Biomedical subjects

Harushi Osugi

Publications and source records attributed to Harushi Osugi.

At least 37 records · Page 2Linked to original sources

PubMed2004

[Choice of chemotherapeutic drugs for colorectal cancers by DPD and OPRT activities in cancer tissues].

5-FU is the most widely used anticancer drug for digestive system cancers, and it has been recently reported that the effect of 5-FU varies with the amount of enzymes that are involved in the drug metabolism in the cancer tissue. In this report, we measured DPD and OPRT activities in the normal mucosa and colorectal cancer tissues and compared them with clinicopathological factors to examine the choice of chemotherapy for colorectal cancers. Forty-six patients with colorectal carcinoma (28 colon and 18 rectal cancers), which were resected in our department from 1999 to March 2003, were examined. There was no significant difference in the DPD activities between the normal and cancer tissues, whereas OPRT showed significantly higher activity in the cancer tissues. Although we did not find a relation between the DPD activity and clinicopathological factors, the OPRT activity showed a significant difference between gender and classification of tumor, and mucinous adenocarcinoma showed significantly lower OPRT activity than differentiated adenocarcinoma. The DPD activity of mucinous adenocarcinoma is related to catabolism of 5-FU is equal to that of adenocarcinoma, however, the OPRT activity is related to a main pathway of 5-FU phosphorylation is significantly lower. Thus, mucinous adenocarcinoma of the colon was more resistant to 5-FU than the differentiated adenocarcinoma. Therefore, for chemotherapy of mucinous adenocarcinoma, anticancer agents other than 5-FU should be selected.

Aged↗

PubMed2004

[A case of advanced descending colon cancer with peritoneal dissemination responding to weekly high-dose l-leucovorin/5-fluorouracil combination therapy].

We report a case in which l-leucovorin/5-fluorouracil (l-LV/5-FU) combination therapy was remarkably effective for non-resectable advanced descending colon cancer with carcinomatous peritonitis. A 65-year-old man complained of severe abdominal distension, abdominal pain and pulmonary failure, and was diagnosed as having ileus due to descending colon cancer. The patient underwent urgent open laparotomy to release the ileus condition on March 5, 2002. During the laparotomy, we established a diagnosis of nonresectable descending colon cancer accompanied by severe peritoneal dissemination and therefore performed only double-barreled transverse colostomy. The postoperative course was very good. Pathological examination of omental dissemination demonstrated moderately differentiated adenocarcinoma and cytology of ascites was class II. The levels of serum CEA and CA19-9 were within the normal ranges. l-LV/5-FU therapy was initiated postoperatively. Seven cycles of this chemotherapy regimen was performed with no apparent side effect during the treatment. There was no postoperative accumulation of carcinomatous ascites. The patient gained 15 kg compared with body weight admission. On abdominal computed tomography (CT), the primary lesion of the colon decreased 98% and there was no ascites found. To date, there has not been any sign of recurrence during the 19 months of follow-up after this therapy, and we are currently discussing closure of the transverse colostomy. This therapy may be useful for patients with advanced colon cancer accompanied by peritoneal dissemination.

Adenocarcinoma↗

PubMed2004

[A resected case of thoracic esophageal cancer in which pCR was obtained using low-dose of nedaplatin (CDGP)/5-FU and radiotherapy].

This is a report of a case with esophageal cancer in which pathological CR was obtained by neoadjvant chemoradiotherapy using a low-dose of nedaplatin (CDGP)/5-FU. The patient was a male aged 76. A protuberant lesion diagnosed as esophageal cancer was found in the middle thoracic esophagus by esophagography. Since another lesion in the upper thoracic esophagus was revealed by endoscopy, metastasis to the cervical lymph nodes was diagnosed by ultrasonography, and preoperative chemoradiotherapy combining a low dose of CDGP/5-FU with radiotherapy was performed. As side effects of this treatment, grade 2 stomatitis and granulocytopenia were observed. The main lesion of the esophagus was found to have significantly diminished through endoscopy after completion of the treatment, and with no malignant cells obtained by biopsy. No cervical lymph nodes were found. It was diagnosed as partial response (PR) through imaging diagnosis. Radical resection of esophageal cancer under right thoracotomy and laparotomy was performed. Operative findings were Ch x R-T3N0M0 Stage II R0 D2 Cur A. Pathological examination of resected specimens revealed no viable cancer cells in the esophagus or metastasis to the dissected lymph nodes. Neoadjuvant chemoradiotherapy using a low-dose of CDGP/5-FU is an effective treatment for esophageal cancer.

