Biomedical subjects

T Kakegawa

Publications and source records attributed to T Kakegawa.

At least 37 records · Page 2Linked to original sources

PubMed1997

Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer.

A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II-IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients.

Adult↗

PubMed1997

A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study.

OBJECTIVE: To determine whether postoperative adjuvant chemotherapy confers a survival benefit on patients with esophageal squamous cell carcinoma undergoing radical surgery, we undertook a cooperative, prospective randomized controlled trial. METHODS: A total of 205 patients underwent transthoracic esophagectomy with lymphadenectomy at eleven institutions between December 1988 and July 1991. These patients were prospectively randomized into two groups (100 patients underwent surgery alone and 105 patients had additional two courses of combination chemotherapy with cisplatin (70 mg/m2) and vindesine (3 mg/m2). The two groups did not differ with respect to sex, age, location of tumor, and distributions of pT, pN, pM, or p stage. RESULTS: The 5-year survival was 44.9% in the surgery alone group and 48.1% in the surgery plus chemotherapy group. The relative risk was estimated to be 0.89 (95% confidence interval, 0.61 to 1.31) in the surgery plus chemotherapy group compared with the surgery alone group. No significant differences in survival were detected between the two groups, even with lymph node stratification. CONCLUSION: Postoperative adjuvant chemotherapy with cisplatin and vindesine has no additive effect on survival in patients with esophageal cancer compared with surgery alone.

Adult↗

PubMed1996

Postoperative chemotherapy for colorectal cancer by combining 5-fluorouracil infusion and 1-hexylcarbamoyl-5-fluorouracil administration after curative resection.

BACKGROUND: Colorectal cancer is one of the major malignant diseases and, recently, its incidence appears to be increasing. Surgical resectability is an important prognostic determinant; however, recurrent tumors are commonly noted, even after apparently curative surgery. Because such metastatic disease cannot be cured, better adjuvant therapies are urgently called for. METHODS: We studied the effect of postoperative chemotherapy using 5-fluorouracil (5-FU) infusions and 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration for curatively resected Stage II to IV colorectal cancer. This study was prospectively randomized and controlled and 251 (93.3%) of 269 patients were determined to be candidates for statistical assessment. The inductive regimen for Group A included a total of 6 5-FU intravenous injections, 10 mg/kg, on postoperative days 0, 1, 2, 7, 8, and 9. For maintenance therapy, Group A also received oral HCFU, 300 mg daily for 52 weeks beginning 2 weeks after surgery. The regimen for Group B included only 5-FU injections of Group A. RESULTS: There were no differences in the prognostic factors or doses of 5-FU between Groups A and B. In addition, no difference was observed in the toxicity rate between the two groups. Group A, with 5-FU infusions plus oral HCFU administration, produced a reduction in the recurrence rate and a prolongation of the survival time for patients with rectal cancer. In a retrospective analysis, this protocol was also effective for patients with Stage III to IV, wall invasion-positive, and lymph node metastasis-positive colorectal cancers. CONCLUSIONS: This study suggests that the combination of 5-FU infusions and the continuous oral administration of HCFU is a reasonable therapeutic approach for patients with surgically resected colorectal cancer and a high risk of recurrence.

Adult↗

PubMed1996

Comparative analysis of imaging modalities in the preoperative assessment of nodal metastasis in esophageal cancer.

Preoperative radiological findings of nodal status in 74 patients, using endoscopic ultrasonography (EUS), computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI), were compared to histopathology reports following transthoracic total esophagectomy with radical lymphadenectomy (TTE), involving complete dissection of the mediastinal and abdominal nodes and lower cervical lymph nodes. Accuracy, sensitivity, and specificity of each radiological investigation were calculated for each anatomic group of nodes. Statistical analysis revealed that EUS is more accurate and significantly more sensitive (P<0.01) for lymph nodes along the right recurrent laryngeal nerve and those in the upper and mid-periesophageal, infracarinal locations. Paratracheal and lower paraesophageal nodes are assessed better using CT whereas MRI is better for mid-paraesophageal and infra-aortic nodes. US is most accurate and sensitive for evaluation of cervical and abdominal nodes (P<0.01).

Abdomen↗

PubMed1996

Total pelvic exenteration for locally advanced colorectal carcinoma.

