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Biomedical subjects

Harushi Osugi

Publications and source records attributed to Harushi Osugi.

At least 55 records · Page 3Linked to original sources

Ambulatory intraesophageal bilirubin monitoring in Japanese patients with gastroesophageal reflux.

BACKGROUND: The role of reflux of duodenal contents in gastroesophageal reflux in Japanese patients, which may be different from that in Western patients, was studied. METHODS: Intraesophageal pH and the bilirubin concentration were monitored, using the Bilitec 2000, in 43 patients with reflux symptoms and 10 normal volunteers. The percentage of the time that spectrophotometric absorbance was 0.15 or more and pH was less than 4.0 was defined as the holding times (HTs) of bilirubin and acid, respectively. Severity of esophagitis was classified using the Savary-Miller (S-M) classification. RESULTS: Esophagitis was present in 37 patients; 5, 10, 13, and 9 patients had S-M grades 1, 2, 3, and 4, respectively. Both HTs in the volunteers were less than 5%. Bilirubin HT was more than 5% in 3 of the 6 patients without esophagitis, but the acid HT was less than 5% in these 6 patients. Acid HT was less than 5% in 4, 2, 2, and 2 patients with S-M grades 1, 2, 3, and 4, respectively. Bilirubin HT was less than 5% in 1 patient with S-M grade 2 esophagitis. Bilirubin HT in patients with S-M grades 3 and 4 esophagitis (50.9 +/- 5.8%) was higher than that in grades 1 and 2 (14.9 +/- 2.9%) (P < 0.0001), but this was not so for acid HT. In 32 patients, bilirubin HT exceeded acid HT. Bilirubin HT did not correlate with acid HT. CONCLUSIONS: Duodenogastroesophageal reflux occurred independently of and exceeded acid reflux. The amount of duodenogastroesophageal reflux correlated with the severity of esophagitis.

Adult↗

Different genetic alterations in rat forestomach tumors induced by genotoxic and non-genotoxic carcinogens.

Human beings are exposed to a multitude of carcinogens in their environment, and most cancers are considered to be chemically induced. Here we examined differences in genetic alterations in rat forestomach tumors induced by repeated exposure to a genotoxic carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methylnitrosourethane (MNUR), and chronic treatment with a non-genotoxic carcinogen, butylated hydroxyanisole (BHA) or caffeic acid (CA). A total of 132, 6-week-old male F344 rats were employed. Forty rats were treated with MNNG by intragastric administration at a dose of 20 mg/kg body wt once a week for 32 weeks, and 20 rats received 20 p.p.m. MNUR in their drinking water for 48 weeks. Further groups of 20 animals were administered 2% BHA or 2% CA in the diet for 104 weeks. The remaining rats were maintained without any supplement as controls. Multiple forestomach tumors were observed in all rats of the MNNG-, MNUR-, BHA- and CA-treated groups. Histopathologically, MNUR- and CA-treated groups showed almost the same pattern. On polymerase chain reaction-single strand conformation polymorphism analysis, H-ras and p53 gene mutations were observed at high and relatively low frequencies, respectively, in forestomach tumors induced by MNNG and MNUR. Most H-ras gene mutations were G-->A transitions in codons 7 and 12 of exon 1. On the other hand, forestomach tumors due to the non-genotoxic carcinogens, BHA and CA, had almost no mutations of the H-ras and p53 genes. Moreover, relative overexpression of cyclin D1 and p53 was detected in forestomach tumors induced by the genotoxic carcinogens, while their non-genotoxic counterparts had a tendency to show low expression of those molecules. Mutations of the beta-catenin gene were not detected in any group. The present study demonstrates that rat forestomach tumors induced by genotoxic and non-genotoxic carcinogens have different underlying genetic alterations, even if their pathological features are similar.

Animals↗

Bronchoscopic ultrasonography in the diagnosis of tracheobronchial invasion of esophageal cancer.

