Biomedical subjects

N Koide

Publications and source records attributed to N Koide.

195 records · Page 11Linked to original sources

PubMedDate not supplied

Basaloid squamous carcinoma of the esophagus with analysis by in situ nick end labeling and PCNA immunostaining.

BACKGROUND/AIMS: Basaloid squamous carcinoma (BSC) of the esophagus has been associated with poor outcome after surgery. In this study, apoptosis and cell proliferation of BSC were studied to evaluate the malignant potential of this cancer. METHODOLOGY: In tissue samples from 4 out of 5 BSC patients (1 patient with pre-operative radiotherapy was excluded) and from 30 patients with squamous cell carcinomas (SCCs) of the esophagus, apoptosis was studied by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and cell proliferation was evaluated by the immunostaining of proliferating cell nuclear antigen (PCNA). Two of the 5 patients with BSC died of recurrence and the remaining 2 patients are alive without recurrence. RESULTS: TUNEL-positive cells and PCNA-positive cells were observed to exist randomly and independently in the BSC samples. In the well- and moderately differentiated SCCs, TUNEL-positive cells and PCNA-positive cells were locally observed. The apoptotic index was significantly lower in the BSC than in the SCC tissues, and the PCNA labeling index was significantly higher in BSC than in SCC. CONCLUSIONS: These results suggest that BSC of the esophagus has great proliferative activity and weak apoptosis. These characteristics may reflect the aggressive behavior and poor prognosis of esophageal BSC. Early detection of this tumor, as in the present 2 cases, will contribute to a better prognosis.

Aged↗

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Immunohistochemical expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in squamous cell carcinoma of the esophagus.

BACKGROUND/AIMS: Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor which is an angiogenic factor. We attempted to clarify the significance of dThdPase expression in esophageal squamous cell carcinoma (SCC). METHODOLOGY: Tissues samples were taken from 50 patients with esophageal SCC after curative surgery. The expression of dThdPase was immunohistochemically examined using a monoclonal antibody to dThdPase (clone 654-1). Microvessels in SCC stained for Factor VIII-related antigen were counted. Vascular endothelial growth factor (VEGF) was immunostained with R11. Ki-67 antigen was immunostained with MIB-1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed, and Ki-67 labeling index (LI) and apoptotic index were calculated. RESULTS: The expression of dThdPase was observed in 30 patients (60%). Between the SCC with and without dThdPase expression, significant differences were found in microvessel count (p < 0.001) and VEGF expression (p < 0.01), but not in Ki-67 LI and apoptotic index. With regard to the clinicopathologic factors, significant differences were observed in histologic venous invasion (p < 0.01) and lymph node metastasis (p < 0.05). Survival rate after surgery was better in the patients with dThdPase-negative SCC (p < 0.05), and distant organ metastasis after surgery was frequently observed in the patients with dThdPase-positive SCC (p < 0.05). CONCLUSIONS: These results suggest that dThdPase expression may be associated with angiogenic promotion and may be one of the prognostic factors in esophageal SCC.

Apoptosis↗

PubMedDate not supplied

Histochemical study of vascular endothelial growth factor in squamous cell carcinoma of the esophagus.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of this study was to clarify the significance of VEGF expression in esophageal squamous cell carcinoma (SCC). METHODOLOGY: Tissues samples were taken from 52 patients with esophageal SCC after surgery. VEGF expression in these SCCs was examined immunohistochemically. Microvessels in the tumor stained for Factor VIII-related antigen were counted. Ki-67 antigen as a proliferative marker was immunostained with MIB-1, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed for the evaluation of apoptosis. Ki-67 labeling index (LI) and apoptotic index were then calculated. RESULTS: VEGF expression was observed in 30 of the patients (57.7%). The microvessel count was significantly higher (p = 0.007), and the apoptotic index was significantly lower (p < 0.0001) in the SCC with VEGF expression than in the SCC without it, but no significant difference was observed in the Ki-67 LI between these groups. There was an inverse correlation between the microvessel count and the apoptotic index (p = 0.007). In the clinicopathologic factors, histologic venous invasion of cancer cells (p = 0.039) and lymph node metastasis (p = 0.049) were significantly correlated with VEGF expression. The survival rate after curative surgery was better in the patients without VEGF expression (p < 0.05), and distant organ metastasis after surgery was frequently observed in the patients with VEGF expression (p = 0.023). CONCLUSIONS: These results suggest that VEGF expression is associated with angiogenesis in esophageal SCC, and may be a prognostic factor in patients with esophageal SCC. Furthermore, apoptosis may be influenced by angiogenesis in esophageal SCC.

