Successful reconstruction using a proximal gastric tube for synchronous carcinomas of the esophagus and the stomach.
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Publications and source records attributed to K Sugimachi.
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Characteristics of multicentric hepatocellular carcinomas (HCCs) remain obscure. We therefore aimed to clarify them and compare them with HCC with intrahepatic metastases. A series of 118 patients who had definite hepatitis C viral status and multinodular HCC were divided into two groups: a multicentric occurrence (MO) group (n = 38), with multicentric HCCs; and an intrahepatic metastasis (IM) group (n = 80), with HCC having intrahepatic metastases. Clinicopathologic variables, including the patient's survival and disease-free survival rates, were compared between the MO and IM groups. Univariate analysis revealed the presence of esophageal varices, the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, hepaplastin test, gamma-globulin, the histologically active hepatitis, tumor size, des-gamma-carboxy prothrombin > 0.1 AU/ml, positive portal vein invasion, and histologic grade as discriminating factors. The MO score to differentiate multicentric HCCs from intrahepatic metastatic HCCs was determined using the following four independent factors selected by a stepwise regression analysis: the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, tumor size, and histologic grade. The sensitivity and specificity of the MO scores using those factors were 84% and 70%, respectively, when the cutoff value was 0.4. The disease-free survival rate in the MO group was similar to that in the IM group, whereas the survival rate in the MO group was significantly better than that in the IM group. The multivariate analysis revealed the multicentric occurrence of HCC as one of the independent prognostic factors. Clinicopathologic factors differentiating multicentric HCCs from intrahepatic metastatic HCCs were the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, small tumor size, and low histologic grade.
Hepatic resection has been regarded as a curative treatment for primary hepatocellular carcinoma (HCC), but a high incidence of postoperative recurrence is general. Thus it is important to predict the patterns of recurrence and select the appropriate treatment for recurrence for a better long-term prognosis of patients with HCC. Clinicopathological studies on 80 patients with intrahepatic recurrence after curative hepatectomy suggested that nodular-type recurrence with up to three nodules is mainly due to metachronous multicentric hepatocarcinogenesis rather than intrahepatic metastases. We reviewed 300 patients with recurrent HCC, and repeat hepatectomy was done in 78 cases (26.0%). The 3- and 5-year survival rates after repeat hepatectomy were 82.8% and 47.5%, respectively, showing better prognosis than those for other treatments. Repeat hepatectomy is the preferred treatment offering a hope of long-term survival for patients with recurrent HCC as long as liver function is sufficient; thus early detection of recurrence should be ensured.
To demonstrate recent experience of gastric cancer surgery worldwide and to evaluate modern strategies for the treatment of gastric cancer, we investigated the English-language literature of the past 10 years, based on papers published in well-known medical journals. In many countries, the increased detection of early gastric cancer, advanced operative procedures, and careful postoperative management have improved the surgical results of gastric cancer over the years. Although randomized controlled trials in Europe showed no survival benefit of D2 resection over D1 resection, the results must be interpreted with caution and cannot be extrapolated to Japanese patients, because the morbidity and mortality after D2 gastrectomy in Japan are much less than those after D1 gastrectomy in Europe. Recently, less invasive treatments, including endoscopic mucosal resection and laparoscopic gastrectomy, have become feasible for patients with early gastric cancer, but their risks and benefits compared with traditional gastrectomy are unclear.
The role of adjuvant chemotherapy in gastric cancer has been studied extensively over the past three decades in an attempt to further improve the prognosis of patients with gastric cancer who have undergone curative surgery. To date, no definitive conclusions have been drawn from randomized clinical trials of adjuvant chemotherapy for gastric cancer, because few studies have shown a significant positive impact on survival as compared with surgery alone. The negative results of most previous clinical studies do not necessarily mean that the adjuvant chemotherapy approach to treatment of gastric cancer does not work. Recent published reports of meta-analyses concerning adjuvant chemotherapy of gastric cancer revealed small but clear survival advantages for adjuvant therapy over surgery alone. The positive data from meta-analyses suggests that there are potential survival advantages of adjuvant chemotherapy, but this must be proven in the future by well-designed clinical trials that compare adjuvant chemotherapy with surgery alone, in which sufficient numbers of patients are enrolled and effective chemotherapeutic regimens with appropriate dose intensity are employed. Newly developed anticancer agents and/or newer therapeutic combinations or strategies (neoadjuvant chemotherapy, chemoradiotherapy, intraperitoneal chemotherapy) have the potential to benefit high-risk patients.