OBJECTIVE: To study the usefulness of bronchoscopic ultrasonography in diagnosing tracheobronchial invasion of esophageal cancer and to compare it with endoscopic ultrasonography, bronchoscopy, and computed tomography. METHODS: We prospectively investigated 59 patients with newly diagnosed esophageal cancer located at or above the level of the tracheal bifurcation. A 20-MHz ultrasonic probe covered by a sheath with a balloon inflated with water was used for bronchoscopic ultrasonography. The presence of tracheobronchial invasion was diagnosed on the basis of an interruption in the most external hyperechoic layer of the tracheal bronchus. RESULTS: Bronchoscopic ultrasonography was completed without complications in all patients, but endoscopic ultrasonography was performed completely in only 44% of them. The overall accuracy rates for diagnosis of tracheobronchial invasion on the basis of bronchoscopy, bronchoscopic ultrasonography, endoscopic ultrasonography, and computed tomography were 78%, 91%, 85%, and 58%, respectively. Statistical examination showed that the accuracy of bronchoscopic ultrasonography and bronchoscopy was significantly greater than that of computed tomography, and the accuracy of bronchoscopic ultrasonography was greater than that of bronchoscopy. CONCLUSIONS: Bronchoscopic ultrasonography is useful for evaluating cancer invasion into the tracheal bronchus. It is more accurate than the other methods and could be used to visualize the layered structure of the tracheal bronchus in all patients.

Aged↗

[A case of gastric cancer in the stomach wall used for mediastinal reconstruction after esophagectomy in which surgery was abandoned due to advanced age and complications but TS-1 was useful].

The patient was a 78-year-old man. Gastric cancer, type 3, was diagnosed by endoscopy in the subtotal stomach used for posterior mediastinal reconstruction after resection of thoracic esophageal cancer. Surgery was not considered to be feasible in this case because of cerebral infarction and decreased pulmonary functions; instead, the patient received TS-1 chemotherapy. Drug administration was started at the dose of 100 mg/day, one level lower than the standard dose of TS-1. Reduction in tumor size was noted endoscopically during the first course of treatment. At the end of the 4th course of treatment, the ulcerous lesion was found to have disappeared almost completely, and only mild mural irregularity was noted. The incidence of gastric cancer in the stomach tissue used for mediastinal reconstruction after esophagectomy has been reported to be 0.8%. In many of these cases, the cancer is already advanced at the time of diagnosis, precluding surgical resection. In this situation, chemotherapy with TS-1 is expected to be an effective method of treatment that can be administered at home in elderly patients with a variety of complications.

Aged↗

[Thoracoscopic esophagectomy].

The current roles of thoracoscopic esophagectomy in the treatment of cancer in Japan are described. Lymphadenectomy of the same quality as open surgery should be performed thoracoscopically to obtain good oncological outcomes. The indications for thoracoscopic esophagectomy are 1) no extensive pleural adhesions; 2) pulmonary function sufficient for single-lung ventilation; and 3) tumor not invading other organs. Hand-assisted or mini-thoracotomy facilitates the dissection of lymph nodes, especially on the left side of the trachea. However, for any type of procedure, a good en-face view is essential for safe and accurate lymphadenectomy. The magnifying effect of video, with the camera in close proximity, is important to maintain a proper dissecting plane. Although sufficient experience is necessary to master the learning curve, lymphadenectomy of the same quality as open surgery can be performed with mini-thoracotomy in a feasible time period. Thoracoscopic esophagectomy contributes to reducing postoperative pain and constrictive pulmonary dysfunction. It may be too soon to assert that the thoracoscopic approach can provide oncological outcomes comparable to those after open surgery because long-term follow up is not yet sufficient. Thoracoscopic esophagectomy, however, has the potential to improve the postoperative quality of life of patients with esophageal cancer.

Esophageal Neoplasms↗

p53 null mutations detected by a p53 yeast functional assay predict a poor outcome in young esophageal carcinoma patients.

