Comparative study of treatment for distal radius fractures with two different palmar locking plates.

Few randomized trials have shown how the placement of a palmar locking plate affects outcomes. The purpose of this study was to compare clinical and radiological outcomes of fixation using locking plates with different concepts for placement relative to the watershed line in a prospective randomized trial. Sixty-four patients with a displaced distal radius fracture were divided into two groups according to the plates used for fixation: distal-type (AcuLoc(TM), Group A) and proximal-type (VariAx(TM), Group V). Wrist function including the range of motion and grip strength was compared at 1, 2, 3 and 6 months postoperatively. Loss of reduction was assessed radiologically. Both groups demonstrated overall satisfactory function at 6 months with no significant difference found between the groups. Minimal loss of reduction was demonstrated in both groups. Internal fixation using the palmar locking plates with two different placements provided satisfactory outcomes at 6-month follow-up, but our results indicate that plates placed distal to the watershed line may delay recovery of wrist motion.

MAGE-A protein and MAGE-A10 gene expressions in liver metastasis in patients with stomach cancer.

Tumour samples from 71 patients with stomach cancer, 41 patients with liver metastasis (group A) and 15 patients each in stages II-IV (group B) and stage I (group C) without liver metastasis were analysed. MAGE-A protein expression was evaluated by immunohistochemistry using a 6C1 monoclonal antibody and MAGE-A10 mRNA expression was detected by highly sensitive in situ hybridisation using a cRNA probe. Expressions of MAGE-A protein and MAGE-A10 mRNA in group A were detected in 65.9 and 80.5%, respectively. Both protein and gene showed significantly higher expression in group A than those in groups B (6.7, 26.7%) and C (0, 0%) (P=0.0003, P=<0.0001, respectively). MAGE-A10 mRNA expression in liver metastasis was found in eight (88.9%) out of nine patients. The concordant rate between MAGE-A family protein expression and MAGE-A10 mRNA expression in the primary sites was 81.7% (P<0.0001). MAGE-A10 gene expression was associated with reduced survival duration. The results of this study suggest that MAGE-A10 is a possible target in active immunotherapy for advanced stomach cancer.

Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endocytoscope: a pilot trial.

BACKGROUND AND STUDY AIMS: A newly designed magnifying endoscope featuring an endocytoscopy function provided by ultrahigh magnification was evaluated in a pilot study in patients with various types of benign and malignant pathology in the esophagus. PATIENTS AND METHODS: Seventy-five consecutive patients were included in the study from 15 March to 21 December 2005. Twenty-nine patients with specific esophageal lesions that had been detected by regular or narrow-band imaging, or both, were further evaluated using endocytoscopy, followed by tissue biopsy or resection. During the endocytoscopic examinations, the esophageal mucosa was stained with 0.5 % methylene blue. The endocytoscopic findings were graded from 1 to 5 in an endocytoscopic atypia (ECA) classification. The final histopathological diagnoses based on biopsies or resected specimens were as follows: category 1 in the Vienna classification, n = 4; category 2, n = 6; category 3, n = 1; category 4, n = 10; and category 5, n = 7. The endocytoscopic diagnoses were compared with the histopathological diagnoses. RESULTS: Clear endocytoscopic images were obtained in all cases. In definitely malignant lesions, the cell nuclei had an enlarged and irregularly arranged appearance (grade ECA 5). The positive predictive value for malignancy (grades ECA 4 and 5) was 94 %; the false-negative rate was 16.7 %, and the false-positive rate was 6.3 %. The overall accuracy of endocytoscopy for differentiating between nonmalignant tissue (categories 1 - 3 in the Vienna classification) and malignant tissue (categories 4 and 5) was 82 %. CONCLUSIONS: These preliminary results suggest that incorporating endocytoscopy facilities into a standard endoscope may be helpful in characterizing tissue in a variety of esophageal lesions. The potential clinical impact of this method in relation to other gastrointestinal organs requires further study.

Differential expression of TCEAL1 in esophageal cancers by custom cDNA microarray analysis.

