[Clinical results of esophageal cancer in Kyushu District--analysis of 2,126 cases--the Study Group of Combined Therapy of Esophageal Carcinoma in Kyushu].
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Adult↗
Biomedical subjects
K Inokuchi
Publications and source records attributed to K Inokuchi.
Chromatin structure of the human dihydrofolate reductase gene promoter. Multiple protein-binding sites.
The chromatin structure of the promoter region of the human dihydrofolate reductase gene was determined using a variety of nucleases including DNase I, micrococcal nuclease, several restriction endonucleases, exonuclease III, and Bal31. Two separate regions from -670 to -340 (the distal hypersensitive region) and from -170 to +150 (the proximal hypersensitive region) were shown to be essentially free of proteins as indicated by their accessibility to both endo- and exonucleases. Within the proximal hypersensitive region, one protein appears to be bound at the start site for transcription. A 170-base pair fragment between the two hypersensitive regions was highly resistant to all nucleases tested. Multiple barriers against exonuclease digestion and resistance to dissociation by high salt concentrations suggest that more than one protein is tightly bound to this region. The upstream sequence from -670 and the downstream sequence from +150 were shown to be packaged into nucleosomes. The selective accessibility of certain sites to micrococcal nuclease cutting indicates that the initial nucleosomes are phased upstream from the distal hypersensitive region. There appears to be a protein bound between the phased nucleosomes and the upstream boundary of the distal hypersensitive region. These results suggest that the normal nucleosome array is interrupted by about 900 base pairs of nucleosome-free DNA to which several nuclear proteins bind in a DNA sequence-specific manner.
Chromatin↗
Prognostic factors of esophageal carcinoma: univariate and multivariate analyses.
The correlation of 5-year survival rate with various clinical and histopathological factors was studied using univariate and multiple analyses of 128 patients who had undergone resection for esophageal carcinoma between 1965 and 1978 in the Department of Surgery, Kyushu University Hospital. The depth of penetration, lymph node metastasis, lymphatic or vascular invasion, and INF had a significant correlation with 5-year survival in the univariate analysis; however, only depth of penetration and lymph node metastasis were prognostic factors with a significant difference, in the multivariate analysis. In 55 patients in whom the cell nuclear DNA content had been determined, the DNA pattern was the greatest prognostic factor (p less than 0.01), in multivariate analysis. We propose that the DNA distribution in the malignant cells should be examined as a most pertinent prognostic factor.
Adult↗
Superficial spreading esophageal cancer controlled by hyperthermo-chemo-radiotherapy: a case report.
Hyperthermo-chemo-radiotherapy (HCR) was prescribed for a patient with superficially spreading esophageal cancer, since severe lung dysfunction presented too great a surgical risk. Viable cancer cells completely disappeared after HCR and 8 months later, at this writing, the patient is living in good condition. Conservative treatment with HCR for patients with esophageal cancer is effective for carefully selected patients.
Aged↗
Histopathological evaluation of hyperthermo-chemo-radiotherapy for carcinoma of the esophagus.
The effectiveness of preoperative hyperthermo-chemo-radiotherapy for 25 patients with carcinoma of the esophagus was histopathologically compared with findings in 104 patients treated preoperatively with irradiation only. The preoperative hyperthermo-chemo-radiotherapy increased the rate of "markedly effective" in the resected tissue, when compared with findings in cases of irradiation only. With regard to long survival rates, the 5-year survival rates of patients classed as "markedly effective" with preoperative combined therapy exceeded events in patients classed as "moderately effective," and "ineffective," with statistical significance. Preoperative hyperthermo-chemo-radiotherapy is the recommended treatment for patients with carcinoma of the esophagus.
Aged↗
Hyperthermochemoradiotherapy and esophageal carcinoma.
Cancer of the esophagus still poses considerable treatment problems, with a poor 5-year survival rate after surgery, an even worse outlook after radiation and surgery, and a not very satisfactory response to chemotherapy. After several years of continued research, in 1983 we developed a Radio Frequency System with endotract electrode and thermosensors for administering hyperthermochemoradiotherapy to patients with carcinoma of the esophagus. Results in 129 patients are discussed. Immediate improvement of subjective complaints and decrease or elimination of the cancer lesion are so distinct that this treatment, by means of an endotract antenna, shows promise as a modality for esophageal lesions and may find application in diseases such as colorectal cancer or carcinoma of the uterine cervix.
