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Biomedical subjects

K Sasajima

Publications and source records attributed to K Sasajima.

At least 19 recordsLinked to original sources

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.

Aged↗

Serum level of cytokeratin 19 fragment (CYFRA 21-1) indicates tumour stage and prognosis of squamous cell carcinoma of the oesophagus.

To determine the clinical efficacy of serum concentration of cytokeratin 19 fragment (CYFRA 21-1), sera from 66 patients with oesophageal squamous cell carcinoma were examined, and 54 surgically resected specimens were immunohistochemically stained for cytokeratin 19 (CK-19). The patients with positive CK-19 staining in the tissues of their carcinomas had significantly higher serum CYFRA 21-1 levels compared with those with negative CK-19 staining. When the cut-off value was defined as 2.0 ng/mL, CYFRA 21-1 had a higher positive ratio than that of either squamous cell carcinoma antigen (SCC-Ag) or carcinoembryonic antigen (CEA). Serum CYFRA 21-1 level increased significantly along with the clinical stages. In addition, serum CYFRA 21-1 level served as a prognostic factor for patients with oesophageal carcinoma after surgery, whilst SSC-Ag and CEA is not connected with the outcome. These findings suggest that the serum CYFRA 21-1 probably originated from the tumour tissue is an important marker for determining the stage and outcome of oesophageal carcinoma.

Adult↗

Primary undifferentiated small cell carcinoma of the esophagus.

We histologically examined undifferentiated small cell carcinoma of the esophagus from 21 patients and used immunohistochemical methods for detection of chromogranin A and p53, bcl-2, and Rb oncoproteins. Nine (43%) of the 21 carcinomas consisted solely of undifferentiated cells, but heterogeneous components of in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma were observed in the other 12 (57%) tumors. Squamous cell carcinoma in situ was observed in the mucosa adjacent to the main tumor in 7 (50%) of the 14 resected esophageal specimens. An admixture of invasive squamous cell carcinoma and undifferentiated carcinoma was observed in 4 (19%) of the 21 tumors, and mucoepidermoid carcinoma was noted in one case. Chromogranin A staining yielded a positive reaction in two (10%) undifferentiated components but was negative in all heterogeneous components. Multiple sites of p53 immunopositivity were seen in the undifferentiated component of 17 (81%) of the 21 tumors, as well as in the in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma components of 9 (75%) of 12 tumors. Seven (33%) of the 21 tumors showed positive bcl-2 immunoreactivity in the small cell component, but all of the heterogeneous components were negative. Rb protein immunoreactivity was observed in the small cell component of one (5%) case and in 9 (75%) of the 12 heterogeneous components. Six (86%) of the seven in situ squamous cell carcinoma components were positive for Rb protein. Eighteen (86%) of the 21 patients died within 24 months of diagnosis. Two patients (10%) who survived for more than 24 months had received chemotherapy.

Aged↗

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.

Adult↗

[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.

Administration, Oral↗

Glucocorticoid attenuates a decrease of antithrombin III following major surgery.

BACKGROUND: Major surgery, such as esophagectomy, activates inflammatory responses and the coagulation system, and this activation is characterized by release of inflammatory cytokines and a decrease in antithrombin-III (AT-III), respectively. Preoperative glucocorticoid administration has been reported to suppress circulatory cytokine levels after major surgery. PATIENTS AND METHODS: A total of 28 patients underwent esophagectomy for esophageal carcinoma; 14 of them were given 10 mg/kg of methylprednisolone intravenously upon induction of anesthesia and 14 served as controls. Circulating levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), polymorphonuclear (PMN) elastase, thrombin-antithrombin III complex (TAT), AT-III, and albumin were measured before and immediately after the operation and on postoperative days (PODs) 1, 3, 5, and 7. RESULTS: TNF-alpha, IL-6, and TAT levels significantly increased after esophagectomy in both groups. AT-III and albumin decreased to their minimum levels on POD 1 and POD 3, respectively. Methylprednisolone treatment effectively inhibited the increases in TNF-alpha and IL-6 and the decreases in AT-III and albumin, but did not inhibit the increases in PMN-elastase and TAT levels. There were significant correlations between AT-III, IL-6, and albumin levels. CONCLUSIONS: These results suggest that methylprednisolone pretreatment attenuates the decrease in AT-III by reducing IL-6 production postoperatively.

Aged↗

Systemic and pulmonary responses of inflammatory cytokines following esophagectomy.

Inflammatory cytokines in plasma and bronchoalveolar lavage fluid (BALF) from 16 post-esophagectomy patients with and without preoperative methylprednisolone administration were studied. Interleukin-8 (IL-8), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) concentrations in plasma and BALF were measured by ELISA immediately after surgery (0-POD) and on the postoperative day 1 (1-POD). In patients without methylprednisolone treatment, IL-8 levels in BALF were 362 +/- 67 pg/ml on 0-POD and 948 +/- 359 pg/ml on 1-POD, and were approximately 10 times higher than those in plasma levels. IL-6 levels in plasma were significantly higher than those in BALF. The TNF-alpha concentration was similarly low in plasma and BALF. The patients with preoperative methylprednisolone treatment had significantly lower IL-8 levels in BALF and plasma compared with the patients without the treatment. Immunocytochemically, each cytokine was identified in the cytoplasm of bronchoalveolar macrophage. The percentage of polymorphonuclear cells (PMN) among BAL cells was significantly increased on 1-POD when compared with that of 0-POD, and tended to be decreased by preoperative methylprednisolone treatment. These results suggest that IL-6 was markedly increased in the peripheral circulation and that increased pulmonary IL-8 might be related to an accumulation of PMN in the lung under surgical stress. Further, methylprednisolone administration could possibly reduce postoperative cytokine responses at the local and systemic levels.