Esophageal carcinoma is one of the most common gastrointestinal malignant neoplasms in the world. Recent advances in treatment modalities as well as surgical resection techniques have improved the changes of survival of patients with esophageal carcinoma, although the prognosis is worse than for the other gastrointestinal carcinomas. A more precise stratification beyond clinicopathological classification may help determine optimal treatment. The importance of p53 gene mutations in the pathogenesis of human esophageal carcinoma is well established, but it is still controversial whether the presence of p53 mutations adversely affects individual patient prognosis. In this study, we investigated the p53 mutations of esophageal carcinomas and their correlation with clinicopathologic factors. We employed a p53 yeast functional assay because it is highly sensitive and can detect mutations based on the actual function of the p53 gene, clarifying more precisely the role of this gene in esophageal carcinomas. We also studied young patients (< or =65 years old), because our previous study raised the possibility of differences in the importances in esophageal carcinogenesis in young and old patients. Of 43 young esophageal carcinoma patients (42 squamous cell and 1 undifferentiated carcinoma), 38 (88.4%) harbored p53 mutations. Twenty-seven missense and 11 null mutations were detected, but the presence of p53 mutations did not correlate with any clinicopathologic factor. However, the null mutation was a significant indicator of a poor outcome (P=0.0278). All except one patient who harbored null mutation died within 3 years after a macroscopically curative resection. These data suggest that the type of p53 gene mutation may be predictive of outcome in young esophageal carcinoma patients. Furthermore, null mutations causing loss of function of the gene product may play a more important role than missense mutations in tumor progression.

Aged↗

Percutaneous management of bile duct injuries after cholecystectomy.

Intraoperative biliary tract injuries are relatively uncommon, but are a cause of significant morbidity and mortality. We have repaired open biliary tract injuries found postoperatively in three patients without reoperation by percutaneous intervention. In two cases, biliary stents were placed percutaneously across the injured portion of the bile duct. For this procedure, a unique coaxial guidewire technique was used. The bile leaks resolved soon after insertion of the biliary stents. In one patient, an expandable metallic biliary endoprosthesis was inserted, and the temporary stent was removed. This patient had no signs or symptoms of cholangitis or biliary obstruction at the 6-year follow-up. The other patient died of heart failure soon after reconstruction. In the last patient, a biliary drain was inserted through the injured duct via the biliocutaneous fistula. In this case, biliary drainage alone resulted in resolution of the bile leak, because the injury was partial without a stricture. This patient was well at the 3-year follow-up. Percutaneous management of bile duct injuries is an alternative in selected patients.

Aged↗

Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with peritoneal dissemination.

The survival of gastric cancer patients with peritoneal dissemination is dismal and surgical intervention is rarely indicated. The usefulness of TS-1, a novel oral anticancer drug, composed of tegafur, gimestat and otastat potassium at a molar ratio of 1:0.4:1, and the role of surgical intervention for this condition was studied. Among gastric cancer patients with peritoneal dissemination, 18 treated during September 1999 to March 2001, and 16 before March 1999, were classified into the TS-1 group and control group, respectively, and survival was compared. TS-1 was administered orally twice daily, at a dose of 80 mg/m2/day, for 28 days followed by 14 days without treatment. This cycle was repeated. There was no difference in clinicopathologic factors, including surgical intervention, between the two groups. Eleven patients of the control group had chemotherapy using fluoropyrimidine. Grade 3-4 adverse reactions caused by TS-1 occurred in 1 patient. Survival was better in the TS-1 group than control group (p=0.0008), with median survival of 257 vs. 118 days. The median discharged period of patients of the TS-1 group with a performance status 0-2 on the Zubor scale was 211 days. TS-1 was effective to prolong the survival of gastric cancer patients with peritoneal dissemination. In this series of cases, surgical intervention to establish the route of oral administration was essential for this treatment.

Adenocarcinoma↗

Weak enhancing effects of simultaneous ethanol administration on chemically induced rat esophageal tumorigenesis.