Aged↗

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Risk factors associated with intra-operative blood loss in hepatectomized patients with giant cavernous hemangioma of the liver.

BACKGROUND/AIMS: The aim of this study was to clarify risk factors associated with intra-operative blood loss in hepatectomized patients with giant cavernous hemangioma (GCH) of the liver. METHODOLOGY: Twenty patients with GCH of the liver were treated by hepatectomy. Eleven patients with intra-operative blood loss > 2000 ml (mean: 7145 +/- 7080 m; Group 1) were reviewed retrospectively and compared to 9 patients with intra-operative hemorrhage < 2000 ml (mean: 918 +/- 429 ml; Group 2). RESULTS: Although there were no significant differences in pre-operative AST, ALT, and ICG-15 or fibrinogen and platelets between the two groups, pre-operative total bilirubin and fibrin degradation product (FDP) in Group 1 was significantly higher than in Group 2. Mean operation time and intra-operative blood transfusion in Group 1 versus Group 2 were 433 min vs. 213 min (p < 0.0001) and 3036 ml vs. 422 ml (p = 0.0072), respectively. The weight of resected liver (r = 0.821, p < 0.0001), maximum diameter of tumor (r = 0.782, p < 0.0001) and operation time (r = 0.748, p < 0.0001) were the most highly correlated with intra-operative blood loss, followed by pre-operative total bilirubin (r = 0.605, p = 0.0038), FDP level (r = 0.576, p = 0.0068) and intra-operative blood transfusion (r = 0.561, p = 0.0089). CONCLUSIONS: These findings suggest that pre-operative management to reduce the tumor size, total bilirubin and FDP levels may be essential to minimize intra-operative hemorrhage and blood transfusion.

Adult↗

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Effective treatment with chemotherapy and surgical resection for small cell carcinoma of the esophagus: report of a case.

We report on a patient with small cell carcinoma of the esophagus treated with effective combination chemotherapy followed by surgical resection. A 69 year-old male had an ulcerated tumor in the middle part of the esophagus, which was microscopically diagnosed as small cell carcinoma of the esophagus. After combination chemotherapy, endoscopy showed that the esophageal tumor had changed into a shallow ulcer. No cancer cell was found in the biopsy specimen of the ulcer. A subtotal esophagectomy with regional lymph node dissection was performed. Histological examination showed that a few cancer cells remained in a microvessel of the submucosal layer in the removed esophagus and no cancerous lesion was found in regional lymph nodes. The patient was well and was able to remain at home. However, he eventually died 21 months after first detection of the carcinoma due to progression of multiple lung and mediastinal lymph node metastases. After complete or partial remission is achieved by the combination chemotherapy, surgical resection may be recommended as the second therapy that occasionally produces long-term remission and possibly long-term survival for patients with small cell carcinoma of the esophagus, such as the present case.

Aged↗

PubMedDate not supplied

Synchronous gastric cancer associated with hepatocellular carcinoma: a study of 10 patients.