Bleomycin↗
Preoperative detection of a highly malignant type of early gastric carcinoma by cytophotometric DNA analysis.
A cytophotometric DNA analysis was made of gastroendoscopically biopsied materials of 43 patients with early gastric carcinoma and the data were compared with the DNA patterns of the resected specimens of these patients. The DNA patterns could be classified into two types, Low Ploidy and High ploidy, according to the degree of dispersion of the DNA value. The Ploidy to Ploidy coincidence of the DNA patterns between biopsied material and the resected specimen in the same lesion was noted in 93 per cent (39/42). The DNA patterns of the resected specimens were consistent in the majority of cases, regardless of the areas examined, center or periphery, and mucosa or submucosa of the same lesion. This study provides evidence that a highly malignant type of early gastric carcinoma, Pen A type, could be differentiated in gastroendoscopically biopsied materials by a cytophotometric DNA analysis.
Biopsy↗
Postoperative adjuvant chemotherapy for gastric cancer, the second report. Analysis of data on 2873 patients followed for five years.
The effectiveness of combination chemotherapy with mitomycin-C (MMC) plus futraful (N1-(2'-tetrahydrofuryl)-5-fluorouracil), as an adjunct to surgery for gastric cancer was investigated in a prospective randomized controlled study. Three thousand and thirty-three Japanese patients in 344 hospitals were entered and 2873 could be followed for 5 years. All patients had undergone gastrectomy from April 1977 to May 1979 and were assigned, at random, to either Groups A, B or C. In Group A, bolus MMC was administered with no further treatment. In Group C, oral futraful was given for one year, without MMC induction. In Group B, both a bolus MMC injection and oral futraful were prescribed. This randomized study showed no statistical difference in the 5 year survival rate among the three groups. However, in patients given MMC and put on oral futraful for one year, the 5 year survival rate for those with stage III gastric cancer or for those with positive lymphnode metastasis plus obvious serosal invasion seemed to be improved.
Adult↗
Development of erosive gastritis in a canine model of esophageal varices.
We designed a reproducible canine model of esophageal varices, based on the concept of a regional hyperdynamic state in the upper stomach. Arterialization of the left gastric vein concomitant with the distal splenorenal shunt led to a stable hyperdynamic state and reproducible esophageal varices occurred. In the long-term follow-up of these dogs with varices, the erosive gastritis seen in the upper stomach clearly resembled clinically observed lesions. Hemodynamic and morphological studies revealed that gastric mucosa of these animals was in an ischemic state, even though there was a remarkable increase in blood flow in the submucosal area. It is suggested that the decrease in mucosal blood flow, as induced by the hyperdynamic state caused erosive gastritis.
Animals↗
Acute liver failure in rats inhibited by intrasplenic administration of OK-432.
Intrasplenic administration of OK-432, an immunostimulant derived from Streptococcus, prevented hepatic failure induced in rats by D-galactosamine. When OK-432 was given 1.0 K.E. (Group I) or 0.1 K.E. (Group II) into the subcutaneously transpositioned spleen three times prior to dosing with D-galactosamine, survival rates were 100 and 87%, respectively. On the contrary, with a splenic injection of saline (Group III), the survival rate was 47 and 32% in rats given OK-432 1.0 K.E. intraperitoneally (Group IV). The poisoned rats given no pretreatment (Group V) survived at a rate of 26%. These results show that intrasplenic administration of OK-432 leads to a significant enhancement of survival. Metabolic data and histological findings were compatible with survival rates, in each group. Activation of the reticuloendothelial function by the intrasplenic administration of this immunostimulant seems to have prevented acute liver failure.
Acute Disease↗
Combined effects of hyperthermia, bleomycin, and X rays on Ehrlich ascites tumor.
The combined effects of water-bath hyperthermia at 42.5 degrees C for 30 min, 1/10 LD50 Bleomycin iv, and 200 rad x irradiation were studied in DDD strain male mice with Ehrlich ascites tumor. The objective was to acquire data on the optimum regimen for a combined administration of these three modalities. The treatments were given 10 days after the inoculation of 2 X 10(6) of the cells into the right hind limb. Concomitant application of the three modalities led to an 80% regression. A single modality produced no significant effect and a 30-50% regression occurred when only two modalities were combined. To assess the influence of timing and sequence, hyperthermia was applied at 1, 2, 4, and 6 hr before, after, or simultaneously with the combination of Bleomycin and 200 rad X ray. A significant effect was obtained in the case of concomitant application of the three and hyperthermia was effective when applied within 2 hr before or after administration of Bleomycin plus irradiation. This enhancement disappeared at 4-hr intervals.
