[Autopsy case of esophago-bronchial fistula caused by primary lung cancer].
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Biomedical subjects
Publications and source records attributed to M Kodama.
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Early postoperative evaluation was prospectively performed in 35 gastric cancer patients after pylorus-preserving gastrectomy (PPG) between 1989 and 1991, comparing the results with those of 29 patients who underwent conventional distal gastrectomy (CDG). Surgical stress, including the duration of operation (149.0 +/- 4.3 minutes) and the total volume of bleeding at operation (97.0 +/- 11.2 g), was significantly less in the PPG patients. Early postoperative complications were seen in 31% after PPG and in 35% after CDG. The most frequent complication in PPG patients was remnant gastric stasis (23%). Endoscopy showed redness or erosion (or both) of the gastric remnant in 17% after PPG and in 81% after CDG. Bile regurgitation was demonstrated in 11% after PPG and in 62% after CDG. In PPG patients, the pyloric ring opened and closed during the examination. Gastric pH was 4.2 +/- 0.4 in PPG patients but was significantly lower in CDG patients. The resting gallbladder area, examined by ultrasonography, demonstrated no changes after PPG but was significantly enlarged after CDG (from 11.3 +/- 1.2 cm2 to 15.8 +/- 1.5 cm2 at 2 weeks). The percentage of the original resting gallbladder area at 20 minutes after injection of cerulein increased slightly in PPG patients but recovered thereafter, whereas in CDG patients it increased significantly (from 39.4 +/- 8.3% to 66.7 +/- 9.1% at 2 weeks). No gallstone formation was detected throughout the observation period after PPG, whereas after CDG it was detected in two patients at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)
Group I pepsinogen (PG-I) staining was performed in the gastric carcinoma tissues of 75 patients by the peroxidase-antiperoxidase (PAP) method, 44 cases (59%) of which were positive for PG-I, suggesting that they were PG-I-producing gastric carcinomas. Type IV gastric carcinoma by the Borrmann classification and/or poorly-differentiated adenocarcinoma were positive for PG-I in high incidence. Serum and urinary levels of PG-I were determined by the Pepsinogen I Radioimmunoassay Kit in patients with gastric carcinoma who underwent total gastrectomy. The levels of PG-I declined remarkably or disappeared at 1 week after curative surgery. Changes of serum PG-I levels after total gastrectomy were observed in 9 patients with PG-I-producing gastric carcinomas, 7 of whom died of recurrence. The PG-I values became elevated with recurrence in 5 of them and the values increased with the passage of time. In contrast, no substantial changes in PG-I levels occurred in patients with no recurrence. These results suggest that PG-I is useful for the early detection of recurrent disease after total gastrectomy in patients with PG-I-producing gastric carcinomas.
Both basic and clinical studies were undertaken to determine the indications for pylorus preserving gastrectomy for patients with early gastric cancer located in the middle third of the stomach. This procedure is different from conventional subtotal gastrectomy in that it retains a 1.5 cm length of the pyloric cuff and it neglects to dissect the suprapyloric lymph node, with the remaining pyloric branch of the vagal nerve being preserved. Therefore, it is essential that this limited operation be performed only in cases without metastasis to the suprapyloric lymph node. The distance from the caudal end of the tumor to the cut edge is far enough when the tumor is in the middle third of the stomach. The direction of lymph flow, as determined in 14 cases by activated carbon particles (CH-40), suggests that there is limited lymph flow towards the suprapyloric lymph node from the middle third of the stomach. Lymph node involvement was investigated in 154 patients with early gastric cancer located in the middle third of the stomach who had undergone conventional subtotal gastrectomy with regional lymph node dissection between 1976 and 1989. By analysis of the relationship between lymph node metastasis and the clinicopathologic findings revealed before operation, i.e. gross appearance, histological classification, and tumor size, the indications for pylorus preserving gastrectomy were determined as follows: (1) any case with tumors smaller than 2.0 cm in maximum length, and (2) cases with a tumor of 2.0 to 4.0 cm if it is a mucosal cancer, if it is located at the greater curvature, or if it is an elevated type IIa cancer. This operation has been performed on 11 patients to date without postoperative complaints or sequelae.
