Massive melena from acute mucosal necrosis after sigmoidectomy.
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Biomedical subjects
Publications and source records attributed to M Shimotsuma.
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A new drug dosage form comprising activated carbon particles absorbing mitomycin C (MMC-CH) has the advantage of being retained in the peritoneal cavity and distributes a larger amount of mitomycin C for a long time. Some 113 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with MMC-CH and no anti-cancer drugs. There were significant differences in survival rate between the patients who have no visible peritoneal dissemination with MMC-CH and without. Thus, intraoperative intraperitoneal treatment with MMC-CH improves survival after gastrectomy for gastric cancer and seems effective against peritoneal recurrence.
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We examined the site-specific implantation of cancer cells in peritoneal tissues after an i.p. inoculation of 10(5) P388 leukemia cells. Twenty-four h after the inoculation, the number of viable cancer cells infiltrating into specific tissue sites of the peritoneum was estimated by an i.p. transfer method. A descending order of tissue implantation with cancer cells was established as omentum > gonadal fat > mesenterium > posterior abdominal wall > stomach, liver, intestine, anterior abdominal wall, and lung. A significant correlation was established between the logarithm of the number of infiltrating cancer cells and the logarithm of the number of milky spots. Next, the omentum was examined microscopically after i.p. inoculation with P388 leukemia cells labeled with bromodeoxyuridine or B-16 PC melanoma, which were differentiated from the other cells by an immunocytological method using anti-bromodeoxyuridine antibody or by the melanin of the B-16 PC melanoma cells. These cancer cells were found microscopically to be infiltrating only the milky spots, whereas none were seen at the other sites. These results suggest that cancer cells seeded i.p. specifically infiltrate the milky spots in the early stage of peritoneal metastases.
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Two cases of severe lactic acidosis induced by total parenteral nutrition (TPN) are reported. Both cases were admitted to our department for the surgical treatment of advanced gastric cancer, and subsequently underwent TPN because of poor nutritional status. Following the initiation of TPN, both patients went into an unstable circulatory state following shock. Both cases showed signs of peritonitis, suggestive of an intraabdominal abscess, and subsequently underwent an emergency laparotomy to explore the origin of the lactic acidosis. There was, however, no apparent infectious focus which would lead to severe metabolic acidosis in the abdominal cavity. One case died of irreversible shock. The other case similarly exhibited a deteriorated cardiovascular state but promptly responded to the administration of thiamine and was resuscitated. The blood thiamine level was low in both individuals, and the two patients were subsequently diagnosed as having thiamine deficiency-induced lactic acidosis.
A simple and reliable technique is described for in situ excision of distended samples of greater omentum from small laboratory animals. The omental bursa is distended by injecting whipped hen egg white. Filter paper frames then are applied to the selected areas of distended omentum and samples of omental membrane are excised together with the filter paper frames. This sampling technique yields undamaged materials suitable for various research purposes.
We have developed a new dosage form, PEP-CH, consisting of peplomycin adsorbed onto small activated carbon particles. Ten patients with inoperable advanced esophageal cancer were treated with endoscopic local injection of PEP-CH combined with radiation using 60Co. Two of 5 patients who completed the treatment have survived over one year (19 and 23 months) now.
The morpho-physiological function and role of milky spots in the greater omentum are reviewed. These milky spots are composed of cellular aggregations of mesenchymal cells, mainly macrophages and lymphocytes, surrounding capillary convolutions termed omental glomeruli. Initial lymphatics of the omentum begin at the milky spots and drain into lymph collectors. The lymphatic capillaries in the omental milky spots take part in the absorption of various substances from the peritoneal cavity. Omental milky spots probably act as the first line of defense in the peritoneal cavity and therefore are immunologically important. In human infants, most of the cells in these milky spots are macrophages (49%); less common are B lymphocytes (29%) and T lymphocytes (12%). Whereas macrophages form clusters near the peritoneal surface of the milky spots and are oriented toward the peritoneal cavity for migration, clusters of B and T lymphocytes are typically found in periarteriolar locations within the milky spots. This cell zonation facilitates phagocytosis and processing of circulating antigens and foreign bodies which emanate from the peritoneal cavity. During inflammation, the number and size of omental milky spots dramatically increase, and some develop germinal centers within the lymphatic follicles and produce antibodies. During intraperitoneal immunotherapy, the omental milky spots and their cellular elements may be activated by intraperitoneal administration of biological response modifiers, and thereby represent an important immunoregulatory system for the peritoneal cavity. Omental milky spots are also closely linked to the dissemination of cancer cells. Thus, intraperitoneally inoculated experimental tumor cells selectively invade the milky spots and proliferate there to form tumor nodules. This occurrence is relevant to clinical practice where nodular metastases to the omentum are common. Omental milky spots are analogous to regional lymph nodes and as such are the omentum-associated lymphoid tissues and participate in intraperitoneal immune reactions.