Adult↗

[A case report of esophageal carcinoma with grade 3 response by preoperative chemotherapy using CDDP/5-FU/LV].

A 67-year-old man was diagnosed as having a type 3 advanced esophageal carcinoma by barium swallow and endoscopy. Biopsy specimens showed well-differentiated squamous cell carcinoma with positive immunostaining for p53, C-erb B-2 and negative for bcl-2. Two courses of chemotherapy using 5-FU, leucovorin and CDDP were performed before operation. Because no cancer cells were present in the surgical specimens, the effect was evaluated as grade 3. This neoadjuvant chemotherapy may be effective for esophageal carcinoma with a possible apoptosis mechanism.

Aged↗

[Pathology of the cardia].

Defining the cardia as consisting of 2 cm of the distal esophagus and 2 cm of the proximal stomach, we describe the detailed histopathological features of the cardia and esophagogastric junction (EGJ). The distance between the EGJ and the squamocolumnar junction (SCJ) was 0-10 mm (mean: 3 mm) in 50 Japanese autopsy cases, but the SCJ was not located below the EGJ. It has been reported that pancreatic metaplasia, small leiomyomas, inflammatory EGJ polyps, carditis, and Barrett's epithelium are often recognizable in the cardia, and the literature on these conditions is reviewed. The relationship between leiomyomas and gastrointestinal stromal tumors is also reviewed, and the histopathology of short-segment Barrett's esophagus is described. In biopsy specimens obtained from Barrett's esophagus, the presence of ducts of esophageal glands proper in the metaplastic mucosa as revealed by microscopy can be used to establish the diagnosis, although only in a short-segment of Barrett's esophagus less than 3 cm in length. Finally, several English and Japanese textbooks on the pathology of the digestive tract containing descriptions of normal and diseased cardia are described for the convenience of authors writing scientific papers on diseases of the cardia.

Aged↗

Telomerase activity in esophageal carcinoma.

BACKGROUND AND OBJECTIVES: Telomerase is a ribonucleoprotein that synthesizes telomeric DNA. Immortalized and carcinoma cells show no loss of telomere length during cell division. Telomerase activity has been demonstrated in carcinomas of various organs, but not in nonneoplastic tissues. In patients with esophageal carcinoma, no data have been reported concerning the relationship between telomerase activity and clinicopathological findings. MATERIALS AND METHODS: Esophageal carcinomas from 31 patients and normal esophageal mucosae from 92 patients were examined. Telomeric Repeat Amplification Protocol assay to detect telomerase activity and Southern blot analysis to examine telomere length were performed. RESULTS: Of the 31 carcinomas, 27 (87%) had detectable telomerase activity. Twenty-one (23%) of the 92 normal esophageal mucosae from autopsied patients also had detectable telomerase activity. There was no difference between stage and outcome and absence or presence of telomerase activity. No difference in terminal restriction fragment (TRF) length was observed between carcinomas with and without telomerase activity. CONCLUSION: Telomerase activity was demonstrated in a considerable number of normal esophageal mucosae. This suggests the possibility of a high frequency of false positivity if the presence of telomerase activity alone is used as a tumor-specific marker.

Adenocarcinoma↗

Endoscopic dexamethasone injection following balloon dilatation of anastomotic stricture after esophagogastrostomy.

BACKGROUND: Anastomotic stricture is common after esophagogastrostomy. Recent advances in nonsurgical treatment include the silicon bougie and balloon dilatation. However, simple dilatation alone with a silicon bougie or endoscopic balloon dilator was repeated a mean of 4.7+/-5.4 times to control anastomotic stricture because of its temporary effect. METHODS: For 11 patients, endoscopic injection of dexamethasone (8 mg) around the anastomosis was done immediately after balloon dilatation (40 psi for 5 minutes). RESULTS: This method significantly reduced the number of the dilatations to 1.1+/-0.3 (P < 0.05). Ten of the 11 patients did not need any further treatment. There were no side effects or complications of dexamethasone injection. CONCLUSION: A combination of endoscopic balloon dilatation and dexamethasone injection provided an easy and safe method for preventing the recurrence of anastomotic stricture.

Anastomosis, Surgical↗

The effect of preoperative high dose methylprednisolone in attenuating the metabolic response after oesophageal resection.

