Effect of dietary molybdenum on esophageal carcinogenesis in rats induced by N-methyl-N-benzylnitrosamine.

The influence of dietary molybdenum on esophageal carcinogenesis induced by N-methyl-N-benzylnitrosamine (2.5 mg per kg of body weight once a week for 20 wk s.c.) was studied in male F344 rats. The tumor incidence and tumor development in the esophagus were significantly lower in the rats in the high-molybdenum (2 ppm) diet group than in the rats in the low-molybdenum (0.032 ppm) diet group; i.e., 44.4% (0.6 +/- 0.8) and 73.2% (2.2 +/- 2.0), respectively. The molybdenum levels in the esophagus-forestomach, liver, and serum were significantly higher in the high-molybdenum diet group than in the low-molybdenum diet group. Xanthine oxidase activity in the esophagus and forestomach in the high-molybdenum diet group was significantly higher than that in the low-molybdenum diet group, whereas liver and serum xanthine oxidase activities were not significantly different between these two groups. These results suggest that xanthine oxidase in the esophagus plays a significant role in the inhibitory effect of molybdenum on esophageal carcinogenesis.

Stromal CEA immunoreactivity is correlated with lymphatic invasion of human esophageal carcinoma.

Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e. modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human esophageal carcinomas. In this study, we examined CEA expression in human esophageal squamous cell carcinoma and its clinicopathological significance. CEA immunoreactivity was frequently detected in the cancer cells (cytoplasmic type; 81.1%, 43/53) as well as in the cancer stroma (stromal type; 32.1%, 17/53), regardless of the depth of tumor invasion. Lymphatic invasion of cancer cells was frequently found in the stromal CEA-positive esophageal cancer (44.4%, 16/36), compared to stromal CEA-negative cancer (5.9%, 1/17) (p<0.05). These observations suggested that stromal CEA expression plays important roles in lymphatic invasion of human esophageal squamous cell carcinoma.

Frequent expression of inducible nitric oxide synthase in esophageal squamous cell carcinomas.

Nitric oxide (NO) plays important biological roles in cardiovascular, nervous and immune systems, and is synthesized by nitric oxide synthase (NOS). Intracellular NO is known to cause DNA damage as a mutagen. We examined the expression of cytokine-inducible NOS (iNOS) in human esophageal squamous cell carcinomas. Weak iNOS immunoreactivity was seen in the basal and parabasal layers of non-neoplastic esophageal stratified squamous epithelium. iNOS expression was detected in 50 (87.7%) of the 57 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, histological differentiation and lymph node status. Early-stage cancers, i.e. mucosal squamous cell carcinomas, also showed significant iNOS expression. We speculate that increased iNOS expression is associated with the carcinogenesis of human esophageal cancer.

Frequent expression of sialyl Le(a) in human esophageal squamous cell carcinoma.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Le(a) is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human esophageal carcinomas. In this study, we examined sialyl Le(a) expression and its histopathological localization in human esophageal squamous cell carcinoma. Sialyl Le(a) immunoreactivity was detected in 28 (51.9%) of the 54 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, vascular invasion or lymph nodal status. In 13 cases (29.5%), significant sialyl Le(a) expression was detected not only in the intramucosal carcinoma components, but also in the invasive carcinoma components. These observation suggested that sialyl Le(a) expression is associated with early-stage cancer progression.

Delayed hyperacute xenograft rejection in porcine to canine fetal liver transplantation.

Fetal tissues are generally considered to express weaker antigenic cell-surface molecules than adult tissues. We have reported that transplantation of porcine fetal liver tissue (fragments) is useful for acute and chronic hepatic failure in rats. We further investigated, in the present study, whether transplantation of a porcine fetal liver has the advantage of delayed hyperacute xenograft rejection (HAR) in comparison with that of an adult liver. Porcine fetal liver heterotopically transplanted into dogs was compared. Haematoxylin-eosin (HE) and immunohistochemical studies using IgM, C3, IgG antibodies were performed in serial biopsies of the liver grafts. Lectin binding to target antigen epitopes on pig and dog tissues was studied by flow cytometry. Carbohydrate expression on the liver was also studied by immunohistochemistry. The macroscopic and HE section findings indicate that HAR started 15 min postgraft in fetal and adult liver grafts. Thereafter, vascular changes and parenchymal damage progressed more rapidly in the adult grafts. The final HAR time in adult liver transplantation was determined to be 60 min, while it was determined to be 180 min in fetal liver transplantation. IgM, C3 and IgG were deposited more strongly in the adult grafts than in the fetal grafts up until 60 min after xenografting. Phaseolus vulgaris erythroagglutinin lectin competitively blocked dog sera binding to porcine PBLs. The fetal liver expressed oligosaccharide at a significantly lower level than the adult liver. We conclude that porcine fetal liver xenografts had a significantly delayed HAR.

