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Biomedical subjects

Akira Tokunaga

Publications and source records attributed to Akira Tokunaga.

At least 19 recordsLinked to original sources

Simple and accurate (13)C-urea breath test for detection of Helicobacter pylori in the remnant stomach after surgery.

BACKGROUND: The efficacy of the (13)C-urea breath test (UBT) for diagnosis of Helicobacter pylori (H. pylori) infection in the remnant stomach after surgery is a matter of controversy. We report a simple and accurate method of (13)C-UBT for diagnosis of H. pylori infection in the remnant stomach after gastrectomy. METHODS: Eighty patients who had undergone gastrectomy with or without subsequent H. pylori eradication therapy were examined a total of 134 times for H. pylori infection by the (13)C-UBT. (13)C-Urea, 10mg per test, was used in powdered form or in the form of film-coated tablets. Breath samples were collected before and 10, 20, and 3 min after ingestion. Mucosal biopsy specimens for bacterial culture and histological examination of the remnant stomach were collected endoscopically after each (13)C-UBT test. RESULTS: Factors that confounded the (13)C-UBT results in the remnant stomach were oral bacteria, posture, and residual food. Lying horizontally on the left side was the best position, and film-coated tablets indicated no necessity for use of mouthwash. The method of anastomosis had no significant effect on the results of the (13)C-UBT. Thirty minutes and a cutoff of 4.5 per thousand were optimal conditions for detection of H. pylori in the remnant stomach. Under these conditions, sensitivity, specificity, and accuracy were 79.4% (27/34 cases), 95.7% (44/46 cases), and 88.8% (71/80 cases), respectively, in ordinary H. pylori diagnosis, and 100% (2/2 cases), 93.3% (14/15 cases), and 94.1% (16/17 cases), respectively, in evaluating eradication at 4 weeks after treatment of H. pylori. CONCLUSIONS: Having the patient lie horizontally on the left side, using a film-coated (13)C-urea tablet without using mouthwash, and measurement at 3 min provided a simple and accurate method of (13)C-urea breath test for detection of H. pylori in the remnant stomach after gastrectomy.

Aged↗

Factor XIII therapy of anastomotic leak, and circulating growth factors.

Wound healing is far more rapid in the gastrointestinal tract than in the skin. Once dehiscence of a surgical anastomosis in the gastrointestinal tract occurs, the high collagenase activity in the gastrointestinal tract may delay wound healing and promote the formation of a nonhealing fistula. Because factor XIII promotes cross-linking of fibrin during the early phase of wound healing, we investigated the effect of factor XIII concentrate on 16 anastomotic leaks and a nonhealing fistula. A 240-U dose of factor XIII concentrate (Fibrogammin P) was administrated intravenously for 5 days. Factor XIII activity and plasma levels of epidermal growth factor (EGF), transforming growth factor (TGF)-beta, and interleukin-6 were measured before treatment and 1 day and 7 days after the end of treatment. Clinical outcomes were evaluated on the basis of the findings of contrast radiography, computed tomography, and drainage volume. Improvement relevant to the therapy was observed in 15 cases (88.2%). Factor XIII activity increased to more than 70% of the normal value in 11 cases (64.7%) but remained at 40% to 70% of the normal value in 6 cases (35.3%). Plasma EGF and TGF-betalevels increased in patients with improvement but were unchanged in patients without improvement. Our findings suggest that factor XIII significantly accelerates wound healing of anastomotic leaks and nonhealing fistulas by increasing circulating growth factors after systemic administration.

Aged↗

Laparoscopic surgery for gastric cancer: 5 years' experience.