To find new genes involved in esophageal squamous cell carcinogenesis, we constructed custom cDNA arrays and used the arrays to compare gene expression profiles of 12 matched normal and malignant esophageal samples including seven superficial cancer tissues. The arrays represented nearly 4000 genes, including 1728 that were specifically selected based on pilot studies to find genes that were differentially expressed in esophageal cancers. Expression values for all genes were normalized for each sample and were compared in normal versus tumor tissues. There was a marked decrease in the levels of the transcriptional elongation factor A gene in all 12 of the squamous cell cancer samples compared to matched normal samples. Because the transcription elongation factor A gene has not been previously reported to be involved in cancer development, our results suggest that further investigation of its role in esophageal carcinogenesis is warranted.

Response to preoperative chemotherapy affects prognosis in esophageal cancer.

The effect of preoperative chemotherapy on prognosis is still controversial. We have investigated the relationship between responses to preoperative chemotherapy and prognosis after curative operations in patients with esophageal squamous cell carcinoma. Thirty-nine patients received preoperative chemotherapy with continuous infusion of 500 mg/m2 of 5-fluorouracil (5-FU) and intravenous injection of 20 mg/m2 of leucovorin every 12 hours for 5 days. On the 5th day alone, 70 mg/m2 of cisplatin was also infused. The effect was evaluated approximately 14 days after the end of one course of chemotherapy. The rates of responders and non-responders were 64.1% and 35.9%, respectively. After an interval of 21-28 days, transthoracic esophagectomy was performed. Significant histological effect by chemotherapy was found in responders compared to non-responders (P < 0.05). Responders had a significantly better prognosis than non-responders by Log-rank test (P < 0.01). This suggests that preoperative chemotherapy may contribute to better prognosis when the tumor is sensitive to chemotherapy.

Endoscopic mucosal resection scissors for the treatment of early gastric cancer.

Endoscopic mucosal resection (EMR) is currently a common treatment for superficial gastrointestinal tumors. We have developed new EMR scissors for superficial lesions in the esophagus and stomach. These scissors have stainless steel blades with an electrocoagulation device for hemostasis. We report a case in which superficial gastric cancer was treated by means of the EMR scissors. The lesion was removed using the scissors and no major complication was encountered. EMR scissors can be used for endoscopic resection of superficial lesions of the esophagus and stomach.

Effects of preoperative chemotherapy on metastatic lymph nodes in esophageal squamous cell carcinoma.

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.

Effectiveness of preoperative chemotherapy using carboplatin (CBDCA) and surgery against an esophageal small cell carcinoma.

A 63-year-old man presented to our hospital with persistent dysphagia. Radiologic and endoscopic examination disclosed a 2.0-cm exophytic tumor in the middle third of the esophagus. An endscopically obtained biopsy specimen was found to represent undifferentiated small cell carcinoma. Computed tomography of the chest, abdomen, and cervical region was performed, as were gallium and bone scintigraphy. Metastasis to an adjacent lymph node was detected, without metastasis to distant organs. After neoadjuvant chemotherapy with carboplatin (CBDCA) (400 mg/m2) and etoposide (VP-16) (100 mg/m2), endoscopy and barium-swallow esophagography showed regression. Thoracic esophagectomy then was performed with mediastinal, abdominal and cervical lymph node dissection. The resected tumor was polypoid, measuring 0.5 x 0.5 cm. The lesion consisted mainly of small anaplastic cells, but included a small focus of squamous cell carcinoma. The patient has survived for more than 7 months with no further treatment and no evidence of recurrent disease.

Cyclin D1 overexpression as a prognostic factor in patients with esophageal carcinoma.

BACKGROUND AND OBJECTIVES: Cyclin D1 is known to play important roles in the G1/S check-point of the cell cycle. We investigated the correlation between cyclin D1 overexpression and clinical characteristics to clarify its prognostic significance in patients with esophageal cancer. METHODS: From 1991 to 1998, cyclin D1 was investigated in esophageal cancers from 86 patients who underwent esophagectomy. Overexpression of cyclin D1 was demonstrated using an immunohistochemical method. RESULTS: Overexpression of cyclin D1 was found in 23 (26.7%) of 86 cases. Overexpression of cyclin D1 correlated with lymph node metastasis (P = 0.0083) and lymphatic vessel invasion (P = 0.018). Cyclin D1 overexpression may indicate resistance to chemotherapy. The patients with cyclin D1 overexpression had a significantly lower survival rate than those without overexpression (P = 0.013). The multivariate analysis revealed cyclin D1 overexpression to be an important prognostic factor in patients with esophageal cancer. CONCLUSIONS: Immunohistochemical examination of cyclin D1 expression may provide important prognostic information in univariate and multivariate analysis and may be necessary for determining therapeutic strategies for esophageal cancer.