Synovial sarcoma is a mesenchymal tumor that has an epithelial character and two major histological subtypes, the biphasic type and the monophasic fibrous type. However, the mechanisms involved in its epithelial differentiation are unknown, and furthermore, the determinants for histological subtype in synovial sarcoma remain unclear. In this study, we immunohistochemically examined E-cadherin expression and screened for genetic alterations in the E-cadherin gene from exon 4 to exon 9 in 49 cases of synovial sarcoma. In addition, we also examined the mRNA expressions of E-cadherin and Snail, a direct repressor of E-cadherin gene expression, by reverse transcriptase-polymerase chain reaction in 20 samples of frozen material. Immunohistochemical E-cadherin membranous expression was observed in 12 cases (24.5%), and was predominant in biphasic tumors. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed 15 missense E-cadherin mutations in 12 cases (24.5%: monophasic, 11 of 42; biphasic, 1 of 6; poorly, 0 of 1) and 7 silent mutations (14.3%) in 7 cases. Ten of the 12 cases with E-cadherin missense mutations did not show E-cadherin membranous expression. Reverse transcriptase-polymerase chain reaction demonstrated E-cadherin and Snail mRNA expressions in 14 cases (70%) and in all cases, respectively. E-cadherin gene expression was inactivated by missense mutations in three of the eight cases (37.5%) of monophasic fibrous tumors that showed E-cadherin mRNA expressions. The E-cadherin gene was potentially inactivated in a significant number of synovial sarcomas. E-cadherin dysfunction because of its mutation in the central region of the molecule was associated with its decreased immunohistochemical expression and histological fibroblastic and spindle-shaped features of monophasic tumors. Thus, E-cadherin gene mutation may be one of the determinants of histological subtype in synovial sarcoma.
BACKGROUND: Roux-en-Y reconstruction with a jejunal pouch is a modified standard procedure in total gastrectomy for gastric cancer. The aim of the current study was to evaluate the usefulness of the reconstruction using a jejunal pouch in subsequent improvement of the nutritional condition of patients with gastric cancer after total gastrectomy. METHODS: Sixteen patients with gastric cancer treated by total gastrectomy and reconstruction with simple Roux-en-Y from January 1993 to December 1996 and 14 patients treated by total gastrectomy and reconstruction with Roux-en-Y and jejunal pouch from January 1997 to December 1998 were investigated in regard to postoperative heartburn, changes in the body weight, and prognostic nutritional index. RESULTS: Postoperative heartburn occurred in 1 patient (7.1%) among patients treated with Roux-en-Y and jejunal pouch and 3 (18.8%) among patients treated with simple Roux-en-Y. The body weight ratio at 1 year after operation in patients treated with Roux-en-Y and jejunal pouch (88.2% +/- 4.2%) was significantly higher than that in patients treated with simple Roux-en-Y (80.0% +/- 4.6%; P <0.01). The prognostic nutritional index ratios for patients treated with Roux-en-Y and jejunal pouch at 1 and 3 months after operation were 93.9% +/- 9.1% and 101.7% +/- 11.0%, respectively, and were significantly higher than that in patients treated with simple Roux-en-Y (86.2% +/- 8.8% and 88.1% +/- 8.2%, P <0.05 and P <0.01, respectively). CONCLUSIONS: Reconstruction using a jejunal pouch in total gastrectomy is useful for an early improvement of the nutritional condition of patients with gastric cancer.
BACKGROUND: Skin incision has been made directly in the breast for treatment of benign breast tumor in spite of the young age of the patient population. METHODS: Small incisions (12 mm, 5 mm, and 2 mm) were made in the extramammary line, and the benign tumors (diagnosed by imaging and aspiration needle cytology) were endoscopically extirpated. RESULTS: The mean age of 36 patients was 27.6 years, and the mean mass size was 3.6 cm (7 masses at maximum). The average operation time per mass was 2.6 hours in the first 18 operations and 1.4 hours in the latter 19 operations. Overall blood loss was 19 mL. Postoperative complications were seen in 2 patients: an extended subcutaneous emphysema due to excessive CO2 gas inflation and a mild burn, both of which were reversible. All patients were extremely satisfied with the cosmetic results of the procedure. CONCLUSIONS: Endoscopic removal by the extramammary approach is the best option for benign breast tumors considering the patient's age and the excellent cosmetic results.
