Masakatsu Yamamoto

Immunohistochemical study of carcinoembryonic antigen in patients with colorectal cancer. Correlation with plasma carcinoembryonic antigen levels

Using peroxidase‐antiperoxidase (PAP) method, carcinoembryonic antigen (CEA) was demonstrated in conventionally processed colorectal cancer tissues. A new immunohistochemical grading for colorectal cancers based on the mode of the localization was made in an attempt to clarify the factors responsible for elevation of plasma CEA levels in colorectal cancer patients. Most of the patients with well differentiated adenocarcinoma, in which CEA was densely distributed along the apical surface but only rarely present along the basolateral surfaces of the carcinoma cells, had very low levels of plasma CEA, whereas all patients showing CEA distribution in the stroma as well as over the entire surfaces of the cancer cells and their cytoplasm showed high plasma CEA levels. In addition, there was a good correlation between the grading and presence of the blood vessel and lymphatic invasions. Thus, the appearance of CEA in the surrounding stroma, due to abnormal distribution of CEA on the basolateral plasma membrane of cancer cells, may play a significant role in the elevation of plasma CEA levels in colorectal cancer patients.

Physiologic and anatomic assessment of patients with rectocele.

Clinical, physiologic, and anatomic assessments were carried out in 22 female patients with symptomatic rectocele (Group A), 15 patients with asymptomatic rectocele (Group B), and 14 subjects having no rectocele (Group C). Resting anal pressure, rectal pressure, rectal compliance, anorectal inhibitory reflex, and rectal sensation did not differ among the groups. Proctography revealed that the lengths of the rectocele during attempted defecation in groups A (1.6 [1.0–3.5] cm) (median and range) and B (1.6 [1.0–3.0] cm) were significantly greater than that in Group C (0.4 [0.1–0.9] cm) (P<0.001 in both groups). Median pelvic floor descent at rest in Groups A (4.3 [1.6–7.5] cm) (median and range) and B (4.3 [1.3–6.9] cm) were significantly greater than that in Group C (2.5 [1.2–5.0] cm) (P<0.001 andP<0.02, respectively). These results indicate that rectocele is not associated with any physiologic change apart from a significant increase of pelvic floor descent.

Structural and functional alterations in the gut of parenterally or enterally fed rats

Various regimens of total parenteral nutrition (TPN) and enteral feeding were compared to determine their effects on the structural and functional changes of rat small intestine. Male Wistar rats, allocated randomly into five groups on the basis of delivery route and composition of nutrients, were fed as follows: standard rat chow ad libitum (CE-2 group), low-residue diet (LRD group), LRD supplemented with 1% (w/v) fiber (LRD + fiber group), elemental diet (ED group), and TPN (TPN group). At 2 weeks of feeding, villi in the terminal ileum decreased in height in the following order: CE-2 group greater than LRD + fiber group greater than LRD group greater than ED group greater than TPN group. Mucosal diamine oxidase activity remained unchanged in the CE-2 group and LRD + fiber group throughout the experimental period. However, mucosal diamine oxidase values were significantly lower in the remaining three groups, similar to the structural changes, and those values in the ED group were significantly decreased at 2, 3, and 4 weeks. There was a positive correlation between plasma diamine oxidase level and mucosal diamine oxidase content, with a coefficient correlation of y = 0.20x + 0.03, r = 0.55 (P less than 0.01). These results could be interpreted to indicate that addition of dietary fiber to LRD has a favorable effect on the maintenance of intestinal architecture and function during enteral feeding, and plasma diamine oxidase activity can be used as an index of functional and/or structural changes occurring in the small intestine during enteral or parenteral feedings.

Endocrine cells and prognosis in patients with colorectal carcinoma

Using chromogranin (CG) immunohistochemical staining, the prognostic significance of endocrine differentiation was investigated in 212 patients with primary colorectal adenocarcinoma (including 6 patients with mucosal carcinoma). CG‐immunoreactive cells were found to be an integral component of the tumor in 67 of 206 patients (32.5%, excluding mucosal carcinoma). The intra‐cellular localization of CG in the CG‐immunoreactive cells in cancer tissue was completely different from that in the normal endocrine cells of the large bowel. In addition, morphologic changes such as nuclear hyperchromasia and pleomorphism also indicated that the CG‐immunoreactive cells in the cancer tissue were malignant. The tumors were divided into three groups based on the frequency of CG‐immunoreactive cells: Group I (n = 139), negative; Group II (n = 38), less than 1 positive cell/mm2; and Group III (n = 29), more than 1 positive cell/mm2. No correlation was observed between CG‐immunoreactivity (CG‐IR) and tumor location, grade, depth of invasion, or stage, regardless of lymph node involvement. However, patients with numerous endocrine tumor cells (Group III) had a significantly worse prognosis compared with patients without endocrine cells (Group I) (multivariate Coxs model, P < 0.01). Similar findings were observed in patients with node‐negative tumor (multivariate Coxs model, P < 0.05). These results indicated that the neuroendocrine differentiation is an independent prognostic factor and that CG‐immunohistochemistry is useful for detecting a subgroup with a worse prognosis among patients with colorectal cancer.

Risk factors in relation to postoperative complications in patients undergoing esophagectomy or gastrectomy for cancer.