Accumulation of p53 in esophageal squamous cell carcinoma.

p53 is one of the most important tumor suppressor genes. Mutation of the p53 gene can be detected immunohistochemically as over-expression of its protein in the nucleus. The p53 gene product is known to regulate cell growth and proliferation. Genetic alterations related to the carcinogenesis or progression of esophageal cancer are poorly understood. We examined accumulation of p53 protein in esophageal squamous cell carcinomas including early-stage cancers, and its clinicopathological significance. p53 immunoreactivity in the cancer tissues was found in 61 (79.2%) of 77 esophageal squamous cell carcinomas. Over-expression of p53 protein (diffusely and focally positive staining) was seen in 70.1% (54/77). p53 over-expression was detected not only in the cases of in situ or intramucosal carcinomas, but also in invasive carcinomas. No significant correlations were found between p53 over-expression and clinicopathological features such as depth of tumor invasion, lymph node metastasis or venous/lymphatic invasion. These results suggested that p53 mutations may be closely associated with the early-stage of pre-invasive esophageal carcinoma, and p53 gene mutations may play an important role in the carcinogenesis of human esophageal cancer.

Clinicopathological studies of esophageal carcinoma in achalasia: analyses of carcinogenesis using histological and immunohistochemical procedures.

Achalasia of the esophagus is a benign disease caused by dyskinesia of the lower esophagus and cardia and is presumed to be a premalignant lesion leading to an increased risk of squamous cell carcinoma. We analyzed six surgically or endoscopically resected carcinomas among 54 cases of esophageal achalasia using histological and immunohistochemical procedures. The mean interval between the diagnosis of achalasia and carcinoma was 21.5 years. Four of the six cases were superficial early-stage cancers whilst the other two were advanced cancers invading the adventitia. Histological mapping of the resected esophageal specimens demonstrated marked hyperplastic changes of stratified squamous epithelium and multiple foci of dysplastic changes. The squamous cell carcinomas showed well-differentiated type with low-grade atypia, closely associated with dysplastic foci. Immunohistochemical staining for p53, p21, p16 and epidermal growth factor receptor suggested that the dysplastic epithelium was a borderline lesion between hyperplasia and in situ carcinoma. Our observations suggested that esophageal food stasis induces chronic hyperplastic esophagitis and eventually malignant transformation of esophageal epithelial cells, associated with dysplasia-carcinoma sequence.

Immunohistochemical MUC1 (DF3 antigen) expression of human esophageal squamous cell carcinoma.

MUC1 (DF3 antigen) is a member of a family of high molecular weight glycoproteins. Recent studies have demonstrated that MUC1 is expressed in tumors of various human organs and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. However, expression patterns of MUC1 have not yet been established in human esophageal carcinomas. In this study, we examined MUC1 expression and its histopathological localization in human esophageal squamous cell carcinoma. MUC1 immunoreactivity was found in 17 (32.1%) out of 53 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, vascular invasion or lymph node status. MUC1 expression was detected in the intramucosal part in 28.3% (15 out of 53) and in the invasive part in 32.6% (14 out of 43) of the esophageal carcinomas (no significant difference). These observations suggested that expression of MUC1 is an early event in cancer progression, but that it is not significantly associated with metastasis of human esophageal carcinomas.

Stromal thrombospondin-1 expression is correlated with progression of esophageal squamous cell carcinomas.

Thrombospondin-1 (TSP1) is an extracellular matrix glycoproteins that affecting cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we clarified TSP1 immunoreactivity in human esophageal squamous cell carcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 70.6% (12/17) of the T3 esophageal cancers were TSP1-positive, while only 26.9% (7/26) of the Tis and T1 cancers showed TSP1 expression. Lymph node metastasis and venous involvement was frequently found in the TSP1-positive cases (71.4% and 80.0%, respectively) of esophageal squamous cell carcinoma (p < 0.001). This observation suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human esophageal squamous cell carcinomas, and that stromal TSP1 immunoreactivity is a good predictor of venous involvement and lymph node metastasis.

Branched-chain amino acid-supplemented nutritional support after gastrectomy for gastric cancer with special reference to plasma amino acid profiles.