Twenty-six patients who underwent total pelvic exenteration for locally advanced colorectal cancer were studied retrospectively. The operative mortality rate was 8 per cent (two deaths). In patients with stage II primary disease the recurrence rate after curative surgery was three of seven, although the mean survival time was 58 months and the 5-year survival rate 71 per cent. Patients with stage III primary disease had a shorter mean survival time regardless of supposed curability (curative 14 months versus non-curative 9 months). Patients with stage IV disease had a mean survival time of 5 months. In patients who underwent curative surgery for recurrent disease the mean survival time was 33 months and 5-year survival rate 25 per cent, although in those receiving non-curative surgery the survival time was significantly shorter at 10 months (P < 0.05). Total pelvic exenteration is warranted for patients with stage II locally advanced colorectal carcinoma and is an option for those with recurrent carcinoma when performed with curvative intent.

Adenocarcinoma↗

PubMed1996

Effect of fentanyl citrate analgesia on glucose production following trauma in rats.

The postoperative hormonal milieu enhances glucose production. The objectives of this study were to determine whether fentanyl plus pentobarbital anesthesia reduced the excretion of stress hormones and whether this resulted in decreased glucose production following trauma. Male Sprague-Dawley rats were assigned into control and trauma. The trauma group was further subdivided into three groups according to the methods of anesthesia: T-1, pentobarbital (PB) alone; T-2, pentobarbital plus fentanyl (FE); and T-3, given PB during surgery and FE at the end of surgery. Glucose production was measured by a primed constant infusion of 3-3H-glucose. Fentanyl plus pentobarbital anesthesia prevented an increase in corticosterone levels in the plasma compared with in T-1 and T-3, 0.5 hr after the surgery. Fentanyl plus pentobarbital, anesthesia caused reductions of insulin and glucagon levels in the plasma and a decrease in catecholamines excretion in the urine. Glucose production was lower with FE+PB anesthesia than with PB alone (PB: 4.6 +/- 0.1 mg/kg/min vs PB+FE: 3.6 +/- 0.2 mg/kg/min, P < 0.05). However, fentanyl given at the end of surgery did not alter hormonal milieu and glucose production compared with pentobarbital alone. Blocking afferent neural stimuli from the wound and injury during the surgery is one approach to prevent an enhancement of postoperative glucose production.

Analgesia↗

PubMed1996

Effect of fentanyl citrate anesthesia on protein turnover in patients with esophagectomy.

The objectives of this study were to determine whether high doses of fentanyl anesthesia reduced the surgical stress level and to elucidate the effect of fentanyl anesthesia on protein turnover after esophagectomy. Seventeen male patients with esophageal cancer were divided into two groups, conventional anesthesia (CA) and fentanyl anesthesia (FA). The FA patients received 134.0 +/- 15.3 microg/kg fentanyl citrate and the CA patients 15.7 +/- 7.4 microg/kg fentanyl during the surgery. Protein turnover was measured by the method of bolus infusion of [15N]glycine (1 g). High dose of fentanyl anesthesia reduced cortisol levels during the surgery (CA 38.0 +/- 13.8 pg/ml vs FA 13.5 +/- 2.4, P < 0.05) and interleukin-6 levels in the plasma after the surgery (P < 0.02). The postoperative nitrogen retention was greater with fentanyl anesthesia than with conventional anesthesia. Both protein synthesis and breakdown rates were increased with fentanyl anesthesia, while they were unaltered in CA patients. Postoperative fibrinogen synthesis rate was greater with FA than with CA (CA 51.1 +/- 9.2%/day vs FA 100.9 +/- 14.0, P < 0.01). The protein turnover and fibrinogen synthesis data suggested a shorter duration of shock phase in FA patients than in CA patients. We concluded that a high dose of fentanyl anesthesia reduced surgical stress levels and shortened the postoperative shock phase, resulting in a nitrogen-sparing effect.

Acute-Phase Proteins↗

PubMed1996

Evaluation of the cell kinetics of MNNG-treated rat gastric mucosa based on AgNOR and ODC activity.