BACKGROUND/AIMS: Little information regarding synchronous gastric cancer (GC) associated with hepatocellular carcinoma (HCC) is available. The aim of this study was to clarify the clinicopathologic features of synchronous GC associated with HCC, and we also discuss the diagnostic and therapeutic issues regarding them. METHODOLOGY: In a series of 396 patients with GC and 340 patients with HCC, we investigated the clinicopathologic features of the patients with synchronous GC associated with HCC (HCC group; n=10). They were compared to the patients with resected GC without HCC (non-HCC group) which was divided into 2 groups: with chronic hepatic disease (CHD: CHD group; n=15) and without CHD (Control group; n=345). RESULTS: The HCC group consisted of 10 of the 396 patients with GC (2.6%), and of 340 with HCC (2.9%). Eight node-negative early GC and 2 advanced GC cases were observed in the HCC group. Nine of these GC (90%) were well-differentiated adenocarcinoma. The tumor sizes of the HCC group were significantly smaller than those of the control group (p<0.05). The incidences of intestinal type and early GC in the HCC group were significantly higher than those in the control group, (p<0.05). However, there were no significant differences in any parameters between the HCC group and CHD group. With regard to early GC, there were no significant differences in any parameters, excluding the site of GC in the CHD group, between the HCC group and non-HCC group. Eight in the HCC group were surgically resected, and the post-operative period of these patients was uneventful. Although there were no significant differences in survival after surgery among the 3 groups, the survival of the patients with early GC in the HCC group was significantly worse than that in the control group (p<0.01). CONCLUSIONS: The clinicopathologic features of synchronous GC associated with HCC are not very aggressive in most patients probably because of the early detection, and those of early GC with HCC appeared to resemble that of GC with CHD. Since early GC may not influence the clinical outcome of HCC patients, limited gastric resection can be recommended even when curative surgery for HCC is performed. By contrast, when advanced GC is present, curative gastrectomy with lymphadenectomy would be advisable to improve the long-term survival.

Adenocarcinoma↗

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Expression of the midkine gene in human hepatocellular carcinomas.

BACKGROUND/AIMS: Aberrant expression of Midkine (MK) has been found in various human carcinomas including hepatocellular carcinoma (HCC). The aim of study is to identify the incidence of MK expression in tumor and surrounding non-tumor tissues of the liver, and to find the correlation of MK expression with other tumor markers. METHODOLOGY: Liver tissues were obtained from 16 patients with HCC and 4 with metastatic liver cancer. Background diseases of the HCC patients include liver cirrhosis and chronic hepatitis of type B or C. RNA was prepared from both cancerous and surrounding non-cancerous tissues, and analyzed for the presence of MK mRNA by RT-PCR, PCR-Southern blot, and Northern blot analysis. RESULTS: MK expression was detected in 12 (75%) of 16 HCCs by PCR-Southern blot analysis, the most sensitive of the 3 methods. Three of 9 surrounding cirrhotic tissues were weakly positive for MK expression, and none of chronic hepatitis and 4 normal tissues were negative. No significant difference was found in clinical and pathological parameters between MK negative and positive cases. Among metastatic cancers, 1 of gastric origin was positive for MK expression, but 1 each of chorangiocellular, gall bladder, and gastrinoma origin was negative. CONCLUSIONS: These results suggest that MK is expressed in the majority of HCC tissues and rarely in surrounding tissues in chronic liver diseases.

Aged↗

PubMedDate not supplied

Effects of prostaglandin E1 administration during hepatectomy for cirrhotic hepatocellular carcinoma.

BACKGROUND/AIMS: Prostaglandin E1 has been used in hepatectomy based on a few limited clinical studies suggesting that PGE1 improves liver function. The aim of this study was to evaluate the effects of PGE1 administration during hepatectomy for cirrhotic hepatocellular carcinoma. METHODOLOGY: Forty-three patients undergoing hepatectomy for cirrhotic hepatocellular carcinoma were divided into 2 groups: hepatectomy with Prostaglandin E1 treatment (PG group; n = 19) and without Prostaglandin E1 treatment (control group; n = 24). Prostaglandin E1 (0.02-0.07 microgram/kg/min) was administered intravenously from beginning to end of surgery in the PG group. RESULTS: There were no significant differences between groups with respect to age, gender, preoperative liver and renal function, or intraoperative variables such as blood loss, weight of resected liver and total clamping time by the Pringle maneuver. No patient had severe postoperative complications. Initial postoperative maximum concentrations of serum total bilirubin, creatinine, and blood urea nitrogen in the PG group were significantly lower than those in the control group. CONCLUSIONS: Prostaglandin E1 administration during hepatectomy for cirrhotic heptocellular carcinoma resulted in improved renal and hepatic function.

Aged↗

PubMedDate not supplied

Cytokine response to human liver ischemia-reperfusion injury during hepatectomy: marker of injury or surgical stress?