Epidemiological evidence suggests that smoking is a major cause of human lung cancer. However, the mechanism by which cigarette smoke induces the cancer remains obscure, although in tobacco carcinogenesis, promotion and/or co-carcinogenesis may have crucial roles. The epidemiological data show that if an individual stops smoking, the risk of his contracting lung cancer increases no further. Moreover, laboratory experiments show that cigarette smoke condensate (CSC) exhibits co-carcinogenic and promoting activities in tumour production and malignant transformation. Clastogenic action is thought to be intimately involved in tumour promotion, and it is therefore interesting that visible chromosome changes such as chromosome aberrations and sister chromatid exchanges are known to be caused by cigarette smoke. However, there has been no previous direct demonstration that cigarette smoke can cause single-strand breaks (SSB) in DNA. Here we report that cigarette smoke induces considerable numbers of DNA SSB in cultured human cells, and that such strand breaks may be ascribed to active oxygen generated from cigarette smoke.
Systemic sepsis is a frequent and fatal complication of postoperative patients. More recently, therapeutic trials of plasma or blood exchange are performed in septic patients for the purpose of reducing both endotoxins and albumin-bound toxins. As an alternate approach such as this for the removal of endotoxin directly from the blood, the authors recently developed polymyxin B immobilized fiber (PMX-F) as a biomaterial for selectively detoxifying endotoxin. That this newly invented PMX-F neutralizes a sufficient amount of endotoxin in vitro was reported previously. In ex vivo experiments, direct hemoperfusion by PMX-F was performed on purified endotoxin injected canine and on live Escherichia coli induced septic dogs. Only 5% (1/20) survived in the control group, but 75% (30/40) survived in the treated group. Septic dogs died within 18 hours after bacteria infusion in the control group. But all in the treated group survived 3 days. Forty percent of them survived permanently. These observations indicate that PMX-F treatment, namely selective removal of endotoxin in the endotoxic and septicaemic dogs prolongs or increases the chances of survival. Blood compatibility of PMX-F was also evaluated both in vitro and in vivo. With platelets it was shown to be fairly good and with red blood cells, white blood cells, and proteins, extremely good. A preclinical study on the efficacy and safety of PMX-F throughout widespread experiments has just ended.
Two cases of mixed medullary and follicular carcinoma of the thyroid (MFC) and two cases of thyroid carcinoma resembling MFC are reported with a description of their histological and immunohistochemical features. Two cases of MFC with lymph node metastasis were histologically distinguishable from each other because one had a follicular structure filled with a thyroglobulin (TG)-positive colloid-like substance and the other did not have it. Although one of the thyroid carcinomas resembling MFC was similar to the case of MFC with a follicular structure in its primary lesion, it showed no lymph node metastasis. The metastatic lesion of the thyroid carcinoma resembling MFC consisted of TG-positive cells and neighboring calcitonin (CT)-positive cells. However the primary lesion exhibited the typical features of papillary carcinoma except for the presence of a small lesion which stained negatively for both TG and CT. The two types of tumor were not intermingled in a single tumor. These cases of thyroid carcinoma resembling MFC have a possibility of being MFC. However they should not be classified as MFC because lymph node metastasis or the coexistence of medullary carcinoma and follicular carcinoma in their primary lesion was not proved.
The magnetic resonance findings in 22 children with athetotic cerebral palsy were studied. Sixteen had perinatal asphyxia, two had neonatal jaundice, and four had no association with predisposing conditions. In six of the children, symmetrical high intensity areas were found in both the thalamus and putamen in T2-weighted images. In five children they were seen only in the thalamus, and in another one only in the putamen. In six children, symmetrical periventricular high intensity areas were seen. In seven of the subjects, no abnormal magnetic resonance findings were seen. Magnetic resonance lesions, possibly caused by asphyxia, were found in the basal ganglia, thalamus and/or cerebral white matter in 14 of 16 children. Three children with lesions only in the cerebral white matter had mild motor abnormality, and six children with lesions in both the thalamus and putamen did not have mild abnormality.