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features and cell kinetics in the gastric mucosa of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of gastric mucosa from both MNNG-treated and control rats were histologically examined by staining with nucleolar argylophilic nonhistone (AgNOR) proteins, and their ornithine decarboxylase (ODC) activity was determined every 2 months for 10 months. In 40% of the MNNG-treated rats, atrophy of the gastric mucosa was observed after 2 months, followed by adenomatous proliferation. More AgNOR-positive granules were found in the pyloric glands than in the fundic glands, and the total number of positive granules increased over time. Cancerous and hyperplastic lesions preferentially developed in the pyloric glands and showed significantly more AgNOR-positive granules than the normal mucosa. After 6 months the ODC activity in the MNNG-treated rats was significantly higher than that in the control rats. These results thus suggest that the pyloric glands have a high growth activity, while in addition, adenomatous proliferation is a characteristic pathological feature of precancerous lesions in the stomach in MNNG-treated rats.

Adenocarcinoma↗

PubMed1996

Effect of thyroidectomy on photoreceptor cells in adult rat retina.

To evaluate the effect of thyroid hormone on the retina in the adult male rat, morphometric and autoradiographic studies were made. Four days after an intravenous pulse injection of L-[3H]-leucine into adult male rats, the eyeballs were removed and the autoradiogram made. Two weeks after thyroidectomy, the length of photoreceptor cell inner segments was significantly decreased, but that of the outer segments did not change. Daily supplement of T4 (100 microg/kg sc twice for 2 days) before L-[3H]-leucine injection did not restore the decrease in the length. The silver grains of radioactive material distributed in the outer segment were divided into 3 equal portions. Thyroidectomy significantly increased the number of grains in the basal portion near the inner layer indicating a reduction in the renewal rate of the outer segment, but the T4 supplement did not restore the reduction in the renewal rate. These findings suggest that thyroid hormone is required to maintain the rate of renewal of the photoreceptor cell outer segment but the hormone supplement did not rapidly restore the renewal rate.

Animals↗

PubMed1996

Drug sensitivity testing for clinical samples from oesophageal cancer using adhesive tumour cell culture system.

A total of 83 specimens of surgically resected tumours from 78 patients with oesophageal cancer were assayed for drug sensitivity using an adhesive tumour cell culture system (LifeTrac CSA assay). Seventyone of 83 specimens had a sufficient number of cells to permit growth in culture and 57 of 71 (80%) were evaluable for drug response. Cells (3 x 10(3) ml-1 well-1) were cultured for 14 days and exposed to drugs on days 3-8. Growing cells were confirmed as cancer cells by immunohistochemical staining. IC90 values against several anti-cancer drugs were determined and population distributions of IC90 for each drug served as the basis for judging sensitivity. The 10th percentiles of IC90 (microgram ml-1) for CDDP, 5-FU, DOX, CPM, MTX, VP16, IFOS, VDS, BLM and CDDP + 5-FU were 0.3, 0.16, 0.005, 0.9, 0.006, 0.09, 0.8, 0.006, 0.04 and 0.15 + 0.09 respectively. The population distribution of IC90 against each drug showed a specific pattern that was very similar among histopathological gradings and stages of the disease. This system appeared to be a clinically applicable drug sensitivity test for human oesophageal cancer.

Antineoplastic Agents↗

PubMed1996

[Successful neoadjuvant chemotherapy in a patient with advanced gastric cancer with periaortic lymph node metastasis].

We described a case of advanced gastric cancer accompanied by metastasis to the periaortic lymph node. Two cycles of the neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. 5-FU (800mg/body/day) was administered as a continuous intravenous infusion for five days, and CDDP (10mg/body/day) was given as an intravenous infusion for an hour on days 1-5. The FP therapy resulted in a significant effect in the metastatic periaortic lymph node. Then, total gastrectomy with combined resection of spleen was done. Histological examination of the resected specimen revealed the histological effect showing Grade 3 in the primary site and Grade 2 in the periaortic lymph node. The patient is alive with no evidence of recurrence 13 months after operation. Thus, FP therapy is thought to be effective against advanced gastric cancer.

Aged↗

PubMed1996

[Treatment of superficial carcinoma of the esophagus--a review of responses to questionnaire on superficial carcinoma of the esophagus collected at the 49th conference of Japanese Society for Esophageal Diseases].