The purpose of this study was to clarify the safety and value of laparoscopic surgery for gastric cancer. This retrospective study involved 101 patients with gastric cancer treated with laparoscopic surgery at the Nippon Medical School Hospital from February 2001 through July 2005. The following variables were evaluated: age, sex, comorbid conditions, tumor size, location, gross type, histological type, depth of wall invasion, and presence or absence of lymph node metastasis. The surgical variables investigated included operating time, blood loss, postoperative complications, and length of postoperative stay. Mean tumor diameter was 24.1 +/- 18.4 mm, and most tumors were located in the lower third of the stomach. Endoscopic examination revealed that 98 of the tumors were early gastric cancers. The mean operation time was 255 +/- 74 min, and mean blood loss was 128 +/- 162 g. Local gastrectomy without lymphadenectomy was performed in 13 cases, and pylorus-preserving gastrectomy with perigastric lymphadenectomy was performed in 16 cases. Distal gastrectomy with systemic lymphadenectomy was performed in 56 cases. Proximal or total gastrectomy with lymph node dissection for tumors located in the upper half of the stomach was performed in 16 cases. The mean postoperative hospital stay was 13.3 +/- 7.6 days. No patients died during the admission. Postoperative surgical complications occurred in 10 patients (10%) and consisted of anastomotic bleeding in 3 patients, pneumohypoderma in 1 patient, and remote infection in 6 patients. The only medical complication was a stroke in 1 patient. We conclude that laparoscopy-assisted gastrectomy is a safe and useful operation for most early gastric cancers. If patients are selected properly, laparoscopy-assisted gastrectomy can be a curative and minimally invasive treatment for gastric cancer.

Adult↗

Helicobacter pylori infection with a duodenal ulcer in a 6-year-old boy.

A 6-year-old boy was hospitalized because of dark feces and facial pallor of 1 weeks duration. Other gastrointestinal symptoms, including vomiting and abdominal pain, were absent, but he felt dizziness when standing and fatigue on effort. Hematologic studies revealed iron-deficiency anemia, and endoscopy showed gastric erosions and a duodenal ulcer. All test results for Helicobacter pylori infection, including H. pylori antigen in stool, anti-H. pylori IgG immunoassay in serum, and the (13)C-urea breath test, were positive. Because an H. pylori-associated gastric ulcer had been diagnosed with endoscopy in the patients father 3 years earlier, father-son transmission was suspected. The patient was treated with triple-agent eradication therapy (proton pump inhibitor [lansoprazol], amoxicillin, and clarithromycin) for 2 weeks. One month after therapy was completed, eradication of H. pylori was confirmed by negative results on the stool antigen test. Peptic ulcer disease can occur in young children, as in this case. The stool antigen test kit is a useful and reliable method that can be used even in preschool children to diagnose H. pylori infection.

Child↗

Expression of keratinocyte growth factor receptor correlates with expansive growth and early stage of gastric cancer.

The keratinocyte growth factor receptor, also known as KGFR/FGFR2 IIIb, is mainly localized in epithelial cells, and participates in the proliferation of these cells. In contrast, a recent study has revealed that the overexpression of KGFR in salivary adenocarcinoma induces growth inhibition, cell differentiation and apoptosis. We attempted to clarify the expression and role of KGFR in normal and cancerous human gastric tissues and cancer cell lines. Reverse-transcription polymerase chain reaction and Western blot analyses showed KGFR mRNA and its protein expression in NUGC-4, KATO-III and MKN-7 gastric cancer cell lines, but not in the NS-8 cell line. Immunohistochemically, KGFR immunoreactivity was weakly detected in the luminal surface of normal gastric epithelial cells. In addition, KGFR immunoreactivity was strongly detected in the nucleus and cytoplasm of many parietal cells. In gastric cancer tissue, KGFR was expressed in the cell membrane and cytoplasm of cancer cells in 46 of 126 (36.5%) cases. KGFR expression in gastric cancer cells was significantly associated with early-type macroscopic findings, shallow invasion of the gastric wall and expansive growth type. KGFR expression tended to correlate with a good prognosis in gastric cancer. These findings indicate that KGFR expression plays important roles in the differentiation of normal gastric epithelial cells and parietal cell functions. Furthermore, a decreased expression level or the non-expression of KGFR in gastric cancer cells may be associated with the proliferation and invasion of gastric cancer cells and a poor prognosis for the patient.

Adult↗

[A case of advanced gastric cancer successfully treated by TS-1 and CDDP after jejunostomy].