Aged↗

PubMed2004

[A case of recurrent stomach cancer treated with 5-fluorouracil responding to weekly paclitaxel therapy].

We report a patient with unresectable stage IV stomach cancer with metastasis to the paraaortic lymph nodes who achieved an effective response to neoajuvant chemotherapy, which allowed curability-B resection, and in whom weekly paclitaxel (TXL) therapy for postoperative recurrence was very effective in improving QOL. The patient was a 65-year-old man. After preoperative PMFE therapy, CEA decreased from 68.1 ng/ml to 0.8 ng/ml, and CA19-9 from 15,000 U/ml to 190 U/ml. The paraaortic lymph nodes disappeared, and stomach wall thickening decreased. The overall response to treatment was evaluated as a partial response (PR). After surgery, the patient was given TS-1, but became unable to take oral medication because of retroperitoneal and lymph node recurrence. Since the cancer appeared to be resistant to 5-fluorouracil (5-FU), the patient was treated by weekly TXL therapy. Increased appetite and weight gain were observed from the middle of the first course of therapy, and CEA decreased from 28.2 ng/ml to 4.9 ng/ml, and CA19-9 from 15,000 U/ml to 2,000 U/ml. Abdominal CT scans demonstrated shrinkage of the tumor. Although the patient died 1 year and 8 months after the initial examination, he was able to take oral medication and maintain good QOL for 10 months after the start of TXL therapy. Only grade 1 side effects (alopecia and leukopenia) were observed throughout the course. These results suggest that TXL therapy is effective also for 5-FU-resistant stomach cancer, and exhibits effects early even in patients in a poor general condition, causing only mild side effects, with early improvements in QOL.

Aged↗

PubMed2004

Suppressive effect of CPT-11 on rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine.

Irinotecan hydrochloride (CPT-11) is a potent anti-cancer drug with suppressive effects against gastric and colorectal cancers. However, no evaluation of CPT-11 for esophageal squamous cell carcinoma has been performed in vivo. In this study, we examined the tumor suppressive effects of CPT-11 on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. One hundred and fourteen rats were divided into six groups. Rats in groups 1-5 were treated with subcutaneous injection of NMBA at a dose of 0.5 mg/kg 3 times per week for 5 weeks. Rats in group 6 served as a control. Rats in groups 2 and 3 were treated with intragastric (i.g.) administration of CPT-11 at doses of 20 and 40 mg/kg, respectively, once a week simultaneously with NMBA-initiation up to the end of the experiment. Rats in groups 4 and 5 were treated with i.g. administration of CPT-11 at doses of 20 and 40 mg/kg, respectively, once a week after the NMBA-initiation period up to the end of the experiment. The incidence of papilloma and hyperplasia in the esophagus showed no difference between NMBA-treated groups. However, the multiplicity of hyperplasia was significantly reduced in all CPT-11 administration groups. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) was decreased on carcinogen-exposed squamous epithelium and preneoplastic lesions, although no significant differences were detected in the expression of single-strand DNA (ssDNA) and p53. These data suggest that CPT-11 has suppressive effects for esophageal tumors in the early step of the multistep process of carcinogenesis through antiproliferative mechanism.

Animals↗

PubMed2004

[Low-dose paclitaxel therapy as second-line chemotherapy for patients who previously received TS-1 therapy].