Histopathological characteristics and optimal treatment modality for superficial esophageal carcinoma were reevaluated by the way of nationwide questionnaires to the members of the Japanese Society for Esophageal Diseases. A questionnaire was designed for patients with preoperatively untreated superficial carcinoma of the esophagus who had undergone either surgical or endoscopic treatment between January 1, 1990 and December 30, 1994. As the results, the incidence of positive lymphatic invasion or lymphnode metastases tended to increase markedly as cancer infiltration reached the lamina muscularis mucosa. The majority of the cases with 0-I or 0-III components were sm. cancer. The indication of endoscopic mucosal resection (EMR) was limited to m1 and m2 superficial carcinoma in 76% of the institutions surveryed. Tumors measuring 2cm or more in diameter were resected piecemeal in 94% of the patients. The complications of EMR were observed in approximately 6.8% of patients, which denoted perforation, stenosis, and hemorrhage on most of the cases. As for the result of the treatment, almost all patients with m1 or m2 cancer survived. There was no significant difference in prognosis between m3 cancer and m1 or m2 cancer, but sm1 cancer showed worse prognosis than mucosal carcinoma. From this review, further study was advocated to refine the treatment strategy against m3 or sm1 cancer in the future.

Endoscopy↗

PubMed1995

Effect of methionine-deprived total parenteral nutrition on tumor protein turnover in rats.

BACKGROUND: Previous studies have shown that a methionine-lacking diet inhibited tumor growth in rats. The aim of this study was to determine how methionine free total parenteral nutrition (MTPN) can result in the inhibition of tumor growth on tumor protein metabolism in rats. METHODS: On day 0, AH109A rat ascites hepatoma cells were implanted subcutaneously into male Donryu rats (n = 68, body weight, 200-225 gm). On day 10, a catheter for total parenteral nutrition (TPN) was placed and either MTPN or standard TPN solution was given for 5 days. On day 15, 1-14C-leucine was infused continuously to measure tumor protein synthesis. Tumor proteolysis was calculated from tumor regional blood flow, using the 85Sr-microsphere injection method. RESULTS: 1) Tumor weight was reduced with MTPN. 2) MTPN did not affect tumor protein synthesis, probably because endogenous methionine production was increased with MTPN (87.3 +/- 13.5 mumole methionine/kg/hour vs. 218.6 +/- 29.5, P < 0.01); however, MTPN caused an increase of tumor proteolysis (2.68 +/- 0.53 mumole leucine/g/hour vs. 3.79 +/- 0.73, P < 0.05). CONCLUSION: The enhanced tumor protein breakdown contributed to the inhibition of tumor growth that was found with the rats given the methionine free diet.

Animals↗

PubMed1995

HLA A2601-restricted CTLs recognize a peptide antigen expressed on squamous cell carcinoma.

The CD4-CD8+ CTL (KE-4 CTL) cell line against autologous tumor cells was established in a patient with esophageal cancer. This KE-4 CTL recognized a peptide antigen on esophageal and lung squamous cell carcinomas in an HLA A2601-restricted manner, as evaluated by cytotoxicity against a panel of tumor cells, transfection experiments with HLA A2601 cDNA, and reconstitution with eluted peptides. None of the normal cells tested was lysed by this CTL. These results suggest the existence of HLA A2601-restricted CTL precursors recognizing a peptide antigen on SCC in a patient with esophageal cancer.

Antigens, Neoplasm↗

PubMed1995

Distal spread of rectal cancer and optimal distal margin of resection for sphincter-preserving surgery.

BACKGROUND: Ascertaining the optimal distal margin of resection in sphincter-preserving surgery has become an important problem. This study was designed to examine distal rectal spread of rectal carcinoma and to determine the optimal distal margin of resection for sphincter-preserving surgery. METHODS: Six hundred ten consecutive specimens of resected rectal carcinomas were analyzed retrospectively and pathologically. RESULTS: Sixty-one patients (10%) had distal spread. In patients who underwent curative surgery, distal spread was observed in only 3.8% (19/505). Distal spread was not found in patients with Stage I disease (0/150), according to the International Union Against Cancer stage. Only 1.2% (2/162) of patients with Stage II disease and 5.1% (10/195) with Stage III disease had slight spread but this was confined within a 1 cm length. Most patients with distal spread had a lower survival rate and died of distant metastasis rather than local recurrence, even after curative surgery. CONCLUSIONS: Distal spread seems to be an important risk factor for distant metastasis. Distal margin of resection of 1 cm may be appropriate clearance for most rectal cancers.

