

BACKGROUND: A stainless-sheathed, straight needle with a hook near the top of the inner needle was designed to facilitate hepatic resections. METHODS: First, using this needle, two rows of interlocking mattress sutures were made along the division line; then, hepatic transection was performed between these rows by electrocautery or forceps. RESULTS: Since 1997, we have performed this kind of hepatic resections in 43 cases, including 9 right lobectomies, 5 bisegmentectomies, 7 segmentectomies, 4 subsegmentectomies, 2 partial hepatectomies, 15 left lateral segmentectomies, and 1 hepatorrhaphy. In most cases, intraoperative hemorrhage was minimal. Neither specified inflow nor backflow control procedures were needed. CONCLUSION: Use of this needle may reduce the difficulty of the technique and blood loss for right hepatic lobectomy, left lateral segmentectomy, and some segmental or partial hepatectomy procedures.

Blood Loss, Surgical↗
PubMed2001

Esophageal resection in elderly esophageal carcinoma patients: improvement in postoperative complications.

BACKGROUND: Advanced age is considered to be a relative contraindication for radical esophagectomy with a three-field lymph node dissection. METHODS: Preoperative risks, postoperative morbidity and mortality, and long-term survival in 55 elderly patients (> or =70 years) who had undergone extensive esophagectomy for esophageal carcinoma were compared with those of 149 younger patients (<70 years). RESULTS: Elderly patients had worse preoperative cardiopulmonary function and had more frequent postoperative cardiopulmonary complications compared with younger patients (p < 0.05). The postoperative death rate was not statistically different between the elderly (10.9%) and younger groups (5.4%). When the study period was divided into an early and a late phase, the postoperative death rate dropped significantly (p < 0.05) in recent years (1.4%) when compared with the previous era (10.0%). The overall survival rates were not different between elderly and younger patients. CONCLUSIONS: Preoperative cardiopulmonary risk factors and postoperative complications after esophagectomy were more frequently noticed in elderly patients than in younger patients. A dramatic improvement in postoperative death was noticed in recent years. The long-term survival of elderly patients after extended esophagectomy was almost similar to that in younger patients.

Aged↗
PubMed2001

Sinusoidal endothelial cell proliferation and expression of angiopoietin/Tie family in regenerating rat liver.

BACKGROUND/AIMS: Angiogenesis is essential in liver regeneration. However, only little is known about sinusoidal endothelial cell proliferation and the role of different angiogenic growth factors and their receptors during regeneration. METHODS: Seventy percent hepatectomy was carried out on male rats. Serial changes in endothelial cell proliferation were evaluated by immunohistochemistry. The mRNA expressions of angiogenic growth factors (vascular endothelial growth factor (VEGF) and angiopoietins 1 and 2) and their receptors (flt-1, flk-1, Tie-1 and Tie-2) in the whole liver were evaluated by semi-quantitative RT-PCR. RESULTS: Significant elevation of endothelial cell proliferation started at 48 h and peaked at 72 h after hepatectomy. The ratio of sinusoids to liver tissue area initially decreased at 72 h, and thereafter, significantly increased at 96 h. VEGF related factors had early peaks, which coincided with the endothelial proliferation. flt-1, flk-1 and VEGF expressions peaked at 24, 48 and 72 h, respectively. angiopoietin/Tie factors peaked at 96 h, except Ang-2, which gradually increased and peaked at 168 h. CONCLUSIONS: During liver regeneration, hepatocyte proliferation was followed by endothelial cell proliferation. The VEGF family and angiopoietin/Tie system may have distinct roles in angiogenesis, with an enhanced expression of the VEGF family in the early phase of regeneration followed by angiopoietin/Tie expression.

Angiopoietin-1↗
PubMed2001

Clinicopathologic factors correlated with number of metastatic lymph nodes in oesophageal cancer.

BACKGROUND: The number of metastatic lymph nodes is applied to the staging system of gastric cancer and colorectal cancer. However, it has not been evaluated in oesophageal cancer. PATIENTS AND METHODS: Of 258 patients with primary squamous cell carcinoma of the thoracic oesophagus between February 1981 and December 1999, 160 underwent three-field oesophagectomy with a curative intent. Clinicopathologic characteristics of those 160 patients were retrospectively investigated according to the number of metastatic lymph nodes. RESULTS: Seventy-eight patients had no lymph node metastases and 82 (51.3%) had lymph node metastases; 51 [31.9%)] had between 1 and 4 positive lymph nodes, and 31 (19.4%) had > or =5. The number of metastatic lymph nodes was significantly correlated with tumour size, macroscopic classification, histological differentiation, pT, pN, and vessel invasions. Multivariate analysis showed that lymph vessel invasion (relative risk 12.6), histological differentiation (relative risk 4.2), and tumour size (relative risk 3.8) were independent factors correlated with number of metastatic lymph nodes. The number of metastatic lymph nodes was also well correlated with the Japanese nodal level and TNM stage, respectively (p<0.001). The 5-year disease-specific survival rate according to the number of positive lymph nodes was 90% for patients without lymph node metastases, 52.2% with 1-4, and 28.9% with > or =5, respectively, p<0. 0001; 0 vs 1-4, p<0.05; 1-4 vs > or =5). CONCLUSION: The number of positive lymph nodes is well correlated with tumour progression and provides a useful prognostic indicator after oesophagectomy for oesophageal cancer.

Aged↗
PubMed2001

Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis.

BACKGROUND: Detailed follow-up of patients with chronic hepatitis has resulted in increased diagnosis of hepatocellular carcinoma (HCC) in patients without cirrhosis. Despite numerous studies on hepatic resection, the prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. METHODS: Among 349 patients with HCC treated in the past 13 years, cirrhosis was absent in 126 patients (36 per cent). Curative hepatic resection was carried out in 100 (79 per cent) of these patients. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. RESULTS: Postoperative morbidity and mortality rates were 22 and 3 per cent respectively. The 5- and 10-year disease-free and overall survival rates were 31 and 50 per cent, and 22 and 47 per cent respectively. Blood loss, surgical resection margin, intrahepatic metastasis, portal vein invasion and extent of hepatic resection were independently associated with overall survival. However, the only risk factors for intrahepatic recurrence were portal vein invasion and hepatitis C virus (HCV) infection. The former was related to early recurrence while the latter was related to later recurrence. The 5-year disease-free survival rate was 58 per cent in patients with hepatitis B virus infection while it was 6 per cent in patients with HCV infection (P < 0.001). CONCLUSION: In the treatment of HCC without cirrhosis, major hepatectomy is advocated to prevent early recurrence. Liver transplantation may be required for patients with HCV infection.

Adult↗