A 65-year-old female with unresectable advanced gastric cancer accompanied by multiple lung metastases underwent jejunostomy and was treated with TS-1 and CDDP. One course consisted of TS-1 (80 mg/day) via an intestinal fistula tube from days 1 to 14 followed by 14 days rest and CDDP (80 mg/day) was administered by 24-hour continuous intravenous infusion on day 8. After 3 courses, the primary tumor and lymph node metastases decreased in size (PR), and CT scan showed the multiple lung metastases had disappeared. Total gastrectomy (D 2) and splenectomy were performed after chemotherapy. The final diagnosis was Stage IIIA and the pathological response to chemotherapy was Grade 2. The patient has survived for over 14 months after surgery and has presented no signs of recurrence.

Aged↗

Lipid-lowering effect of monascus garlic fermented extract (MGFE) in hyperlipidemic subjects.

Monascus Garlic Fermented Extract (MGFE) is a unique material produced from garlic fermented using Monascus pilosus, which contains characteristic compounds such as dimerumic acid and monacolin K. In this study, we examined the effect of MGFE on hyperlipidemic subjects. Fifteen subjects aged 33-59 years (11 men and 4 women) participated. All the subjects had either hypercholesterolemia (> or = 220 mg/dl) or hyper-low-density lipoprotein cholesterolemia (> or = 140 mg/dl), but only 4 of the 15 (27%) were hypertriglycemic (> or = 150 mg/dl). All subjects received two capsules of MGFE (225 mg/capsule) after breakfast and dinner for 4 weeks. After an overnight fast, blood was taken 0, 2 and 4 weeks after the start of MGFE intake, and 2 weeks after MGFE withdrawal. MGFE significantly reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol levels 2 and 4 weeks after the start of MGFE intake as compared with the baseline. Although the level of high-density lipoprotein cholesterol (HDL-C) was unaffected at any time, the atherogenic index calculated from the value of TC and HDL-C was significantly reduced 2 and 4 weeks after the start of MGFE intake. These effects of MGFE tended to disappear within 2 weeks after withdrawal. Triglyceride (TG) and lipid peroxide levels were not reduced dramatically, but TG levels in hypertriglycemic subjects tended to reduce as compared with the baseline value. No abnormal changes in blood biochemical parameters or adverse effects were observed in any of the subjects. Our present results indicate that MGFE attenuates hyperlipidemia, suggesting that MGFE is a potent agent for preventing arteriosclerotic diseases.

Adult↗

Postoperative changes in body composition after gastrectomy.

Nutritional status is one of the most important clinical determinants of outcome after gastrectomy. The aim of this study was to compare changes in the body composition of patients undergoing laparoscopy-assisted gastrectomy (LAG), distal gastrectomy (DG), or total gastrectomy (TG). Total body protein and fat mass were measured by performing a multifrequency bioelectrical impedance analysis using an inBody II machine (Biospace, Tokyo, Japan) in 108 patients (72 men, 36 women) who had undergone LAG (n=24), DG (n=39), or TG (n=45). Changes between the preoperative data and results obtained on postoperative day 14 and 6 months after surgery were then evaluated. The mean preoperative body weight of the subjects was 57.6+/-10.7 kg, the mean body mass index was 22.5+/-3.4 kg/m(2), and the mean fat % was 24%+/-7%. In the immediate postoperative period (14 days), the body weight loss in the LAG group was significantly lower than in the DG and TG groups (2.5+/-0.9 kg vs. 3.5+/-1.8 kg and 4.0+/-1.9 kg, respectively; P < 0.0001). The body composition studies demonstrated a loss of total body protein rather than fat mass. Six months after surgery, body weight was not significantly different from preoperative values in the LAG and DG groups (-1.2+/-3.8 kg and -1.8+/-4.7 kg, respectively), but had decreased by 8.9+/-4.9 kg in the TG group (P=0.0003). A body composition analysis revealed a loss of fat mass in the DG and TG groups. The patients who underwent gastrectomy lost body protein mass during the early postoperative period. The type and extent of surgery has an effect on long-term body mass and composition. Bioelectric impedance analysis can be used to assess body composition and may be useful for nutritional assessment in patients who have undergone gastrectomy.