Excessive alcohol consumption is associated epidemiologically with an elevated risk of esophageal cancer. In this study, we examined the effects of simultaneous administration of ethanol on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Groups 1-3 were treated with NMBA at a dose of 0.5 mg/kg body weight (high dose), and groups 4-6 received a dose of 0.1 mg/kg body weight (low dose), by s.c.-injection, 3 times per week for the first 5 weeks. Groups 1 and 4 were given ethanol free water as controls. Groups 2 and 5 were treated with 10% ethanol in their drinking water only at the time of NMBA treatment, while groups 3 and 6 were administrated the supplement continuously up to the end of the experiment. Macroscopically, with high dose NMBA-initiation, simultaneous 5-week and continuous 24-week ethanol administration demonstrated a tendency to increase the incidence and multiplicity of tumors, and also microscopically the multiplicity of papillary hyperplasias. In low dose groups, the incidence of esophageal papillary hyperplasias was significantly increased by continuous 24-week ethanol administration. Immunohistochemistry, proliferating cell nuclear antigen (PCNA) positive indices tended to be increased in tumors by simultaneous 5-week and continuous 24-week ethanol administration, but cyclin D1 expression was not affected. These data suggest that simultaneous ethanol administration have weak enhancing effects, and also promoting effects in post-initiation phase is present on NMBA-induced rat tumorigenesis.

Alcohol Drinking↗

Clinicopathologic and immunohistochemical features of surgically resected small cell carcinoma of the esophagus.

Esophageal small cell carcinoma (SmC) is considered an aggressive cancer carrying a poor prognosis, although the rarity of this tumor has impeded statistical evaluation. We reviewed records of 457 esophageal cancer patients treated in our department from 1986 to 2000, comparing clinicopathologic factors and post-treatment outcomes, for 9 patients with SmC, most undergoing esophagectomy including lymphadenectomy, with data from 128 patients with esophageal squamous cell carcinoma (SqC) invading to the muscular layer or beyond. Immunohistochemical features were compared between the SmC and 12 consecutive SqC. All patients studied had localized disease according to preoperative staging. SmC showed more ulcerative and infiltrative growth, and more aggressive lymphatic spread, than SqC. All SmC patients had lymph node metastasis (thoracic nodes, 9 patients: abdominal 6; cervical 1). All SmC specimens but no SqC were immunoreactive for neuron-specific enolase. Two and three SmC specimens were reactive for epithelial membrane antigen and keratin, respectively. Survival of SmC patients after esophagectomy (median, 11 months) was worse than for SqC patients (p=0.013). However, 1 SmC patient remains alive at 76 months. Survival was not related to any clinicopathologic or immunohistochemical features. While SmC shows aggressive behavior and worse outcomes than SqC, combining esophagectomy with chemotherapy or radiotherapy may prolong survival.

Aged↗

Prognostic factors in patients with squamous oesophageal cancer associated with solitary lymph node metastasis after oesophagectomy and extended lymphadenectomy.

It is not fully understood whether oesophageal cancer, associated with solitary lymph node metastasis, is still a local disease or already a systemic one. Among 283 patients with squamous oesophageal cancer who underwent oesophagectomy and 3-field lymphadenectomy, 37 patients had single metastasized nodes. Clinicopathologic factors, following Japanese Guideline for the Clinical and Pathological studies on Carcinoma of the Esophagus, related to survival and pre-operative predictability of nodal involvement was studied. Five-year survival was 48%. Initial pattern of recurrence was mostly haematogenous. Among the factors related to survival, grade of lymph node metastasis (pN1 vs. pN2, pN3, p=0.006) was more closely related than depth of invasion (pT1, pT2 vs. pT3, pT4, p=0.037). Five-year survival was 71.7% for pN1 patients, whereas it was 22% for pN2 or pN3 patients. Of the metastasized nodes 65% were <10 mm, and 27% was <5 mm in the maximum diameter. Oesophageal cancer is still a local disease in half of the patients with a solitary metastasized node. For these patients, dissection along the recurrent laryngeal nerve is necessary to retrieve the node possibly metastasized.