BACKGROUND/AIMS: The aim of this study was to evaluate the inflammatory or antiinflammatory cytokine response to ischemia-reperfusion during hepatectomy and to find a useful marker of injury or surgical stress during hepatic ischemia-reperfusion. METHODOLOGY: In 9 patients with liver disease who underwent hepatectomy using the Pringle maneuver, serum cytokines, including alanine transaminase, aspartate transaminase, and hyaluronic acid, were measured just prior to vascular occlusion; 5, 10 and 15 min after initial clamping; and 3 min after initial declamping. RESULTS: The mean concentrations of aspartate transaminase and alanine transaminase did not significantly differ before and after ischemia-reperfusion during hepatectomy. However, mean concentrations of hyaluronic acid after ischemia-reperfusion were significantly (P < 0.03) higher than before clamping. Although there were no significant differences in the mean concentrations of IL-1 beta, IL-6, IL-8, IL-10 and TNF-alpha among, before and after ischemia-reperfusion, the mean concentrations of granulocyte colony-stimulating factor after ischemia-reperfusion and macrophage colony-stimulating factor after reperfusion were significantly (P < 0.05) higher than before clamping. CONCLUSIONS: Although hepatic parenchymal cell function was maintained after ischemia-reperfusion during hepatectomy, sinusoidal endothelial cell dysfunction was found. Release of granulocyte colony-stimulating factor and macrophage colony-stimulating factor after ischemia-reperfusion were also found. These cytokines and hyaluronic acid may be useful indicators in the early phase of human ischemia-reperfusion injury during hepatectomy.

Aged↗

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Portal vein thrombosis associated with hilar bile duct carcinoma and liver abscess.

As most portal vein occlusion in hilar bile duct carcinoma is caused by tumor invasion to the portal vein, other mechanisms of its occlusion are very rare. We report the case of a 69-year-old man who underwent surgical resection for an advanced hilar bile duct carcinoma associated with unusual portal vein occlusion. Preoperative diagnosis was advanced hilar bile duct carcinoma with liver abscess and right portal vein occlusion due to tumor invasion. Extended right hepatectomy combined with resection of caudate lobe was performed. Intraoperatively, tumor invasion to the portal vein was not evident and resected margin of the right portal vein showed thrombosis and no evidence of malignancy histologically. To our knowledge, this is the first reported case of a patient with a combination of portal vein thrombosis and liver abscess in hilar bile duct carcinoma. Although portal vein occlusion due to thrombosis is an unusual complication in hilar bile duct carcinoma, the presence of liver abscess may be a useful diagnostic implication of this occlusion.

Aged↗

PubMedDate not supplied

Detection of hepatitis C virus RNA in circulating immune complexes by RT-PCR.

BACKGROUND/AIMS: We investigate whether hepatitis C virus (HCV) forms a circulating immune complex (CIC) in patients with chronic HCV infection. MATERIALS AND METHODS: We examined HCV-RNA immunoprecipitated with anti-human IgG, A and M antibodies by reverse transcription-polymerase chain reaction. RESULTS: In thirty-nine (91%) of 43 patients, composed of 35 chronic hepatitis (CH) and 8 liver cirrhosis (LC), HCV-RNA was detected in the CIC. All 43 patients analyzed were classified into the following three categories; HCV-RNA was detected only in the supernatant (S pattern, 4 patients), both in the supernatant and the precipitate (SP pattern, 27 patients), and only in the precipitate (P pattern, 12 patients). SP pattern was most common in chronic HCV infection, and the frequency of SP pattern decreased with the progression of liver disease. P pattern was significantly more frequent in patients with higher gamma-globulin levels, histologically indicated LC, and antibody to HCV envelope protein. CONCLUSION: We found that HCV formed a CIC in most patients with chronic HCV infection, and that the formation of CIC might be related to the stage of chronic HCV infection.

Antigen-Antibody Complex↗

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Promoter-independent loss of mRNA and protein of the Rb gene in a human hepatocellular carcinoma.