Aged↗

Keratinocyte growth factor receptor expression in normal colorectal epithelial cells and differentiated type of colorectal cancer.

The keratinocyte growth factor receptor, also known as KGFR/FGFR2 IIIb, is mainly localized in epithelial cells and participates in the proliferation of these cells. In the present study, we attempted to clarify the expression and role of KGFR in human colorectal cancer. The KGFR protein was detected in several colorectal cancer cell lines. Immuno-histochemically, KGFR was expressed on the luminal surface of epithelial cells in normal colorectal tissues. KGFR was expressed in 35 of 56 (62.5%) colorectal cancer patients and localized at the center of the cancer nests. Cytokeratin 20 (CK 20) colocalized with KGFR. In contrast, Ki-67 localized at the periphery of the cancer nests. Clinicopathologically, a high level of KGFR expression was associated with well-differentiated histological type (p<0.0001) and shallow wall invasion (p<0.0174). These findings indicate that KGFR may play important roles in the differentiation of normal colorectal epithelial cells and establishment of the well-differentiated histological type of colorectal cancer cells.

Aged↗

Inflammation of the gastric remnant after gastrectomy: mucosal erythema is associated with bile reflux and inflammatory cellular infiltration is associated with Helicobacter pylori infection.

BACKGROUND: Controversy exists concerning the role of bile reflux and Helicobacter pylori ( H. pylori) infection in the development of inflammation of the gastric remnant after gastrectomy. This study was designed to investigate association of bile reflux and H. pylori infection or both with inflammatory changes in the gastric remnant. METHODS: A questionnaire on GI symptoms was returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of H. pylori infection and chronic, active inflammatory cellular infiltration in the biopsy specimens were examined microscopically with the updated Sydney system. RESULTS: No difference in the incidence of GI symptoms was observed among individual gastrectomy patients. Bile reflux was lower in patients who had undergone a gastrectomy with jejunal interposition, a pylorus-preserving gastrectomy, and a gastrectomy with Roux-Y anastomosis than those who had undergone a Billroth-II (B-II) anastomosis ( P < 0.05). Endoscopy showed positive correlation between mucosal erythema and bile reflux ( P < 0.001). No correlation was observed between the mucosal erythema and chronic and active inflammatory cellular infiltration. Infection of H. pylori correlated with chronic and active inflammatory cellular infiltration ( P < 0.001). Bile reflux did not correlate with the severity of chronic and active inflammatory cellular infiltration or H. pylori infection. CONCLUSIONS: Bile reflux into the gastric remnant was observed by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell infiltration in the gastric remnant after gastrectomy may be caused by bile reflux or H. pylori infection, respectively.

Bile Reflux↗

Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue.

In vitro studies suggest that cyclooxygenase-2 (COX-2) induces angiogenesis by stimulating angiogenic growth factors while inhibiting apoptosis in cancer cell lines. A series of 107 gastric adenocarcinoma cases that had undergone gastrectomy was studied to determine the correlation between COX-2 expression, angiogenesis, and apoptosis in human gastric cancer tissue. COX-2, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and Bcl-2 were stained by single and dual immunoassaying methods. Microvessel density was determined by immunostaining for CD34. Apoptosis was evaluated with the TUNEL assay. COX-2 expression was positive exclusively in cancer cells in 46 cases (43%). COX-2 expression significantly correlated with VEGF and PDGF expression. Dual staining for COX-2 and VEGF showed that colocalization of these proteins was most frequent at the advancing edge of cancer cells. Microvessel density was higher in COX-2-and VEGF-positive cases than in COX-2- and VEGF-negative cases. In addition, COX-2 expression correlated with Bcl-2 expression. The apoptotic index was lower in COX-2-positive cancer cells than in COX-2-negative cases. Multivariate analysis revealed that coexpression of COX-2 and VEGF, age, lymph node status, and serosal invasion were independent prognostic factors for overall survival in gastric cancer patients. Therefore, these data suggest that COX-2 contributes to gastric cancer development by promoting angiogenesis and inhibiting apoptosis.