TNP-470, an analog of fumagillin, is one of the new angiogenesis inhibitors. Five days after an intraperitoneal inoculation of 10(7) cells of Walker 256 carcinosarcoma to SD rats, TNP-470 was injected intraperitoneally in the form of TNP aqueous solution or TNP-oil solution. Mean survival time of rats given TNP-oil solution or TNP aqueous solution was statistically prolonged, compared with that of the control rats. Our results showed that TNP-470 is an effective therapeutic drug for carcinomatous peritonitis.
A new dosage format (MMC-CH) of mitomycin C, which is composed of mitomycin C on activated carbon particles, was efficacious for prevention of peritoneal recurrence of gastric cancer. However, it had no such excellent therapeutic effect on the survival of patients with peritoneal dissemination. Out of 50 patients with peritoneal dissemination of gastric cancer treated by intraperitoneal administration of MMC-CH, 4 patients have survived for long periods of time (39-80 months). However, all of the other 50 patients, who did not receive intraperitoneally administered MMC-CH, died of peritoneal carcinomatosis within two years.
Omental milky spots are omentum-associated lymphoid tissues that cede peritoneal macrophages and participate in the immunity of the peritoneal cavity. We studied the changing surface features of milky spots and milky spot macrophages of Wistar rats, following the i.p. administration of OK-432, a killed streptococcal preparation (1 Klinische Einheit (unit) in 5 ml of phosphate-buffered saline) by the use of scanning electron microscopy. OK-432-activated macrophages demonstrated marked surface membrane activity and migrated through the stomata of the milky spot into the peritoneal cavity. The characteristic features of activated milky spots and milky spot macrophages were noted as early as 3 h following the administration of OK-432, and continued to be observed until 7 days after the injection. By 14 days after the injection, the structural integrity of the milky spot was partially lost. The activation of milky spots and milky spot macrophages by OK-432 provides a convenient in vivo system for the monitoring and study of i.p. cellular events.
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A method is described for flat-embedding thin membranous tissues in Historesin. It allows easy orientation for sectioning large areas parallel to the surface. Selected fields can be monitored from the unfixed specimen, throughout preparation, to mounting on the microscope slide. For cross-sectioning, the flat-embedded tissue can be stacked and re-embedded to increase the amount of material examined per section.
CH40 and CH1500AA are newly prepared carbon suspensions which were examined as vital staining dyes for their usefulness in visualizing lymphatics at operation and to blacken lymph nodes. In mice, these carbon suspensions at 0.001 ml/g of body weight and India ink were injected subcutaneously into the footpad of the right hindpaw. Regional lymph nodes were visualized and were examined stereomicroscopically to determine how intensely these nodes blackened with carbon suspensions. Compared with India ink, CH40 and CH1500AA blackened the regional lymph nodes much faster and more vividly (1-8 min. after subcutaneous injection). As analyzed by centrifugal particle size distribution, CH40 and CH1500AA are narrowly distributed with a small particle size (150 and 167 nm, respectively, in mean diameter). By contrast, India ink is comprised of widely distributed and relatively large particles in suspension (mean diameter--254 nm). In 10 patients undergoing radical gastrectomy for treatment of stomach cancer, CH40 blackened 69% of regional lymph nodes with metastases (38 of 55) and 76% of those nodes without metastases (387 of 512).
Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.