Liver abscesses associated with stromal tumour of the stomach in a young woman.

A 23-year-old Japanese woman was admitted to hospital because of pyrexia and anaemia. She was found to have liver abscesses and a gastric submucosal mass by computed tomography and ultrasonography. Gastroscopy and a barium swallow revealed a round submucosal mass with a giant ulceration in the body of the stomach. The liver abscesses were successfully treated by percutaneous transhepatic drainage and intravenous administration of antibiotics. Cultures of the fluid from a liver abscess and gastric juice yielded alpha-haemolytic streptococci. Three weeks after the drainage, partial gastrectomy was performed. The tumour was diagnosed as a stromal tumour of the stomach (leiomyosarcoma) in the final histological report. The patient was discharged on postoperative day 17 without receiving adjuvant radio-chemotherapy. There have been no signs of recurrence two years after surgery. This is a rare case of a liver abscess associated with a stromal tumour of the stomach in a young patient. The bacteriological examinations suggested a possible association between these diseases.

Wide-spread distribution of sentinel lymph nodes in esophageal cancer.

Sentinel lymph nodes are the first draining nodes that contain tumor cells. Identification of sentinel nodes may help to determine the suitable extent of lymphadenectoy. To assess the location of sentinel lymph nodes, a series of 41 patients with single and two metastatic lymph nodes who underwent esophagectomy and 3-field lymphadenectomy between 1991 and 1999 were investigated retrospectively. Only 29 (47.5%) of 61 metastatic nodes showed correspondence between the tumor site and the regional metastatic lymph nodes by routine histologic examination. In the patients with tumors in the upper and middle thoracic esophagus, metastatic lymph nodes were distributed in the cervix, mediastinum and abdomen. Although sentinel nodes were limited to the regional and adjusting compartments in 82%, nodes were found beyond the adjusting compartments in 18%. The sentinel nodes were broadly distributed depending on the location of the tumor in esophageal cancer.

Primary malignant melanoma of the esophagus treated by esophagectomy and systemic chemotherapy.

We describe herein a case of asymptomatic primary malignant melanoma of the esophagus. A 65-year-old man presented with a 4-cm filling defect in the middle third of the esophagus on a routine barium swallow. Subtotal esophagectomy accompanied by lymph node dissection was performed through a right thoracotomy. Postoperatively, the patient received five cycles of systemic chemotherapy with dacarbazine (DTIC), nimustine hydrochloride (ACNU), and vincristine (VCR) (DAV therapy), but ultimately died of generalized metastatic disease 15 months after surgery. Malignant melanoma of the esophagus has an extremely poor prognosis despite various therapeutic efforts.

Inhibited serum phospholipase A2 activity in hyperbilirubinemia.

BACKGROUND/AIMS: Phospholipase A2 activity is reported to be related to the physiology of various disorders, and the activity is modified by deoxycholic acid. METHODOLOGY: Serum phospholipase A2 activity was measured by counting the radioactivity of 14C-palmitic acid released from L-3-phosphatidylcholine (1-palmitoyl-2-14C-palmitoyl) in 40 patients with hyperbilirubinemia due to malignant neoplasms and benign cholestasis. Phospholipase A2 activity in serum from healthy subjects was also measured after incubation with 5-30 mg of bilirubin per dL or 0.1-5 mM of cholic acid for 60 min at 37 degrees C. RESULTS: Serum phospholipase A2 activity was significantly lower in patients with hyperbilirubinemia. There were negative correlations between serum phospholipase A2 activity and concentration of total bilirubin (r = 0.668; P < 0.0001) or total bile acids (r = 0.423; P < 0.05) in patients with hyperbilirubinemia. In 12 patients who underwent percutaneous transhepatic biliary drainage, the low serum phospholipase A2 activity was reversed while bilirubin concentrations decreased. Incubation of sera from healthy subjects with more than 3 mM cholic acid significantly reduced phospholipase A2 activity (P < 0.01), whereas incubation with bilirubin had no effect. CONCLUSIONS: Inhibition of serum phospholipase A2 activity in patients with hyperbilirubinemia may be caused by increased serum cholic acid concentration.