Animals↗
Mechanisms involved in acute lung edema induced in dogs by oleic acid.
We investigated mechanisms related to the development of acute lung edema, as induced by oleic acid in adult mongrel dogs. The intravenous injection of oleic acid (0.04 ml/kg) was considered to induce a permeability edema, as an enhancement of transvascular protein clearance was observed after the injection. The effects of oleic acid injection on systemic blood pressure (SBP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO) and airway pressure (AWP) were measured. A significant decrease in CO and increase in AWP were evident after the injection, but there were no changes in SBP, PAP and PAWP. Treatment of the animals with prostaglandin I2 (PGI2) did not alter the induction of edema by oleic acid. However, the decrease in CO and increase in AWP were normalized by treatment with PGI2. Blood platelet count was not affected by oleic acid given in a dose of 0.04 ml/kg. To determine the direct effect of oleic acid on the vascular endothelium, the agent was injected through a catheter placed in the pulmonary artery. Electron microscopic examination revealed severe vacuolation on the endothelium of the pulmonary artery after only 1 min of exposure to oleic acid. Increased permeation of Evans blue into the subendothelial tissue was also observed with oleic acid treatment, compared with findings in the controls. These results indicate that the lung edema induced by oleic acid is due to an increased protein clearance, probably through a direct toxic effect on the vascular endothelium rather than an indirect toxic effect of chemical mediators released from the aggregated platelets.
Airway Resistance↗
Renal allograft dysfunction with acute hemorrhagic cystitis caused by adenovirus in a recipient of a transplanted kidney.
We experienced acute hemorrhagic cystitis with renal dysfunction in a recipient of a transplanted kidney. This acute hemorrhagic cystitis was caused by adenovirus type 11. Either elevation of antibody titers or isolation in urine of adenovirus type 11 was identified in six cases out of 11 in seven reports which we collected. Graft dysfunctions were complicated on seven cases out of 11 in these seven reports. These graft dysfunctions have been considered as an acute rejection, but we suggest that they may be graft nephropathy caused by adenovirus type 11 infection.
Acute Disease↗
Continuous ambulatory peritoneal dialysis (CAPD) policy for renal transplantations in adults.
In Japan CAPD in cases of renal transplantation used to be feared because of CAPD peritonitis occurring under conditions of immunosuppression. We experienced two cases of CAPD with renal transplantation. Case 1 was a 27-year-old woman who underwent living related renal transplantation on March 7, 1986 after 4 months CAPD without CAPD peritonitis. In this patient the CAPD catheter was removed on the 17th POD with a good graft function. Case 2 was a 38-year-old woman who underwent living related renal transplantation on November 8, 1985. The graft deteriorated due to acute rejection and ALG allergy. On February 1, 1986 the graft was removed after insertion of a CAPD catheter. The patient began CAPD. Therefore, CAPD was found to be a safe procedure for renal transplantation. Our policy concerning CAPD for renal transplantation is as follows: A patient should not be transplanted for 1 month after successful treatment of an episode of peritonitis. After renal transplantation the catheter is removed on completion of the transplantation procedure in cases of two haploidentical living related transplants and electively 2-12 weeks after renal transplantation in cases of one haploidentical living related transplant or cadaveric transplants. The CAPD catheter is used again when there is temporary or permanent graft failure.
Adult↗
The quality of life is sustained after operation for carcinoma of the esophagus.
An interview was conducted to determine the quality of life, both objectively and subjectively, in 64 patients without a recurrence of the disease more than one year after esophageal resection and reconstruction with a gastric tube for carcinoma of the thoracic esophagus. Despite the decrease in body weight, the patients appeared to be well adjusted and had a most optimistic attitude toward their illness. The laboratory data showed normal values, postoperatively. As there was no evidence of a diminished quality of life in these patients, we consider that physicians should recommend surgical therapy for patients with carcinoma of the esophagus.
Aged↗
Intratumoral injection of thymidine: enhancement of the antitumor activity and incorporation of 5-fluorouracil into tumor RNA in a murine tumor system.