OBJECTIVE: To evaluate the effect of giving glucocorticoids preoperatively for the prophylaxis of surgical stress. DESIGN: Prospective randomised study. SETTING: University hospital, Japan. SUBJECTS: 30 patients undergoing resection of oesophageal carcinoma. INTERVENTIONS: 15 patients (group 1) were randomised to be given methylprednisolone (30 mg/kg) and 15 patients (group 2) to be given saline intravenously before operation. MAIN OUTCOME MEASURES: Outcome, length of stay in the intensive care unit (ICU), metabolic response, and oxygenation. RESULTS: Patients given methylprednisolone had a mean stay in the ICU of 5.1 +/- 1.0 days compared with 8.2 +/- 4.5 days in the saline group (p < 0.01). 5 patients in the saline group compared with 0 in the methylprednisolone group developed postoperative complications (p = 0.02). Plasma norepinephrine and arginine vasopressin levels in methylprednisolone group were significantly lower than those in the saline group (p < 0.05). The PaO2:FiO2 ratio in the saline group was significantly lower than that in the experimental group (p < 0.01). CONCLUSIONS: Preoperative methylprednisolone may facilitate the postoperative management of surgical patients.

Adult↗

Changes in urinary nitrate and nitrite during treatment of ulcerative colitis.

The urinary excretion rates of nitrate (NO3) and nitrite (NO2) were monitored in 14 patients with active ulcerative colitis during treatment using hydrocortisone and sulfasalazine. During the active phase of the disease, the NO3 excretion was significantly higher in the patients than in healthy controls (n = 6, p < 0.05), although it varied considerably among the patients. During the healing phase, the NO3 excretion decreased concurrently with improvement of symptoms and colorectal ulceration, but the NO2 excretion increased. During the inactive phase of the disease, the NO3 and NO2 excretions were significantly lower than during the active phase, and the NO2/NO3 ratio resembled that in the healthy controls. In contrast, a patient who failed to respond to treatment showed continuously high NO3 and NO2 excretion rates. These results indicate that urinary NO3 and NO2 excretions vary with the disease state in ulcerative colitis.

Adult↗

Increases in pulmonary artery pressure and cardiac output due to the inhibition of nitric oxide synthesis during operative stress.

Pulmonary artery pressure (PAP), cardiac output (CO), and urinary nitrate, a stable endproduct of nitric oxide (NO), were measured pre- and postoperatively in eight patients who underwent esophagectomy for squamous cell carcinoma of the thoracic esophagus. A significant elevation of PAP and CO on the day of operation (POD 0) was accompanied by a low concentration of urinary nitrate. A reduction in PAP and CO, and an increase in nitrate to the preoperative levels, were found on PODs 2 and 3, respectively, but urinary nitrate decreased again after POD 3. Consequently, the changes in PAP and CO were closely correlated with the nitrate concentration. These results suggest that operative stress inhibited NO synthesis with a transitory induction of endogenous NO synthesis postoperatively.

Aged↗

Adenoma accompanied by superficial squamous cell carcinoma of the esophagus.

BACKGROUND: Adenoma of the esophagus is a rare type of esophageal submucosal tumor. METHODS: An immunohistochemical and histopathologic study is reported of specimen from a patient with adenoma of the esophagus. RESULTS: The eighth reported case of esophageal submucosal adenoma without Barrett epithelium is described. The patient was a 58-year-old man with an adenoma and carcinoma of the esophagus. The adenoma showed papillotubular structures lined with two layers of cuboidal cells within the submucosa and lamina muscularis mucosae, and the carcinoma was of the superficial squamous cell type confined to the submucosa. CONCLUSIONS: Morphologic findings suggested that this adenoma had originated from the duct of the esophageal gland proper.

Adenoma↗

Multiple polyps of esophagus, stomach, colon, and rectum accompanying rectal cancer in a patient with constitutional chromosomal inversion.

BACKGROUND: It has been reported that colorectal carcinomas are caused by a multistage process. In patients with familial adenomatous polyposis, carcinoma of the colorectum frequently develops and occasionally polyps develop in the upper gastrointestinal tract. Chromosomal deletion often is found for chromosomes 5, 17, and 18, on which tumor suppressor genes are located. Furthermore, loss of the alleles of loci on chromosome 3 has been reported in renal cell carcinoma, small cell lung carcinoma, and mixed salivary gland tumor in hereditary and sporadic cases. These data support the concept of a recessive mechanism for the development of human tumors. PATIENTS AND RESULTS: The authors report the case of a 48-year-old woman with rectal cancer accompanied by multiple polyps in the esophagus, stomach, and colorectum. Histologically, the polypoid lesions in the esophagus, stomach, and colorectum showed a thickened mucosa, hyperplastic polyps, and mixed hyperplastic adenomatous polyps, respectively. Karyotype analysis showed 46, xx, inv(3)(p12.2q25.3) in all 20 inspected peripheral lymphocytes. By Southern blot with a c-raf probe, one allele of the c-raf-1 gene, which has been mapped on chromosome 3p25, was deleted from the rearranged chromosome 3 in the peripheral lymphocytes, intact colonic mucosa, and cancer tissue. CONCLUSIONS: These results suggest that the development of hyperplastic polyps and carcinoma of the rectum results from the allelic loss in chromosome 3p, as has been reported for solid tumors at other sites.

Chromosome Aberrations↗