TS-1 is often used as first-line chemotherapy for treatment of advanced or recurrent gastric cancer, but there is no definite therapeutic policy for patients for whom TS-1 is not effective, or to whom it cannot be administered. We have treated 6 patients with low-dose weekly paclitaxel therapy as second-line chemotherapy after initial treatment with TS-1. These patients consisted of 3 males and 3 females with a mean age of 56 years. Four patients had recurrent gastric cancer and two had unresectable advanced gastric cancer. Paclitaxel was administered in doses of 80 or 100 mg weekly. Adverse events more severe than grade 3 were not observed, but there were 2 cases of leukopenia (grade 1) and 2 cases of decreased hemoglobin (grade 2). Mean survival time after the administration of paclitaxel was 139 days. Five patients died of their cancer, and one is still alive 382 days after the paclitaxel administration. The one-year survival rate after administration was 16.7%. Low-dose weekly paclitaxel therapy is therefore safe and effective for patients with advanced and recurrent gastric cancer who previously received TS-1 therapy.

Adult↗

PubMed2004

[A case of recurrent gastric cancer with skin and lung metastasis treated by low-dose paclitaxel therapy].

A case of recurrent gastric cancer with metastases to the skin and lung was treated successfully with low-dose paclitaxel after oral TS-1 administration. The patient was a 73-year-old man who underwent total gastrectomy for gastric cancer on April 3, 2000. Two years and four months after the operation, an increasing CA19-9 concentration and metastases to the skin and both lungs were observed. Oral TS-1 was given, but had to be stopped because of diarrhea. The metastatic lesions of the skin were resected, and low-dose paclitaxel (100 mg) was given once a week for 6 weeks. Five months later, the metastatic lesions of the right and left lung had decreased in size by 62% and 100%, respectively. CA19-9 fell to below the cut-off value 2 months after starting therapy. A decrease in the hemoglobin level of grade 1 was observed. Low-dose paclitaxel for recurrent gastric cancer after TS-1 therapy causes few side effects and may well be effective.

Adenocarcinoma↗

PubMed2003

High susceptibility of p53 knockout mice to esophageal and urinary bladder carcinogenesis induced by N, N-dibutylnitrosamine.

In human cancer, alterations in the p53 tumor suppressor gene are the most common genetic alterations. The aim of the present study was to detect sensitivity of the p53 (+/-) mice and their littermates p53 (+/+) mice to N, N-dibutylnitrosamine (DBN) carcinogenicity. In experiment 1, 6-7-week-old p53 (+/-) and p53 (+/+) mice were treated with 0, 0.025 and 0.05% DBN, respectively, in drinking water for 20 weeks. Esophageal squamous cell and urinary bladder transitional cell carcinomas (TCCs) and fibrosarcomas were found to be significantly increased in p53 (+/-) mice treated with doses of DBN compared to p53 (+/+) mice administered similar doses. In experiment 2, 6-7-week-old p53 (+/-) and p53 (+/+) mice were administered 0 or 0.05 % DBN in drinking water for 8 weeks. Immunohistochemical staining revealed a significant increase in numbers of p53 and bromodeoxyuridine (BrdU) positive cells in the esophageal and urinary bladder epithelia of DBN-treated p53 (+/-) mice compared to p53 (+/+) mice administered DBN. Molecular analysis revealed point mutations in the residual p53 allele in four of eight (50%) esophageal mucosa of DBN-treated p53 (+/-) mice, and in three of eight (38%) of treated p53 (+/+) mice. The results show that p53 (+/-) mice were sensitive to DBN treatment with respect to esophageal and bladder tumor development, with a mechanism that could be confined to early mutations of the residual p53 allele and increased cellular proliferation in the target organs.

Alleles↗

PubMed2003

Bronchoscopic ultrasonography for staging supracarinal esophageal squamous cell carcinoma: impact on outcome.