Intratumoral injection of thymidine (dThd) into mice bearing an Ehrlich ascites solid tumor in combination with an ip injection of 5-fluorouracil (FUra) was performed to investigate the following: (a) whether intratumoral injection of dThd would increase both the incorporation of FUra into tumor RNA and the antitumor activity of FUra as effectively as ip injection of dThd, and (b) whether intratumoral injection of dThd would have a selective advantage for increasing the incorporation of FUra into the tumor RNA, relative to normal tissue RNA. Pulse-labeling with [3H]FUra at different times after dThd injection indicated that the most effective incorporation of FUra into the tumor RNA occurred with both intratumoral and ip injection of dThd, when FUra and dThd were given simultaneously. The amount of FUra-containing RNA [(FU)RNA] was dThd dose-dependent and reached a maximum at a dThd dose of 100 mg/kg, in the case of either intratumoral or ip injection. The maximal level with intratumoral injection of dThd was twofold higher than the level with ip injection and at least fivefold higher than the level achieved with FUra alone. In a time course study, the amount of (FU)RNA formed after intratumoral injection of dThd was comparable to the level obtained with ip injection, which was fourfold to sixfold greater than that seen with FUra alone. Furthermore, in the four normal organs (bone marrow, intestine, kidneys, and lungs) the amount of (FU)RNA formed after intratumoral injection of dThd was markedly lower than the level with ip injection. Assay of FUra degradation products revealed low levels of FUra catabolism in the tumor tissue compared to liver. In addition, therapy experiments showed that the antitumor activity of FUra was increased 17-fold by coadministration of dThd by either route.
Animals↗
[Natural history of gastric carcinoma viewed from growth patterns of early carcinoma].
Regarding the natural history of gastric malignancy, we arrived at the following conclusions. There are at least two types of gastric cancers: a rapidly growing type (Pen) and a slow growing superficial type (Super). It seems that the Super type early cancer progresses to a funnel shaped, non-Borrmann advanced type of cancer of a lesser incidence, and the Pen type leads to the most advanced cancer of Borrmann type. A slow growing Super type cancer is more likely to be detected because it remains at the early stage for a longer period. Conversely, the rapidly growing Pen type cancer is less likely to be detected until it has reached an advanced stage. Ulcer symptoms accompanying the Super type seem to create a detection bias, and the chance of detection is increased. A rough estimation of the occurrence rate of slow and rapidly growing cancer is 1:2 or 1:3. Considerable effort should be directed to studies on rapidly growing gastric cancer, and the early detection of Pen type cancer is of top priority. The focus of our inspection future should be directed to differentiation of "type oriented early cancer".
Aged↗
[Secondary malignancies after gastrectomy for gastric cancer].
In patients who have undergone gastrectomy for gastric cancer, the use of adjuvant chemotherapy has now become very widespread in Japan. The possibility of secondary malignancies in these patients emerges as a long-term effect of these therapeutic agents. This collaborative study was done to examine the possibility of secondary malignancies resulting from both operative methods and anticancer agents at the surgical departments of seven major institutions in Japan. The study was carried out using questionnaires for all patients with gastric cancer who had undergone gastrectomy between 1960 and 1975 in those hospitals and who had survived more than one year after gastrectomy. A total of 235 secondary malignancies (2.32%) were noted among 10,138 gastrectomized patients, and 22 cancers of the gastric remnant (0.29%) were recorded among 7,672 subtotal gastrectomized cases. Cancers suspected to be recurrent gastric cancer were all excluded. As to anticancer agents, Mitomycin C (MMC), 5-Fluorouracil (5-FU) or Tegafur and Cyclophosphamide (EDX) were analyzed. The occurrence rate of secondary cancers in gastric cancer patients was calculated in many instances by dividing the actual number of secondary cancers by the total time at risk (person-years). Patients with gastric cancer who had undergone gastric resection revealed a lower incidence of secondary malignancies than had been expected. The most common secondary cancers were those occurring in the digestive system, followed by those of the respiratory system. With regard to MMC, 67 secondary cancers (2.21%) occurred in the MMC group and 168 cancers (2.36%) in the non-MMC group. Although the overall incidence of secondary cancers showed no difference between MMC and non-MMC groups, secondary cancers of the digestive system were less common in the MMC group than in the non-MMC group. A total of 22 cancers originated in the gastric remnant out of 7,672 subtotally resected stomachs. The interval between the first operation and cancer of the gastric remnant varied greatly without showing any detectable trend. Nine cancers were observed to involve the anastomotic site while 14 did not involve the anastomotic site. The incidence of cancer of the gastric remnant tended to be slightly higher with the Billroth II method than in the Billroth I method, but there was no difference in the site of secondary malignancy between the two groups.
Adult↗