BACKGROUND: Inactivation of the retinoblastoma (Rb) gene is considered to play a fundamental role in the genesis and progression of several human cancers. In retinoblastoma, the inactivation of Rb promoter by mutations or hypermethylation has been reported. Although genetic changes of Rb gene have been described in hepatocellular carcinoma (HCC), an epigenetic change such as hypermethylation of the Rb promoter as reported in retinoblastoma has not been described. MATERIALS AND METHODS: We examined the hypermethylation in the promoter region of Rb gene by restriction fragment length polymorphism in 19 HCCs, as well as the expression of Rb mRNA and protein by RT-PCR and by immunoblotting, respectively. RESULTS: We found no evidence of hypermethylation in the promoter region of the Rb gene in all HCCs analyzed. However, the expression of Rb mRNA and protein was lost in one HCC, and no mutation was detected in the Rb promoter region of this patient. The inactivation of Rb promoter by hypermethylation or by inhibition of binding of transcription factors due to point mutations did not contribute to the loss of mRNA and protein in the patient. CONCLUSIONS: Hypermethylation in the Rb promoter region appeared to have little causal effect on HCC.

Aged↗

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Reciprocal gene expression of rat fibroglycan and beta-actin during the course of regeneration after D-galactosamine liver injury.

BACKGROUND/AIMS: Fibroglycan (FG) is a major heparan sulfate proteoglycan (HSPG) in the rat liver that is mainly distributed on the surface of hepatocytes. HSPG may play some important roles in the regeneration of liver by interacting with various growth factors such as bFGF and HB-EGF. However, little is known about the function of FG. We reported that after injury caused by D-galactosamine, regeneration started on the following day and peaked on day 2. To clarify the function of FG in liver regeneration, we investigated the gene expression of FG during regeneration after D-galactosamine injury. MATERIALS AND METHODS: Rats were given D-galactosamine on day 0. Liver RNA was collected from day 0 to day 7. The gene expression of FG and beta-actin (as a representative cytoskeleton) was examined by Northern and/or Slot blotting. RESULTS: FG gene expression was markedly decreased on day 2, but totally recovered on day 3. In contrast, beta-actin gene expression was markedly increased on day 2 and returned to the normal level on day 3. Expression of the FG and beta-actin genes was reciprocal. CONCLUSION: FG expression is transiently suppressed when cytoskeleton gene expression is enhanced at the early phase of liver regeneration.

Actins↗

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Point mutations in the S and pre-S2 genes observed in two hepatitis B virus carriers positive for antibody to hepatitis B surface antigen.

Two hepatitis B virus (HBV) carriers who had antibodies to HBV surface antigen (anti-HBs) were studied. Case 1 was a 47 year old woman positive for hepatitis B e antigen (HBeAg), and case 2 was a 61 year old man positive for antibody to HBeAg (anti-HBe) and DNA-polymerase (DNA-p). Neither case had received the HBV vaccine. The nucleotide sequences of the HBV-DNA extracted from the patients' sera were determined within the pre-S2 and S genes. Seven out of nine S gene clones from case 1 and six out of nine S gene clones from case 2 had an amino acid replacement from Thr or Ile to Ser at codon 126 in the alpha-determinant of the S gene. Amino acid substitution of codon 145 of the S gene previously reported was not observed. Although two previous reports on HBV escape mutant carriers with both anti-HBs and HBeAg described some deletions in the pre-S2 gene, our cases did not show these deletions. Our analysis indicated that carriers with the HBV escape mutant did not always have pre-S2 gene deletions. We found two HBV escape mutant carriers who had amino acid substitutions at codon 126 in the S gene due to point mutation without any deletions in the pre-S2 gene.

DNA, Viral↗

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Two cases of gastric involvement of esophageal cancer: intramural metastasis and intramural lymph node metastasis.

Cases of esophageal cancer with intramural metastasis to the stomach and esophageal cancer with metastasis to an intramural lymph node of the stomach are herein reported. The former patient was a 52 year-old male. Squamous cell carcinoma (SCC) of the lower esophagus with an intramural metastasis located at the gastric cardia and a small leiomyoma at the fornix were resected. The latter patient was a 70 year-old female. SCC of the lower esophagus and an intramural lymph node metastasis located at the anterior wall of the gastric cardia were resected. The patient died nevertheless of multiple liver metastases. These gastric involvements were detectable by endoscopy before surgery. The clinicopathological features of these esophageal cancers were characterized; the sites were the lower part of the esophagus, and extreme lymphatic and vascular invasions were shown histologically. The gastric tumors were located in the upper third of the stomach, and the findings revealed submucosal tumors. It is therefore important to discriminate other gastric tumors, and to resect them simultaneously with esophageal cancer when a gastric tube has been used for reconstruction after esophagectomy.

Aged↗