Adenocarcinoma↗

Tissue distribution after intravenous dosing of micafungin, an antifungal drug, to rats.

The tissue distribution after an intravenous dose of micafungin (1 mg/kg), a new echinocandin-like lipopeptide antifungal agent, to male rats was investigated. Micafungin in plasma disappeared biexponentially with a terminal half-life of 5.03 h. Micafungin concentrations in liver, kidney, and lung at the first sampling time (5 min) after dosing were 1.15, 1.64, and 2.58-fold higher than the plasma concentration, and the AUC(0- infinity ) were 1.61, 3.42, and 2.89-fold higher than that for plasma. The terminal half-lives for these tissues were 5.14, 4.87, and 5.31 h, respectively, which were comparable to those for plasma. These results suggest that micafungin distributes rapidly and moderately into tissues such as the liver, kidney, and lungs, and that the concentrations in tissues decreased in parallel with the unchanged drug in plasma.

Animals↗

A case report of duodenal carcinoid tumor associated with early gastric cancer.

A rare case of carcinoid tumor in the duodenal bulb associated with early gastric carcinoma is reported. An 85-year-old asymptomatic male was admitted to our hospital, referred by his neighboring doctor because of early gastric carcinoma shown by endoscopic examination. X-ray studies of the upper gastrointestinal tract showed irregular lesser curvature of the gastric antrum and a filling defect (phi1 cm) at the duodenal bulb. Gastric biopsy revealed the histological findings of Group V. Distal gastrectomy including the duodenal bulb with D2 lymph node dissection was performed. A resected specimens showed superficial depressed type carcinoma at the lesser curvature of the antrum, and an isolated submucosal tumor of 7x7 mm in size at the duodenal bulb. Histological examination disclosed papillary adenocarcinoma in the gastric mucosa and a carcinoid tumor of the duodenal bulb in the submucosal layer without high malignant findings. The patient has been well for 5 years since the surgery. In conclusion, we discussed 46 collected cases of carcinoid tumor of the duodenum associated with gastric carcinoma in Japan. Preoperative diagnosis of carcinoid tumor of the duodenum is very difficult, and thorough examinations are needed for submucosal lesion.

Adenocarcinoma, Papillary↗

Implementation of the diagnosis procedure combination in specific-function hospitals.

A Nobel medical payment system, the Diagnosis Procedure Combination (DPC), was implemented in Nippon Medical School Hospital and 81 other specific-function hospitals in 2003. This payment system depends on the length of hospital stay and diagnosis and medical procedures, and differs from the existing payment system, which depends on a piece rate. The daily payment differs for among almost 2,500 groups of DPC defined by the International Statistical Classification of Diseases and Related Health Problems (ICD-10), and procedures, such as operations (K and J codes of the existing payment system). One of the most important outcomes may be a decrease in lengths of hospital stay, because the range of mean lengths of stay in specific-function hospitals has been officially stated to be 14 to 30 days, and the difference between the longest and shortest mean is almost double. The new medical payment system should stimulate competition among hospitals. In order to decrease the length of stay, we developed clinical pathways for patients undergoing surgery, such as laparoscopic cholecystectomy, gastrectomy, and inguinal hernia operations, as well as clinical protocols for the surgical procedures, such as percutaneous transhepatic cholangiodrainage (PTCD) and percutaneous endoscopic gastrostomy (PEG). Health care is undergoing a challenging transition, and we must improve patient care and clinical practice.

Critical Pathways↗

Helicobacter pylori eradication therapy for the remnant stomach after gastrectomy.