The function of transplanted hepatocytes in acute ischemic liver failure was studied in an experimental model using rats. Ischemic liver failure was induced by occlusion of the proximal portal vein and hepatic artery immediately following extracorporeal portofemoral venous bypass. All rats were bred in a closed colony. Rats in Group 1 were untreated and served as controls (n = 10). Rats in Group 2 received an intrasplenic transplant of hepatocytes (1 x 10(7) cells) 48 h before liver ischemia (n = 10). Serum ammonia and blood glucose were measured before, and 1 h after, ischemia. Serum ammonia was significantly higher than normal (Group 1, 930 micrograms/dL vs < 110 micrograms/dL) after liver ischemia. On the other hand, serum ammonia in group 2 also was elevated (355 micrograms/dL), but significantly less so than in Group 1 (p < 0.001). Blood glucose was lower in both groups after liver ischemia, compared to normal (50-100 mg/dL), but it was higher in Group 2 (30 mg/dL) than in Group 1 (14 mg/dL, p < 0.01). Liver histology 1 h after ischemia showed similar degrees of necrosis in the two groups. Transplanted hepatocytes were viable, and clearly identified in the splenic parenchyma after ischemia. Intrasplenic transplanted hepatocytes provide temporary metabolic support of acute ischemic liver failure in rats, as reflected by enhanced ammonia removal and gluconeogenesis.
Bacterial infection results in the production of inflammatory mediators and may be involved in the pathogenesis of sepsis and/or systemic inflammatory response syndrome. The effect of lipopolysaccharide (LPS), a major component of the outer surface of Gram-negative bacteria, and Staphylococcal enterotoxin B (SEB), a superantigen of Gram-positive bacteria, on cytokine production in peripheral blood mononuclear cells (PBMCs) was examined. LPS significantly increased the production of proinflammatory and anti-inflammatory cytokines, and SEB enhanced the production of helper T lymphocyte type cytokines. These results illustrated the different responses to Gram-negative and Gram-positive bacterial infections. The effect of gabexate mesilate, a synthetic protease inhibitor, on cytokine production and expression of the toll-like receptor (TLR) was also examined. The results suggest that gabexate mesilate-induced inhibition of tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18) production in LPS-stimulated PBMCs is due to the inhibition of the nuclear factor-kappa B activation pathway and/or inhibition of the processing pathway of pro-TNF-alpha and pro-IL-18, not to down-regulation of TLR-2 or TLR-4.
Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-gamma (IFN-gamma), presents upstream of the cytokine activation cascade in the inflammatory response. The anti-inflammatory properties of steroids permit their use in various conditions, although effects are transient and pathological states are not fully relieved by short-term steroidal use. We examined the effect of lipopolysaccharide (LPS)/IL-2 on the cytokine cascade in human peripheral blood mononuclear cells (PBMCs). We also examined the effect of steroids on LPS/IL-2-induced cytokine production in human PBMCs taken from healthy volunteers. Cell-free supernatant fractions were assayed for IL-18, IL-12, IL-2, IFN-gamma and IL-10 protein, using enzyme-linked immunosorbent assays, and synergy between LPS and IL-2 in enhanced production of IL-18 was observed. Steroids suppressed the production of IL-18 and other secondary cytokines in LPS/IL-2-stimulated PBMCs, in a concentration- and time-dependent manner, although inhibition was incomplete even at high concentrations. Effects of steroid treatment on expression of membrane-bound LPS receptor antigen (mCD14) and intercellular adhesion molecule-1 (ICAM-1) in PBMCs were studied by flow cytometric analysis. Steroid treatment up-regulated mCD14 expression in a concentration-dependent manner, with no effect on ICAM-1 expression. These results suggest that the incomplete counteraction of steroids in the LPS/IL-2-initiating cytokine cascade is due, at least partly, to the up-regulation of mCD14 by steroid preparations, which increases susceptibility to bacterial endotoxins.