The precise, accurate diagnosis of malignant airway invasion is essential to determine the likelihood of complete resection and survival of patients with invasive carcinoma of the upper esophagus. The usefulness of ultrasonic scanning of the tracheobronchial wall by bronchoscopic ultrasonography (BUS) was studied, and results were compared with those of computed tomography (CT). Sixty-six consecutive patients with advanced squamous cell carcinoma of the upper esophagus treated from 1997 to 2000 were studied. The presence of tracheobronchial invasion was diagnosed by BUS based on an interruption in the most external hyperechoic layer of the tracheobronchus (corresponding to its adventitia). BUS was completed without any complication in all patients. The accuracy of diagnosis was validated intraoperatively, and it was better for BUS (90%) than for CT (62%) ( p = 0.001). Of the 26 patients diagnosed as being invasion-free by BUS, only 2 had invasion, compared to 7 of 22 patients who had invasion after CT scans had suggested they did not. Survival was worse for patients diagnosed as having invasion than not having it based on CT scans ( p = 0.0071), but the difference was more significant with BUS ( p < 0.0001). BUS is a safe, reliable staging modality for cancer in the upper esophagus. When surgery is considered, BUS is essential for determining whether a curative resection is possible.

Aged↗

PubMed2003

Quantitative determinations of duodenogastric reflux, prevalence of Helicobacter pylori infection, and concentrations of interleukin-8.

Billroth I or II reconstruction after distal gastrectomy often is associated with inflammation in the gastric remnant. We sought to determine which reconstructive procedure was most effective in preventing such remnant gastritis. Patients undergoing curative distal gastrectomy for cancer ( n = 82) were classified as group A (Roux-en- Y, n = 22); group B (Billroth I, n = 40); or group C (Billroth II, n = 20). Interleukin (IL)-8 concentrations in gastric mucosa were measured 3 months after surgery. In the absence of Helicobacter pylori infection, IL-8 concentrations were 13, 56, and 87 pg/mg protein in groups A, B, and C, respectively ( p < 0.05). In the presence of H. pylori infection, IL-8 concentrations were 61, 161, and 234 pg/mg protein in groups A, B, and C ( p < 0.01). Roux-en- Y reconstruction is better able to prevent remnant gastritis than either the Billroth I or II procedure as judged from IL-8 concentrations in gastric remnant mucosa.

Adult↗

PubMed2003

Esophageal tuberculosis presenting with an appearance similar to that of carcinoma of the esophagus.

A case of esophageal tuberculosis presenting with an appearance similar to that of esophageal cancer is reported. The patient was an 82-year-old man with progressive dysphagia. Barium swallow and esophagoscopy revealed an elevated lesion with deep ulceration in the middle thoracic esophagus. Esophageal carcinoma, in particular, an undermining type of undifferentiated carcinoma, was suspected fluoroscopically and endoscopically. Histological examination of biopsy specimens revealed no malignancy, but there were epithelioid granulomas and a few Langhans' type multinucleated giant cells. Endoscopic ultrasonography clearly demonstrated an extramural lesion with calcification and direct infiltration of enlarged subcarinal lymph nodes into the esophageal wall. Ultrasonographic and histological findings indicated the possibility of esophageal tuberculosis. Although no bacteriological evidence was obtained, a therapeutic trial for tuberculosis, using antituberculous drugs, was started. After 2 weeks, the enlarged subcarinal lymph nodes were markedly reduced in size. The patient's symptoms improved gradually and had disappeared 8 weeks after he started treatment, when tubercle bacilli were isolated from sputum. A connection between the esophageal wall and its adjacent structures was clearly demonstrated by endoscopic ultrasonography. For patients with findings indicative of esophageal tuberculosis on endoscopic ultrasonography, a therapeutic trial for tuberculosis should be considered, even if polymerase chain reaction assay or culture is negative.

Aged↗

PubMed2003

Refractory empyema caused by an intraoperative rib fracture sustained during esophagectomy: report of a case.