Telomere shortening with aging in human liver.

Progressive telomere shortening with aging was studied in the normal liver tissue of 94 human subjects aged between 0 and 101 years old to determine the rate of telomere loss in 1 year. Telomere length demonstrated accelerated shortening with reduction of 55 base pairs (bp) per year. The mean telomere length in five neonates was 12.9 +/- 2.6 kilobase pairs (kbp), and that in one centenarian was 8.3 kbp. Mean telomere lengths by age group were 13.2 +/- 2.0 kbp (< or = 8 years; 10 subjects), 7.8 +/- 1.9 kbp (40-79 years; 29 subjects), and 7.5 +/- 2.0 kbp (> or = 80 years; 53 subjects), with reduction thus appearing to show slowing on the attainment of middle age. The difference of mean telomere lengths for two groups with or without advanced malignancies of other than liver origin was not significant in the older two groups. Despite the slow turnover of liver tissue, the overall reduction rate of telomere length decrease in 1 year was almost the same as that of digestive tract mucosa, with its very rapid renewal.

Correlation of telomere lengths in normal and cancers tissue in the large bowel.

The hypothesis that telomeres in colorectal cancer cells exhibit age-related shortening, as in normal cells of the colorectal epithelium, was tested with samples of non-cancerous mucosa and cancer tissue from 124 patients (aged 29-97 years). Shortening with aging could be demonstrated for both normal and cancer tissues; regression analysis showed rates for length reduction of 44 and 50 base pair/year, respectively. Straight, essentially parallel, lines were obtained for the two cases, normal tissue values being about 2 kilobase pairs (kbp) higher, with a significant correlation between data at the individual patient level.

Detection of circulating anti-p53 antibodies in esophageal cancer patients.

It has been reported that circulating anti-p53 antibodies (p53-Ab) in the serum are detected in some cancers. To investigate the usefulness of detecting p53-Ab, we measured the circulating p53-Ab in comparison with squamous cell carcinoma antigen (SCC-Ag) in patients with esophageal carcinoma. Serum specimens from 46 esophageal cancer patients (42 squamous cell carcinomas, 3 mucoepidermoid carcinomas and 1 basaloid squamous carcinoma) and 13 healthy subjects were studied. Serum p53-Ab was measured by an enzyme-linked immunosorbent assay. Surgically resected specimens from 43 patients were immunohistochemically stained for p53. Serum SCC-Ag was measured by a radioimmunoassay. The results were analyzed with the clinical data and outcome. Serum p53-Ab was detected in 13 (28%) of the 46 patients, but not in any of the healthy subjects. The positive rate was 0% (0/6) in stage I, 60% (3/5) in stage IIA, 30% (3/10) in stage IIB, 29% (7/24) in stage III and 0% (0/1) in stage IV. There was no difference in the outcome between the p53-Ab-positive and p53-Ab-negative patients. Immunohistochemically, 30 (70%) of the 43 specimens stained positively for p53. Serum p53-Ab was detected in 43% (13/30) of the patients with tumors which stained positively for p53. There was a close correlation between positivity for p53 immunostaining and positivity for p53-Ab (p<0.01). An elevated level of SCC-Ag was found in only 13%of the patients, and most patients positive for SCC-Ag already had advanced disease with lymph node metastasis and invasion to the adventitia. In conclusion, serum p53-Ab was detected in Japanese esophageal cancer patients at a frequency similar to that reported in Western countries. Serum p53-Ab may be a potentially useful molecular marker for detection and screening of esophageal cancer. Further studies of a large population may be required to elucidate the true diagnostic usefulness of measuring the serum p53-Ab.