BACKGROUND: The remnant stomach after surgery for gastric cancer is at high risk for the metachronous development of multiple gastric cancers. Here, we report on eradication therapy of Helicobacter pylori in the remnant stomach, comparing the eradication rate with that in unoperated stomachs. We examined gross and histological changes after treatment. METHODS: Forty H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based dual and triple therapies. After eradication, histological changes were classified on the basis of the updated Sydney system. RESULTS: The eradication rate in the remnant stomach was 70% (14 of 20) after dual therapy and 90% (18 of 20) after triple therapy, using per-protocol analysis, and these rates were comparable to the rates of 70% (186 of 264) and 88% (58 of 66), respectively, in nonsurgery patients. After eradication, three sites in the remnant stomach showed similar histological changes: significant decreases in inflammation and activity scores (P < 0.001) and no significant changes in glandular atrophy and intestinal metaplasia scores. CONCLUSION: PPI-based therapy was as effective for H. pylori eradication in the remnant stomach as in the unoperated stomach, and eradication therapy resulted in a significant decrease in inflammatory cell infiltration of the mucosal layer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Clinical significance of a standardized clinical pathway in gastrectomy patients].

UNLABELLED: In traditional practice patterns, physicians take care of all clinical decisions, such as diagnosis, treatment, and recovery. In the Nippon Medical School Hospital a clinical pathway for distal gastrectomy patients, recorded as a post-operative care map, was introduced in August 2000. In January 2001 the post-operative management was analyzed and standardization of practice was carried out with printed order sets, such as drugs and infusion solutions. The aim of this study was to evaluate the clinical significance of the clinical pathway for gastrectomy patients by employing standardized postoperative management and printed order sets. PATIENTS AND METHODS: From January 2001 to December 2001, 87 patients underwent distal (43), total (28), proximal (7) and partial gastrectomy (9) for gastric cancer (stage IA: 47, IB: 9, II: 7, IIIA: 8, IIIB 2, IV: 10) and gastrointestinal stromal tumor (4). These patients were randomly assigned to either the main building or the east building of our hospital. In the main building 38 patients were looked after using traditional practice (control group). In the east building 47 patients were looked after according to the clinical pathway (path group) and 2 patients were excluded from the path group because of neo-adjuvant chemotherapy and severe heart failure. Aspects of the patients' outcomes, including length of stay, the first day of the diet, morbidity, and medical costs, were compared between the path group and the control group. All data were expressed as means+/-standard deviation. Statistical analyses were made using Student t-test, Mann-Whitney U-test, and chi(2) test, and the 5%level was chosen for statistical significance. RESULTS: The length of the hospital stay was 27.1+/-10.0 and 40.8+/-26.1 days (p<0.005) and the length of post-operative stay was 18.1+/-9.5 and 28.2+/-22.3 days (p<0.01) in the path group and the control group, respectively. The post-operative day when the diet was started for the path and control groups was 6.8+/-8.9 and 8.2+/-7.2, respectively; however, the length of the intravenous infusion for the two groups was 11.8+/-1.1 and 16.5+/-1.2 days (p<0.01), respectively. There was no statistically significant difference in the morbidity rate between the path group (3/47) and the control group (5/38). The total cost was 1,502,587 yen +/-41,650 in the path group and 1,932,197 yen +/-131,030 in the control (p<0.001). CONCLUSION: A clinical pathway for gastrectomy patients proved useful to optimize their postoperative care, including medication management and diet education. It is suggested that the implementation of a standardized clinical pathway for gastrectomy patients reduced the length of the hospital stay and the medical costs.

Critical Pathways↗

[An economic evaluation on the clinical pathway for gastrectomy].

OBJECTIVE: To analyze the costs of gastrectomy patients treated with the clinical pathway. PATIENTS AND METHODS: Seventy-six patients (path group 44, control 32) had undergone gastrectomy in our hospital in 2001. The clinical pathway included the same care map. Treatment costs were estimated from medical cost receipt data. The economical analysis was performed from the point of the direct cost payer's view. RESULTS: The length of hospital stay in the path group was 27.1 +/- 5.9 days and decreased 8.3 days in comparison with the control(p < 0.001). The cost of the path group was 145.290 +/- 23.773 points and 19.278 points less than the control(p < 0.005). In the path group the operation case per bed was increased 30% and the cost per bed was also increased 15% more than the control. CONCLUSIONS: The implementation of the clinical pathway decreased the length and the cost of hospital stay. The clinical pathway is effective to use the hospital resources, such as bed.

Costs and Cost Analysis↗