We have been investigating the mathematical nature of intercancer linkage that underlies the mutual regulation of cancer risks between any 2 tumors in their variations in time and space. Applications of both sequential regression test and topological manipulation of age-adjusted incidence rate (AAIR) data set enabled us to prepare the oncogene (Onc) activation profile and the tumor suppressor gene (TSG) inactivation profile for each tumor. The purpose of this study was to investigate the relation between the changes of 2 cancer gene profiles and the sex discrimination of cancer risk in 7 human neoplasias. Results obtained are as follows: i) The sex discrimination of cancer risk could better be defined by the use of log-transformed AAIR data rather than of untransformed AAIR data. ii) The sex discrimination of cancer risk, as calculated with the AAIR data of 47 population units of the world, is as follows: a) breast cancer (Br), M:F=1:120.2; b) thyroid cancer (Thy), M:F=1:2. 64; c) colon cancer (Co), M:F=1.18:1; d) liver cancer (Li), M:F=2. 63:1; e) lung cancer (Lu), M:F=3.66:1; f) esophageal cancer (Eso), M:F=3.68:1; g) laryngeal cancer (Lar), M:F=7.26:1. iii) Female-dominant cancers were associated with inversion (Br) or defectiveness (Thy) of male oncogene profile, whereas male-dominant cancers were associated with inversion (Lar) or defectiveness (Li, Lu and Eso) of female Onc profiles. Sex-indifferent cancer, Co, was distinguished from other tumors by the emergence of defectiveness in the TSG profiles of both sexes. TSG defectiveness was also detectable in female (Br, Thy) and bisexual (Lu) tumors. iv) The Onc vs TSG interaction, as assessed in terms of r value of the reciprocal regression analysis, was increasing in its positivity rate from the top of the female-dominant family (Br) through the sex-indifferent tumor (Co) to the bottom of the male-dominant family (Lar). In conclusion, the emergence of sex discrimination of cancer risk was positively correlated to the extent of integrity of oncogene activation in the dominant gender relative to the recessive gender. Findings with 6 sex-discriminant tumors are discussed in their relevancy to tumorigenesis from the point of view of endocrinological epidemiology.
We retrospectively analyzed 116 patients who underwent resection of stage IV gastric cancer to investigate the prognostic factors responsible for long-term survival. Statistically significant clinicopathological differences between patients surviving 3 years or more (n = 9) and those surviving less than 3 years (n = 107) were observed in regard to macroscopic type, curability of surgery, lymph node metastasis and blood vessel invasion. These four variables also had a statistically significant influence on survival by univariate analysis. Multivariate analysis revealed that no residual tumor (R0) surgery was a significantly beneficial factor for long-term survival. However, no patients with the diffusely infiltrative type of tumor survived for more than 2 years even if they underwent R0 surgery. Patients without the diffusely infiltrative type who underwent R0 surgery had better survival rates: a 27.3% and 13.6%, 3 and 5 year survival rate, respectively. In conclusion, R0 surgery contributes to long-term survival even in stage IV gastric cancer, and some patients with the not diffusely infiltrative type, in particular, may receive a survival benefit by R0 surgery.