Multiple primary malignant neoplasms in patients with esophageal cancer.

This study aims to elucidate the incidence and the therapeutic and prognostic implications of co-existent non-esophageal primary malignant neoplasms in patients with esophageal cancer. Between 1974 and 1997, 33 patients with esophageal cancer treated at the Nippon Medical School Hospital were documented as having multiple primary malignant neoplasms (MPN). The therapeutic strategies and post-therapeutic survival of these patients were retrospectively investigated. Among 291 patients with esophageal cancer, 33 patients (11.3%) were also found to have non-esophageal primary malignant neoplasms. Twenty patients (60.6%) had synchronous MPN and 13 (39.4%) had metachronous MPN. Among the MPN, apart from esophageal cancer, gastric (32.6%) and head and neck cancer (32.6%) were the most common. The incidence of esophageal cancer occuring in association with cancers of the head and neck or gastric cancer was high. Frequent examination in these cancer patients, using fiberoptic esophagogastric endoscopy for example, may be helpful in the early diagnosis of esophageal cancer.

Detection of T cell apoptosis after major operations.

OBJECTIVE: To detect T cell apoptosis in reduced peripheral lymphocyte counts in patients having major operations. DESIGN: Prospective study. SETTING: University hospital, Japan. SUBJECTS: 11 patients having oesophagectomy and 5 having laparoscopic cholecystectomy. INTERVENTIONS: To investigate T cell apoptosis we detected DNA fragmentation using electrophoresis, and T-cell receptor-gamma (TCR-gamma) gene amplification using polymerase chain reaction (PCR) in serum. MAIN OUTCOME MEASURES: Peripheral lymphocyte count and DNA extracted from the serum preoperatively and on postoperative days 1, 3, 5, and 7. RESULTS: The lymphocyte count decreased significantly until day 5 and then increased in the patients who had had oesophagectomy. DNA fragmentation and PCR products for the TCRgamma variable region gene were found in the serum DNA of 10 patients until day 5. No DNA fragmentation or PCR products were found in the serum of patients who had had laparoscopic cholecystectomy. CONCLUSION: These results suggest that transient T cell apoptosis occurs after major operations.

[Effects of intravenous and oral administration of ondansetron hydrochloride on chemotherapy-induced nausea and vomiting in patients with esophageal cancer].

The effects of ondansetron hydrochloride (OND) were studied through 11 courses of chemotherapy, including 70 mg/m2 of cisplatin, in 9 patients with advanced esophageal cancer. During the observation period of 5 days, 4 mg of OND was given intravenously on the day of cisplatin infusion and orally for consecutive 4 days, and nausea was controlled by over 70%. Vomiting was controlled by over 80%. The inhibitory effect of OND on nausea and vomiting was found in 72.7% on the day of cisplatin injection and 88.9% overall. No other side effects of OND except slight increases in total bilirubin and LDH were found in any patient. These findings suggest that intravenous and oral administration of OND may inhibit chemotherapy-induced nausea and vomiting in patients with advanced esophageal cancer.

Combined modality therapy for basaloid squamous carcinoma of the esophagus.

A 61 year-old woman came to our hospital with dysphasia that had persisted for 2 months. Endoscopy and barium swallow showed a protruding tumor, about 6.0 cm long, in the midportion of the esophagus. A biopsy specimen showed squamous cell carcinoma of the esophagus. Computed tomography (CT) scan revealed adventitial involvement and lymph node metastases beneath the carina. After 2 courses of chemotherapy with cisplatin (CDDP) 100 mg for 1 day, 5-Fluorouracil (5-FU) 800 mg for 5 days, and leucovorin 30 mg for 5 days, complete regression of the tumor was observed by endoscopy and barium esophagography. Transthoracic esophagectomy with lymph node dissection was performed. Histologically, the muscle layers of the resected esophagus had been replaced by fibrous tissue; however, small foci of basaloid squamous carcinoma (BSC) were found in the submucosa. Six months after surgery, a CT scan revealed a metastatic lymph node around the right main bronchus. Chemotherapy and radiotherapy resulted in the disappearance of the metastasis. The patient has survived for more than 3 years since surgery with a good quality of life.