Aged↗

Causes of death and pattern of recurrence after esophagectomy and extended lymphadenectomy for squamous cell carcinoma of the thoracic esophagus.

Improved understanding of how esophageal cancer behaves following curative resection, including knowledge of other causes of death, is essential for informed decision making. The medical records of 246 consecutive patients with squamous cell carcinoma of the thoracic esophagus who had undergone esophagectomy and lymphadenectomy of the neck, chest, and abdomen that was deemed macroscopically curative, were reviewed. Patients who had had other malignancies or anticancer treatment were excluded. Median follow-up period was 1289 days (minimum, 730 days). The initial patterns of recurrence were classified as intramediastinal, hematogenous, or lymphatic. Forty-two patients died of a cause other than recurrence. The in-hospital death rate was 3.6%, and 19 patients died of pulmonary disease. Sixteen patients developed a second primary, most of which were in the upper aerodigestive tract; five of those patients died. Ninety-eight patients developed recurrence. Depth of invasion and number of nodal metastases predicted recurrence. The pattern of recurrence was intra-mediastinal, lymphatic, and hematogenous in 11, 21, and 67 patients, respectively. The patients with lymphatic recurrence survived longer than the patients with either of the other types of recurrences. Eighty-three percent of recurrences presented within 24 months. The time-to-recurrence correlated with survival after recurrence. The disease recurred earlier in patients with advanced stage than unadvanced disease at the time of esophagectomy. The time-to-recurrence, and anticancer therapy after the recurrence related to the survival. Meticulous care must be taken to detect hematogenous recurrence as early as possible so that adjuvant therapy may be started. Maintaining a good performance status permits the use of aggressive therapy should there be a recurrence. Pulmonary physiotherapy and treatment of metachronous primary tumors may improve overall survival.

Aged↗

The prognostic factors after radical esophagectomy for esophageal cancer with positive preoperative CEA.

BACKGROUND/AIMS: We investigated in this paper the clinicopathological factors that affect the prognosis of esophageal cancer with preoperative positive CEA. METHODOLOGY: Out of 252 patients with thoracic esophageal cancer who received curative resection in our department, we selected 33 cases with esophageal cancer that had positive serum CEA level preoperatively. We analyzed the clinicopathological factors which affect the prognosis in these CEA positive cases. RESULTS: There were no differences in preoperative CEA levels according to the variant clinicopathological factors. The number of lymph nodes metastasis, depth of tumor involvement, lymphatic invasion, and preoperative SCC antigen level were the significant factors influencing survival. But, only preoperative SCC antigen level was independent and a significant prognostic factor on multivariant analysis. CONCLUSIONS: While sensitivities of SCC antigen and CEA are low in esophageal cancer, the cases having positive value in both CEA and SCC antigen preoperatively have high recurrence rates after radical esophagectomy.

Aged↗

Surgical repair of esophagobronchial fistula caused by radiation injury.

We present an unusual case of a benign esophagobronchial fistula caused by radiotherapy to treat esophageal carcinoma which was closed successfully. A 62-year-old man with superficial squamous cell carcinoma of the esophagus underwent radiotherapy, including 60 Gy externally and 10 Gy intraluminally from January to March 1995. Esophagography revealed a fistula between the esophagus and left main stem bronchus on January 14, 1996. No residual cancer existed. Neither stenting with a silicone tube nor with a covered flexible metallic stent occluded the fistula. Thoracic esophagectomy, closure of the esophagobronchial fistula using a 2-cm nubbin of esophageal wall, surrounding the orifice of the fistula and antesternal gastric pull-through reconstruction with mediastinal lymphadenectomy were performed. The postoperative course was uneventful and there is no evidence of recurrence of the fistula or the cancer 5 years postoperatively. Radiotherapy may cause esophagobronchial fistula even in cases of superficial esophageal cancer. Bypass surgery should be considered because stenting is not effective for benign fistula without stricture.