To clarify the risk factors contributing to postoperative complications in the elderly patients (over 70 years) undergoing esophagectomy and/or gastrectomy, 364 patients with primary cancer seen were evaluated. As a result, some characteristic patterns of stress response in the elderly could be detected as follows: the disorders of the vital organs were more important indices for the development of postoperative complications rather than age, and a reduction in the maximum response of the stress hormones to surgical procedures in aged patients was noted; moreover, the functional variability of target organ in the aged group was confirmed. Studies on the hormonal response to surgery suggest that the restriction of fluid replacement is advisable until the third postoperative day, maintaining the host on the dry side, to prevent cardiopulmonary complications. As the nutritional status in the patients with esophageal and gastric cancer goes from bad to worse with the advancing clinical stages, adequate perioperative nutrition is imperative to prevent complications such as anastomotic leakage, wound dehiscence, and/or infections. For the treatment of anastomotic leaks after esophagectomy and esophagogastrectomy, more than 45 kcal/kg/d must be provided, and the serum albumin level must be restored to 3.5 g/dL in order to achieve spontaneous healing of small anastomotic leakages.

Preoperative nutritional assessment to predict postoperative complication in gastric cancer patients

The correlation between preoperative nutritional parameters and postoperative complications in 440 patients with gastric cancer were analyzed. All the nutritional parameters reflected a significant deterioration as the stages of cancer progressed, and the frequency of postoperative complications was highest in patients with stage IV gastric cancer. The incidence of anastomotic leaks was increased in patients undergoing total gastrectomy with no relation to the clinical stage or nutritional status. However, there was a close relationship between nutritional status and immunocompetence, lung complications, and infection. The nutritional indices which reliably predicted preoperatively the nutritional status of cancer patients were the serum protein concentrations including the serum albumin (Alb) and prealbumin (PA). The indices predicting postoperative complications were the Alb, PA, and total lymphocyte count. These results suggest that preoperative nutritional assessment can be beneficial for the prediction of postoperative complications.

Effect of human recombinant interleukin-6 on the proliferation of mouse hepatocytes in the primary culture

Effects of various cytokines on the proliferation of mouse hepatocytes were investigated. Human recombinant IL-6 not only enhanced the proliferation of mouse hepatocytes in the presence of epidermal growth factor, but also without epidermal growth factor. However, other human or mouse cytokines such as recombinant IL-1, IL-2, IL-3, IL-4, IFN-beta and IFN-gamma, which are known to regulate immune responses and/or hematopoiesis, had no effect on the proliferation of hepatocytes. These results suggest that IL-6 plays a crucial role in regulating the regeneration of hepatocytes after hepatitis or partial hepatectomy.

Effect of Various Lipid Emulsions on Total Parenteral Nutrition-Induced Hepatosteatosis in Rats

The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups.

Different mechanisms of action of histamine in isolated arteries of the dog.

1 In helically‐cut strips of dog coronary, superior mesenteric, right gastro‐epiploic and renal arteries contracted with prostaglandin F2β (PGF2β), histamine produced a dose‐related relaxation, while, in contrast, the amine caused only a contraction of cerebral arterial strips 2 The contractile response of cerebral arteries to histamine was attenuated by chlorpheniramine (10−6M)but was unaffected by cimetidine (10−5m). Relaxant responses to histamine of coronary and renal arteries were significantly attenuated by treatment with cimetidine and to a similar extent by combined treatment with cimetidine and chlorpheniramine. Chlorpheniramine alone was ineffective 3 In mesenteric and gastro‐epiploic arteries, relaxant responses to histamine were attenuated only slightly by cimetidine. Chlorpheniramine slowed the development of histamine‐induced relaxations but did not alter the magnitude of the relaxations. Combined treatment with these H1‐ and H2‐ antagonists attenuated the histamine‐induced relaxations to an appreciably greater extent than treatment with cimetidine alone 4 It may be concluded that the cerebroarterial contraction induced by histamine is mediated through H1‐receptors and the relaxations of coronary and renal arteries induced by histamine are mediated through H2‐receptors. It appears that H1‐ and H2‐receptors interact with each other to produce potentiation of histamine‐induced relaxations of mesenteric and gastro‐epiploic arteries.

Immunohistochemical staining patterns of tenascin in invasive breast carcinomas

Eighty-two cases of primary invasive breast carcinoma and adjacent “normal” mammary glands were examined immunohistochemically for tenascin expression and distribution. Formalin-fixed tissues pretreated with actinase were processed by the avidin-biotin complex method using anti-human tenascin monoclonal antibody (RBC1). In normal mammary glands, tenascin was distributed around the ducts and ductules but not around the acini. In carcinomas, a high incidence of tenascin-positive cases (>67%) was seen with various histological appearances, with the exception of lobular carcinoma where a low incidence was found (25%). Although intense staining was seen around cancerous foci when compared with normal mammary glands, tenascin was often expressed at cancer-mesenchymal junctions with dense fibrotic stroma, but not at junctions with active inflammatory change and a loose fibrotic stroma. Tenascin expression is not an all-or-none marker for mammary malignancy and the staining pattern suggests either a role in stimulating cancer cells or a host defence mechanism accompanied by a desmoplastic response to them.