A 57-year-old woman underwent esophagectomy with three-field lymphadenectomy for lower esophageal cancer, followed by gastric roll reconstruction through the posterior mediastinum. A laparotomy and right thoracotomy with partial resection of the right fifth rib were performed. A purulent discharge requiring drainage developed postoperatively and continued for 3 months despite anastomotic integrity and the absence of a bronchopleural fistula. An empyema developed 3 months after drain removal, and a thoracostomy tube was reinserted. A displaced fragment of the right fifth rib was identified within the abscess cavity. Drainage and irrigation were not curative, and removal of the bone fragment was performed 18 months after the initial procedure. The patient has been symptom-free during 1 year of follow-up. We believe that the rib fragment functioned as a foreign body, which complicated treatment of the patient's postoperative infection.

Empyema↗

PubMed2003

Laparoscopic gastrectomy with regional lymph node dissection for upper gastric cancer.

Recently, a minimally invasive operation for gastric malignancies has been developed, and this laparoscopic operation is seen as a technique that will raise quality of life for patients. Previously, we reported this technique, as well as the results of a distal gastrectomy with regional lymph node dissection using hand-assisted laparoscopic surgery (HALS) for gastric cancer located in the middle or lower third of the stomach. This paper describes total or proximal gastrectomy with regional lymph node dissection by HALS on 28 cases of gastric cancer located in the upper portion of the stomach. After the mobilization of stomach and lymph node dissection via HALS, an anastomosis of the esophagus was performed intracorporeally with a conventional circular stapling device (PCEEA), whereas jejunojejunostomy and jejunogastrostomy were carried out extracorporeally with a conventional hand-sewn procedure through a HALS wound. The operation time and the amount of blood loss in all the patients were considered to be satisfactory, and the average number of dissected lymph nodes per patient was similar to that in open surgery. The patients had minimal morbidity and quick recovery after their operation. This technique was thought to be not only less invasive, but also similarly curative compared with open gastrectomy.

Adenocarcinoma, Papillary↗

PubMed2003

[A case of Barrett's esophageal cancer showing good response to combined chemotherapy with TS-1, CDDP and radiotherapy].

The patient was a 69-year-old man who, during a routine health examination, was found to have irregular mucosa in the lower esophagus, which was subsequently diagnosed by endoscopy as Barrett's esophagus. Endoscopic ultrasonography led to the diagnosis of advanced esophageal cancer with a depth of invasion corresponding to T2. While surgery was indicated, it was not considered feasible because of pleural adhesions due to old tuberculosis. Therefore, chemotherapy with TS-1 at the dose of 80 mg/day (4-week therapy followed by a 2-week withdrawal period) and CDDP at the dose of 3 mg/day (4-week of 5-day therapy followed by a 2-day withdrawal period) was instituted, followed 3 weeks later by the addition of radiotherapy with 1.8 Gy/day (5 times/week). Follow-up endoscopy revealed evident reduction in the lesion size 73 days after the start of TS-1 therapy, and complete disappearance of the lesion 185 days after the start of therapy. Grade 1 leukopenia was the only adverse effect of TS-1 noted in the patient. Treatment of Barrett's esophageal cancer is often conducted in accordance with the principles of treatment of esophageal squamous cell carcinoma, and surgical resection represents the most effective treatment. On the other hand, there have been no reports of effective adjuvant therapy. Based on our experience, the therapeutic strategy employed in this patient is considered to offer promise for the treatment of Barrett's esophageal cancer.

Aged↗

PubMed2003

[Remnant gastric cancer in which prolonged no change status was maintained with low-dose TS-1--a case report].

A no change (NC) status could be maintained in a patient with remnant gastric cancer for more than 500 days with low-dose TS-1. The patient was a 68-year-old woman who was found to have remnant gastric cancer during an endoscopic examination in follow-up on an outpatient basis after surgery for hepatocellular carcinoma in our department. Surgery was rejected as a treatment option because of severe liver dysfunction, and the patient was started on oral TS-1 80 mg/day. Both AST and ALT levels increased immediately after the start of TS-1, and TS-1 was discontinued until these levels improved. It was resumed at 50 mg/day, and there were no subsequent adverse reactions. Endoscopic examination on day 69 after the start of TS-1 showed that a partial response (PR) had not been achieved, but the lesion had shrunk. Endoscopy on day 454 after the start of TS-1 showed it had been possible to maintain a similar state. This was a rare case in which it was possible to achieve prolonged same status with low-dose TS-1.