BACKGROUND: Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. METHODS: Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. RESULTS: The alpha-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. CONCLUSIONS: Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.
BACKGROUND: Preoperative elevation of serum C-reactive protein (CRP) has been reported to be a prognostic indicator in gastric carcinoma and colorectal carcinoma. The aim of this study was to establish the significance of preoperative elevation of serum CRP as an indicator of prognosis in patients with esophageal carcinoma. METHODS: Two hundred sixty-two patients with esophageal carcinoma who had been treated by esophageal resection and reconstruction of digestive tracts were evaluated, excluding patients with neoplasms in other organs. Preoperative serum CRP was measured, and the relation between the elevation of serum CRP and the clinicopathological factors and prognosis of the patients was investigated. RESULTS: The mean size of the tumors and the proportions of lymph node metastasis and lymphatic invasion were significantly larger in patients with preoperative elevation of serum CRP than in patients without preoperative elevation of serum CRP (5.8 +/- 2.5 cm versus 4.8 +/- 2.5 cm, P <0.01, 59.5% versus 35.4%, P <0.001, and 35.7% versus 23.6%, P <0.05, respectively). 1-, 3-, and 5-year survival rates in patients with preoperative elevation of serum CRP (60.6%, 18.4%, and 11.5%, respectively) were significantly lower than those in patients without preoperative elevation of serum CRP (88.7%, 70.9%, and 68.4%, respectively; P <0.0001). Multivariate analysis demonstrated that the preoperative elevation of serum CRP was an independent prognostic factor in esophageal carcinoma (P <0.0001). CONCLUSIONS: The preoperative serum elevation of CRP can be a marker of the malignant potential of the tumor and an independent prognostic indicator in esophageal carcinoma.
BACKGROUND: The aim of the current study was to find out the clinicopathologic characteristics of younger patients with squamous cell carcinoma of the esophagus. METHODS: A total of 259 patients with esophageal squamous cell carcinoma who had been treated by esophagectomy and reconstruction within 10 years between January 1990 and December 1999 were studied. Clinicopathologic characteristics were compared between 27 patients younger than 50 years and 232 patients 50 years and older. RESULTS: A significant difference was observed with regard to the size of the tumor (6.3 +/- 3.8 cm in younger patients versus 5.0 +/- 2.4 cm in older patients; p = 0.017). The proportion of patients with TNM stage III or IV in younger patients (59.3%, 16 of 27) was significantly higher than that in older patients (38.3%, 89 of 232; p = 0.020). Nevertheless, no significant difference in the 1-, 3-, and 5-year survival rates was observed between younger patients (77.2%, 54.7%, and 54.7%, respectively) and older patients (81.9%, 54.2%, and 48.8%, respectively). CONCLUSIONS: Although the prognosis of younger patients with esophageal squamous cell carcinoma did not differ from that of older patients, esophageal squamous cell carcinoma in younger patients has more malignant potential and aggressive activity.
BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignant tumor with an extremely poor prognosis, but less attention has been directed to factors related to molecular carcinogenesis, including cell cycle proteins. We examined the expression and gene amplification of cyclin D1, the cell cycle regulating protein. Our objective was to evaluate correlations with clinicopathological factors in ICC. METHODS: Cyclin D1 overexpression and cellular proliferative activity (Ki-67 labeling index) were investigated immunohistochemically, and 20 cases were further investigated for cyclin D1 gene amplification, using differential PCR. We examined the correlation between the expression and gene amplification of cyclin D1 and clinicopathological factors, including overall survival in patients with ICC. RESULTS: Immunohistochemical analysis revealed an overexpression of cyclin D1 protein in 28 of 66 subjects with ICCs (42%). The cyclin D1 overexpression was associated with poor histological differentiation (P = 0.04), high cellular proliferative activity (P < 0.01), and a poor prognosis (P = 0.02) by univariate analysis, although it is not an independent prognostic factor by multivariate analysis. Cyclin D1 gene amplification was confirmed in five of the 20 patients. Of those five cases of ICC, all had poor histological differentiation, and four of the five ICCs (80%) showed evidence of cyclin D1 immunoreactivity. CONCLUSIONS: Overexpression and gene amplification of cyclin D1 are frequent and contribute to dedifferentiation and cellular proliferative activity of ICCs, and overexpression also indicates a poor prognosis for patients with ICC.
BACKGROUND/AIMS: To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. METHODS: To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. RESULTS: Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. CONCLUSIONS: The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.