Female↗

PubMed1995

Surgical treatment for patients with pulmonary metastases after resection of primary colorectal carcinoma.

BACKGROUND: The optimum treatment for patients with pulmonary metastases from colorectal carcinoma is still controversial. METHODS: To evaluate the results of pulmonary resection in 22 patients with pulmonary metastases after resection of primary colorectal carcinoma, patients' characteristics were examined retrospectively. Eighteen patients had a solitary metastatic lesion and four had two lesions. RESULTS: Postthoracotomy recurrence occurred in 17 of the 22 patients (77.3%), and showed no correlation with the type of pulmonary resection. In 11 patients with a solitary lesion of less than 3.0 cm in greatest dimension, the 3- and 5-year postthoracotomy survival rates (PTSR) were 71.6% and 36.8%, respectively. Six of these patients received two or more thoracotomies for pulmonary recurrence. The 3-year PTSR for seven patients with a solitary lesion greater than or equal to 3.0 cm was 19.0%, and for the four patients with two lesions, 25.0%. A significant difference was noted in the survival rate according to both number and size of the metastatic lesions (P < 0.05). CONCLUSIONS: The number and size of metastatic lesions appear to be important prognostic determinants. Repeated thoracotomy can prolong survival for selected patients.

Adenocarcinoma↗

PubMed1995

Isolation and characterization of novel antimicrobial peptides, rugosins A, B and C, from the skin of the frog, Rana rugosa.

Three antimicrobial peptides were isolated from the skin of Rana rugosa. The major component, designated rugosin A, consisted of 33 amino acid residues and had structural homology (45%) with brevinin-2 of Rana porosa brevipoda. This peptide strongly inhibited the growth of gram-positive bacteria (e.g. Staphylococcus aureus 209P). The second peptide (rugosin B), a minor component, also had 33 amino acid residues, but was less homologous (33%) with brevinin-2. This peptide exhibited a striking antimicrobial activity against both gram-negative (e.g., Escherichia coli NIHJ) and gram-positive bacterial species. The third one, named rugosin C, composed of 37 amino acid residues, exhibited an antimicrobial activity against gram-positive bacteria. All three peptides had an intramolecular disulfide bond at the C-terminus.

Amino Acid Sequence↗

PubMed1995

Carcinomatous lymphatic permeation. Prognostic significance in patients with rectal carcinoma--a long term prospective study.

BACKGROUND: The question of whether lymphatic permeation in rectal carcinoma is an index of prognosis remains controversial. METHODS: A long term prospective study of lymphatic permeation of 288 rectal carcinomas was performed. The degree of lymphatic permeation was divided into four stages (Ly0 through Ly3). The median follow-up for the surviving patients was 84 months (range, 23 to 151 months). RESULTS: In patients with UICC Stage I or II disease, there was no correlation between the Ly0 and Ly1-3 groups' recurrence or survival rates. In patients with Stage IIIa disease, the rate of postoperative recurrence was significantly higher in the Ly1 or Ly2 + Ly3 groups compared with the Ly0 group. The 10-year survival and disease free survival rates in patients with Stage IIIa disease were both 90.0% in the Ly0 group, 63.6% and 62.5% in the Ly1 group, and 52.0% and 45.5% in the Ly2 + Ly3 groups, respectively. A significant difference was noted in the survival rates between the Ly0 and Ly2 + Ly3 groups (P < 0.05), and was noted in the disease free survival rates between the Ly0 and Ly1 (or Ly2 + Ly3) groups (P < 0.05, P < 0.005). In patients with Stage IIIb disease, there were trends toward higher recurrence, lower survival, or disease free survival rates in the Ly2 + Ly3 groups compared with the Ly1 group (P < 0.1). CONCLUSIONS: The degree of lymphatic permeation is an important prognostic factor in patients with Stage III disease, especially in those with Stage IIIa disease. It should be classified as a clinical subgroup.

Aged↗