Adenocarcinoma↗

PubMed2003

[Self-expandable metallic stent for unresectable malignant esophageal stricture].

Intraesophageal stenting using a self-expandable metallic stent is currently the first choice for patients with unresectable malignant stricture of the esophagus to improve their quality of life because of its efficacy and less invasiveness. Two types of stent are commercially available in Japan. The Ultraflex stent (Boston Scientific Co. Ltd.) is more flexible and less expandable than the Cook-Z stent (Wilson-Cook Co. Ltd.). Care should be taken based on the position of the stricture. Stenting in the cervical esophagus may cause discomfort. Stenting for a lesion adjacent to the airway may cause airway obstruction. Therefore airway stenting or provision for emergency intratracheal intubation is necessary. A stent with an antireflux mechanism would be effective in preventing gastroesophageal reflux following stenting at the esophagogastric junction. The development and legal approval of a stent with antireflux mechanism are expected. Some reported that anticancer treatment after stenting was effective, and some radiologists cautioned against the risk of radiation after stenting. The safety and efficacy of anticancer treatment after stenting remain to be clarified.

Esophageal Neoplasms↗

PubMed2003

[Resection of esophageal cancer infiltrating the left main bronchus following complete response to preoperative radiochemotherapy--a case report].

We report a case of esophageal cancer infiltrating the left main bronchus in which radical esophagectomy with clear surgical margins could be performed after preoperative radiochemotherapy. The patient was a 57-year-old man, who was found to have esophageal squamous cell carcinoma of the middle thoracic esophagus during a work-up of dysphagia. Bronchoscopy revealed an elevated region protruding into the lumen of the left main bronchus. After radiochemotherapy (liniac irradiation + low-dose FP therapy), the esophageal and bronchial lesion became smaller. The case was evaluated as a clinically complete response. Bronchoscopic ultrasonography showed a clear boundary between the membranous portion of the trachea and the esophageal wall. Based on these findings, the lesion was considered resectable and radical surgery, including 3-field lymph node dissection, was performed. The resected esophageal specimen had residual cancer cells in the muscularis propria covered with normal mucosa. However, the patient is currently healthy with no evidence of disease. The indication for surgical resection in cases of esophageal cancer with contiguous spread, and a good response to preoperative radiochemotherapy, is controversial. It is necessary to verify the effectiveness of surgical resection, as a secondary treatment, by accumulating data on cases such as the present one.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Reconstructive procedure after distal gastrectomy for gastric cancer that best prevents duodenogastroesophageal reflux.

Billroth I and II reconstructions are commonly performed after distal gastrectomy. Both may cause duodenogastric and duodenogastroesophageal reflux, conditions reported to have carcinogenetic potential. The aim of this study was to investigate which reconstructive procedure would most effectively prevent bile reflux into the gastric remnant and esophagus after distal gastrectomy. A group of 92 patients who underwent curative distal gastrectomy for gastric cancer were subjected and classified into three groups retrospectively by the reconstructive procedure undertaken: group A, Roux-en-Y (Roux-Y) reconstruction (n = 29); group B, Billroth I reconstruction (n = 41); group C, Billroth II reconstruction (n = 22). The bile reflux periods (percent time) for the gastric remnant and esophagus were measured with the Bilitec 2000 under standardized conditions. The percent time for the gastric remnant was significantly less in group A than in group B or C. In 61% of all patients, bile reflux into the esophagus was found to be more than 5.0% of the time; it was less in group A than in group B or C (p = 0.057). A questionnaire revealed a good correlation between the incidence of reflux symptoms and the percent time for the gastric remnant and esophagus. Roux-Y reconstruction is superior to either Billroth I or II reconstruction for preventing bile reflux into the gastric remnant and esophagus after distal gastrectomy.

Adult↗