Preoperative plasma aminograms constructed for 63 patients expected to undergo gastrectomy for gastric cancer at different stages showed markedly lower concentrations of many plasma amino acids in the Stage IV and recurrent cases. The amino acid levels were inversely proportional to tumor size. On the other hand, preoperative arteriovenous differences in free amino acid levels were positive in Stage I cancer but negative in Stage IV cancer, indicating that intake of amino acids by the skeletal muscles exceeded the outflow in Stage I, whereas there was a net loss of amino acids from the skeletal muscles in advanced cancer. The amount of amino acids actually lost from the skeletal muscles after muscular loading in Stage I cancer also surpassed that in Stage IV cancer. Administration of TPN solution supplemented with 31% branched-chain amino acids (BCAA) might favorably influence muscle protein metabolism in gastric cancer patients by inhibiting protein degradation and promoting synthesis, as treatment was more effective than 21% BCAA-enriched TPN.

Comparison between thoracoabdominal and abdominal approaches in occurrence of pleural effusion after liver cancer surgery.

BACKGROUND/AIMS: Pleural effusion is a complication occasionally encountered in hepatic surgery. The production of pleural effusion was compared between thoracoabdominal and abdominal approach for hepatic surgery of hepatocellular carcinoma. METHODOLOGY: All the 98 patients undergoing liver resection for hepatocellular carcinoma at the National Cancer Center Hospital from May 1992 to March 1994 were included into the study, of those 70 were by the thoracoabdominal and 28 by the standard abdominal approach. Comparisons were made in regard to the rate of pleural effusion, the rate of postoperative thoracentesis, the number of postoperative thoracentesis procedures per patient, the total volume of pleural effusion obtained by thoracentesis per patient, and the duration of pleural effusion. RESULTS: Forty-three percent of patients treated with the abdominal approach in contrast to 73% of patients treated with the thoracoabdominal approach developed pleural effusion (p < 0.01). Seven percent of the patients treated with the abdominal approach in contrast to 17% of the patients treated by the thoraco-abdominal approach required thoracentesis. The number of thoracentesis required for the abdominal approach was 1, for the thoracoabdominal approach was 3 (p < 0.02). The bile leakage rate was 17% for thoracoabdominal versus 33% for abdominal approach. CONCLUSIONS: Due to frequent pleural effusion, the thoracoabdominal approach should not be used for every liver operation. However, when treatment to the neck of the right hepatic vein is necessary, the thoracoabdominal approach might be recommended because of the easy access to the operating field and the reduced rate of bile leakage.

Descending necrotizing mediastinitis due to odontogenic infections.

OBJECTIVE: Acute purulent mediastinitis caused by oropharyngeal infection is termed descending necrotizing mediastinitis. Such infections usually have a fulminate course, leading to sepsis and frequently to death. The purpose of this study is to show the importance of early diagnosis, aggressive surgical intervention, and optimal antibiotics chemotherapy in controlling this fatal infectious disease. STUDY DESIGN: Two patients with descending necrotizing mediastinitis due to odontogenic infection who were treated at our institution are described. RESULTS: Both patients survived. CONCLUSIONS: From the patients, 23 different aerobic and anaerobic bacteria were isolated. All of the isolates were susceptible to carbapenem. Early evaluation by means of cervicothoracic computed tomography scanning was extremely useful for diagnosis and surgical planning. Knowledge of anatomic pathways from the mouth to the mediastinum is essential. We believe that tracheostomy is not always necessary. In both of the cases presented, mediastinal drainage was completed through use of a transcervical approach. However, a more aggressive drainage including tracheostomy might be necessary when the infection extends below the carina.

Preliminary study for sentinel lymph node identification with Tc-99m tin colloid in patients with esophageal or gastric cancer.

The purpose of this study is to determine whether a lymph node identified with high radioisotope (RI) activity is a sentinel node. We studied 26 patients with either esophageal or gastric cancer whose preoperative imaging studies showed no lymph node metastasis. Before surgery, Tc-99m tin colloid was injected via endoscopy into the submucosa. In lymph nodes dissected at surgery, RI activity was measured by a scintillation counter, and metastatic status was examined by hematoxylin-eosin staining. The number of dissected nodes was 45 +/- 15 (mean +/- SD) per patient, and the number of nodes with high RI activity was 4 +/- 1. Nodal metastasis occurred in 11 of 26 patients. In 9 of these 11 patients, metastatic foci were found in one or more nodes with high RI activity. In one of the 2 remaining patients, endoscopic clipping was applied just above the injection sites, and in the other patient, the tumor invasion was beyond the muscle layer. For further analysis, the case with clipping was excluded, and only those in which the tumor invasion was confined within the muscle layer were evaluated. Six of 18 patients in this analysis showed nodal metastasis. Each of the 6 patients had at least one node that showed high RI activity and that was positive for metastasis. We conclude that when tumor invasion remains within the muscle layer, lymph nodes with high RI activity can be regarded as sentinel nodes.