BACKGROUND: The cell cycle progression is governed by a family of cyclin-dependent kinases, which are regulated by associated cyclins and by phosphorylation. p27, a cyclin-dependent kinase inhibitor, regulates the progression from G1 into the S phase by binding and inhibiting cyclin/cdks. Although p27 mutations in human tumors are extremely rare, a reduced expression of p27 might to lead to a progression of cancer cells. METHODS: We examined tissues that had been surgically excised from 161 unselected Japanese patients with non-small cell lung cancer, and investigated the p27 protein expression by immunohistochemistry. RESULTS: A reduced expression of the p27 protein was found in 63 cases (39.0%). Statistical correlation was found between the reduced p27 expression and advanced stage, although no correlation was found between the level of p27 expression and the gender, T factor, N factor or histological differentiation. The 5-year survival rate in the reduced group was 35.4%, which was statistically poorer than the 63.2% rate in the normal group (P=0.0016), in patients with complete resection. In a multivariate analysis, the level of p27 expression was found to be an independent prognostic indicator. CONCLUSIONS: We demonstrated the expression of p27 protein to be a biological prognostic indicator which can indicate the subsets of patients with either a good or poor prognosis, in patients who underwent surgical resection.
OBJECTIVES: We attempted to determine if the degree of angiogenesis can serve as a prognostic factor in the case of completely resected non-small cell lung cancer patients, with special reference to the center and the periphery of the tumor tissue. METHOD: For 255 Japanese patients who underwent completely resected non-small cell lung cancer (NSCLC), micro vessel density (MVD) was assessed by visual quantification of microvessels immunostained with anti-CD34 monoclonal antibody in 5 m section. Vascular endothelial growth factor (VEGF) was also immunostained on the same paraffin block specimen. RESULTS: MVD at the center (MVD-c) and that at the periphery (MVD-p) were frequently different in each individual although a weak positive correlation was observed (r=0.499, P<0.0001). One hundred and one patients with high MVD-p, but not the 107 patients with high MVD-c, showed a significantly higher proportion of advanced stage, larger tumor size and nodal metastasis as compared with MVD. The 5 year survival rate and median survival time for the high MVD-p group were significantly lower than that of low the MVD-p group (43.0%/31 months vs 48.6%/54 months, P=0.0256). As to the relationship among vascular endothelial growth factor (VEGF) and MVD, expression of VEGF was not associated with the degree of MVD. However, patients with high grade MVD-p showed an unfavorable prognosis in cases of high expression of VEGF. CONCLUSION: High MVD-p is associated with advancement of NSCLC, and it was particularly apparent in conjunction with high VEGF expression.
Vascular endothelial growth factor-C (VEGF-C) is a specific ligand which induces lymphangiogenesis. We examined the expression of VEGF-C protein to determine its role in the progression of breast cancer. Immunohistochemical analysis revealed that VEGF-C was overexpressed in 39 of 98 breast cancer specimens (39.8%) but not in adjacent normal mammary glands. The expression of VEGF-C showed a significant correlation with lymphatic vessel invasion (p = 0.0004). It is noteworthy that the 5-year disease free survival rate of the VEGF-C positive group was significantly poorer than that of negative group (p = 0.0356). We suggest that as expression of VEGF-C is not implicated in lymphatic spread, it may prove to be a promising marker to predict the recurrence of breast cancer.
Human esophageal carcinomas occur more frequently in males, suggesting that androgens may play a role in the regulation of gene expression associated with malignant transformation. We previously established an androgen-sensitive squamous cell carcinoma line, KSE-1, from a male patient with esophageal cancer; recently a novel isoform of human fibroblast growth factor 8 (FGF8f, isoform FGF8b) was identified and expressed following androgen stimulation of KSE-1 cells. The predicted amino acid sequence of FGF8f contained an additional 29 amino acids when compared to FGF8b. Flutamide, an androgen antagonist, inhibited both FGF8b and FGF8f transcription in a dose-dependent manner. Tissue analysis from tumors revealed FGF8b expression in 24 of 41 male, but in 0 of 9 female esophageal carcinomas (58.5%), and none in adjacent normal esophageal mucosa. In addition, FGF8f was detected in 9 of 24 FGF8b-positive tumors (37.5%), and this observation was significantly associated with a poor prognosis (P < 0.001). Our observations suggest that androgenic exposure will induce FGF isoforms in tumor cells, and expression of these growth factors is associated with the prevalence and prognosis of esophageal carcinoma in males.