Bronchial Fistula↗

Limitation of portal vein embolization for extension of hepatectomy indication in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Although percutaneous trans-hepatic portal vein embolization (PTPE) expands the candidate pool for hepatectomy in patients with hepatobiliary malignancies, the role of PTPE in patients with active hepatitis or cirrhosis has yet to be determined. METHODOLOGY: Records of patients who underwent PTPE of the right portal vein between 1984 and April 2001 were reviewed retrospectively. To determine the indication for PTPE and subsequent hepatectomy, clinical variables, including serum concentrations of hyaluronic acid (HA), procollagen type III peptide (P-III-P), and the 7S domain of type IV collagen (7S-IV), were compared between patients who underwent right hepatectomy (group A; n=44) and the other patients (group B; n=17). RESULTS: The scores for prediction of postoperative liver failure (prediction score) and serum HA and P-III-P concentrations were different in the two groups. Thirteen of 30 patients (43%) whose prediction score was more than 50, the limit of the hepatectomy without PTPE, successfully underwent right hepatectomy following PTPE. The resectability ratios increased to 75% and 100%, when the HA concentration was < or = 100mg/L and the P-III-P concentration < or = 0.7/mL. CONCLUSIONS: Serum HA and P-III-P concentrations are useful guidelines for identifying candidates for right hepatectomy following PTPE.

Aged↗

Correlation between duodenogastric reflux and remnant gastritis after distal gastrectomy.

BACKGROUND/AIMS: Many patients who undergo distal gastrectomy develop remnant gastritis. This report describes the correlation between remnant gastritis and the amount of duodenogastric reflux and looks at the relationship between Helicobacter pylori infection and duodenogastric reflux in remnant gastritis. METHODOLOGY: Sixty-two patients who underwent curative distal gastrectomy for gastric cancer with radical lymphadenectomy were studied. The period of bile reflux (percent time) into the gastric remnant was measured with the Bilitec 2000 under standardized conditions. Remnant gastritis was semi-quantified using the neutrophil infiltration score based on the updated Sydney System, and the presence of H. pylori infection was determined 12 weeks after the surgery. RESULTS: Overall, the correlation was not significant between the neutrophil infiltration score and the percent time (p=0.08). Similarly, the correlation was not significant in patients with H. pylori infection (p=0.30), but it was significant in patients without H. pylori infection (p=0.03). CONCLUSIONS: Duodenogastric reflux after distal gastrectomy can cause remnant gastritis in patients without H. pylori infection. Reconstruction with biliary diversion is protective against the development of remnant gastritis.

Adult↗

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy.

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.

Adult↗

Duodenogastric reflux eradicates Helicobacter pylori after distal gastrectomy.

BACKGROUND/AIMS: Patients who undergo distal gastrectomy often develop duodenogastric reflux and preoperative H. pylori infection is eradicated spontaneously after distal gastrectomy in some patients. However, whether a causal relationship exists has not yet been studied. This report examines the correlation between H. pylori eradication and the amount of duodenogastric reflux following distal gastrectomy. METHODOLOGY: Among 72 consecutive patients who underwent curative distal gastrectomy with radical lymphadenectomy for gastric cancer, 37 patients had H. pylori infection preoperatively and were included in this study. The period of bile reflux (percent time) into the gastric remnant was measured with the Bilitec 2000 under standardized conditions on the 14th day after the surgery. Endoscopic examination was performed to determine the presence of H. pylori infection on week 12 after surgery. RESULTS: The percent time was higher in patients whose H. pylori infection had been eradicated after distal gastrectomy (58.1+/-9.2%) than in patients who had H. pylori infection after distal gastrectomy (33.8+/-5.7%). CONCLUSIONS: Duodenogastric reflux correlates with spontaneous eradication of H. pylori infection following distal gastrectomy.

Adult↗