Endoscopic screening for esophageal cancer in 788 patients with head and neck cancers.

Esophageal cancer has a poor prognosis because it is difficult to detect in its early stages and, even if an operation is possible, the postoperative quality of life is much impaired. An early diagnosis can lead to a good prognosis and enables treatment by endoscopic mucosal resection (EEMR), contributing to a postoperative good quality of life. As head and neck cancers are known to have a high risk of concomitant esophageal cancer, endoscopic screening with iodine staining was performed on 788 patients with head and neck cancers. Among them, 93 cases of esophageal cancers (11.8%) and 23 cases of gastric cancers (2.9%) were detected. Seventy-two cases (77.4%) of the 93 esophageal cancers were superficial cancers limited to the submucosal layer. Twenty cases, treated by EEMR, had a good postoperative course without local recurrence. We suggest that endoscopic screening for esophageal cancer should be performed on all patients with head and neck cancers, because it allows early detection and a good prognosis, and the treatment can be completed by endoscopic maneuver.

Imaging features contributing to the diagnosis of ameloblastomas and keratocystic odontogenic tumours: logistic regression analysis.

OBJECTIVE: The aim of this study was to clarify the characteristic imaging features that can be used to differentiate ameloblastomas from keratocystic odontogenic tumours and to examine the significant imaging features contributing to a correct diagnosis. METHODS: 60 observers (39 specialists in oral and maxillofacial radiology and 21 non-specialists) examined CT and/or panoramic images of 10 ameloblastomas and 10 keratocystic odontogenic tumours shown on a webpage and made diagnoses. Their correct answer ratios were then calculated. The imaging features of the tumours were evaluated and expressed as binary numbers or quantitative values. The imaging features that contributed to a correct diagnosis were elucidated using logistic regression analysis. RESULTS: The mean correct answer ratio was 61.3% ± 17.2% for the diagnosis of ameloblastomas and keratocystic odontogenic tumours. CT images produced higher correct answer ratios for diagnosis of keratocystic odontogenic tumours by specialists. The significantly different imaging features between ameloblastomas and keratocystic odontogenic tumours were the degree of bone expansion and the presence of high-density areas. The significant imaging features contributing to a correct imaging diagnosis were the number of locules, the presence of high-density areas and the inclusion of impacted teeth. CONCLUSION: The presence of high-density areas is the most useful feature in the differential diagnosis of ameloblastomas and keratocystic odontogenic tumours based on comparison of the imaging features of both tumours and examination of the diagnostic contributions of these features.

Endoscopic mucosal resection for early gastric cancer.

Progress in the detection of early gastric cancer has made endoscopic mucosal resection (EMR) possible for the treatment of gastric cancer instead of only conventional surgical resection. The most commonly employed modalities include strip biopsy, double snare polypectomy, and resection with combined use of highly concentrated saline and epinephrine, and resection using a cap. The indications should be strictly limited to the differentiated IIa type (the slightly elevated type) that is smaller than 2 cm, or the differentiated IIc type (slightly depressed type) without ulcer formation and smaller than 1 cm. Both of these entities are thought to have a negligible risk of lymph node metastasis. Prognosis after this treatment is comparable that of surgical resection for early gastric cancer in completely resected cases. EMR also permits local resection in elderly patients with various complications who would be at risk for conventional surgical operations. EMR should be encouraged for treatment of gastric cancer if the indications are strictly chosen.

Inhibitory effect of selenium on hamster pancreatic cancer induction by N'-nitrosobis(2-oxopropyl)amine.

The effect of selenium intake on the development of pancreatic cancer was investigated in female Syrian golden hamsters. Four-week-old hamsters were divided into 2 groups according to the selenium level in their drinking water and were fed a purified diet containing less than 0.05 ppm selenium. Starting 4 weeks later, groups received 10 s.c. injections at weekly intervals of N'-nitrosobis(2-oxopropyl)amine (BOP) dissolved in saline, while controls received saline alone. When the animals were killed 18 weeks after the last injection, palpable tumors were less frequent in the high-selenium group than in animals receiving low-selenium supplement, the numbers of histologically diagnosed cancerous lesions also being significantly reduced by high selenium intake. The selenium level and glutathione peroxidase activity in serum and pancreas were significantly greater in the high-selenium group. Moreover, selenium levels and glutathione peroxidase activity were both significantly higher in tumor-bearing tissue. The results suggest that glutathione peroxidase is involved as an intermediate factor in prevention of carcinogenesis by selenium.