The purpose of this study was to investigate the chronological changes in the age-adjusted incidence rates (AAIRs) of cancers of all sites as well as of 20 major cancers worldwide, which were tested using 5 consecutive IARC Data books from the early 1960s to mid-1980s. We used log-transformed AAIR data (log AAIR) for the statistical analysis of group data. For the follow-up study of a given neoplasia, we prepared 5 world populations using 5 international Data books, and calculated the mean and standard deviation of log AAIR for each tumor, for each sex and for each of 5 world populations for the follow-up study of cancer risks of 20 major cancers as well as cancers of all sites. The results obtained are as follows: a) the log AAIR of cancers of all sites, as compared between the early 1960s group and the mid-1980s group, significantly increased in both the male population (+32.1%) and the female population (+18.0%). b) The remarkable decrease of risks (log AAIRs) for cancers of the stomach and the uterine cervix (non-Western type cancers) and a remarkable increase of risks for cancers of the lung of both sexes, and of the female breast (Western type cancers), were observed from the early 1960s to the mid-1980s--a finding to indicate that the Westernization influences the cancer risk world-wide. c) The follow-up study of cancer risks of individual tumors in both individual population units and the world populations revealed the presence of a number of cancer risk changes that do not fit the definition of "Westernization of cancer risk pattern": i) an abrupt and remarkable increase of skin cancer risk that took place in both the East and the West in the time range of early 1960s to early 1970s; ii) a remarkable increase of liver cancer risk in both the East and the West in the early 1960s to mid-1980s; iii) sex-discriminative cancer risk increase, as exemplified by the contrast between significant risk increase of male sex organs (the prostate and the testis) and complete lack of risk increase in the female sex organs (the uterus and the ovary). d) Evidence was presented to suggest the possibility that some environmental hormone(s) may be implicated in the above changes in cancer risk that do not fit the definition of the "Westernization of cancer risk pattern". e) The importance of interdisciplinary exploration was stressed when assessing the scope of environmental hazards for both the risk of cancers of all sites and the reproductive activity of the human being.
The invention of 2 contrasting terms "Western type cancer" and "non-Western type cancer" implies that the progress of Westernization of life style for a given population may find its reflection in the balance of cancer risk between a Western type cancer and a non-Western type cancer. Our recent investigation presented evidence to indicate that the incidence of cancers of all sites increased by 32.1% (males) and 18.0% (females) from early 1960s to mid 1980s in the world statistics, and that the observed risk increase of cancers of the skin and liver did not fit the definition of "Westernization effect". It was suggested that the spread of environmental hormones could be related to the increased risks of 2 cancers. This study attempted to test the validity of the above statement by studying comparatively the epidemiological aspects of cancer of the skin, liver and breast, the latter being the reference tumor of the "Westernization effect". Cancer risk for each tumor was expressed in terms of the age-specific incidence rate (ASIR) and age-adjusted incidence rate (AAIR). For mathematical reasons, both ASIR- and AAIR-data were transformed into their logarithms before statistical analysis. We prepared the world population model with a size of 38 population units to investigate the relation between reproductive activity and cancer risk. Results obtained are as follows: a) the log AAIR of liver cancer was positively correlated to 2 parameters of reproductive activity in the female world population, and failed to show any correlation to the same 2 parameters in the male world population. The above finding was taken as evidence to indicate that liver cancer still retained its characteristics as a cancer of non-Western type with male predominancy of cancer risk. b) The log AAIR of skin cancer was negatively correlated to 2 parameters of reproductive activity in the world populations of both sexes--reconfirmation of skin cancer as of the Western type. c) In the period of early 1960s to mid 1980s the log AAIR of liver cancer of both sexes underwent exponential growth in Japan, slow and straight-line growth in 3 non-hispanic White populations, and no significant change in 2 Hispanic populations. d) The chronological follow-up study of log ASIR profile of both liver cancer in Japan and skin cancer in England revealed 3 common traits of cancer risk boost: i) quick and distinct ascension of cancer risk of all ages; ii) elongation of the young- age tail of the ASIR profile towards the 0 year limit; iii) emergence of a new infant type cancer profile independent of the existing adult type cancer profile. Possible implication of environmental hormones in human embryogenesis was suggested as an explanation for the genesis of an infant type cancer. e) Comparative study of log ASIR profiles of breast cancer between England and Japan did not support possible implication of environmental hormones in the recent rise of breast cancer risk throughout the world. f) The eligibility of cancers of the liver and skin as the targets of environmental hormones was discussed in the light of up-to-date data of epidemiology and experimental pathology.