Macroscopic assessment of nodal metastasis is not reliable in colon cancer

Background Japanese surgeons have to macroscopically assess nodal metastasis from colon cancer according to the general rules established in Japan. Adjuvant therapy is sometimes started after macroscopic assessment of nodal metastasis. Macroscopic assessment, however, is difficult in many cases. Methods We evaluated the reliability of macroscopic assessment of nodal metastasis in colon cancer by (1) comparing the number of nodes picked up macroscopically with that of nodes recognized microscopically, and (2) by comparing the number of metastatic nodes found between macroscopic and microscopic examination. Results The number of nodes found during macroscopic examination was equal to that found in microscopic examination in only 52 of 206 cases (25%). Although 120 of 206 cases (58%) were judged macroscopically to have metastatic nodes, 61 had no metastatic nodes found microscopically. Sensitivity and specificity for the recognition of cases with nodal metastasis was 85.5% and 55.5%, respectively. The number of metastatic nodes in macroscopic examination was equal to that in microscopic examination in 90 cases (44%). Conclusion Because macroscopic assessment of nodal metastasis is not reliable, physicians should not rely on macroscopic assessment to indicate the need for further therapy, such as adjuvant chemotherapy. The recommendation for macroscopic assessment of nodal metastasis should be eliminated from the general rules in Japan.     

Homotypic Adhesion through Carcinoembryonic Antigen Plays a Role in Hepatic Metastasis Development

We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of liver-metastatic cells in SCID mice. This cell line strongly expressed CEA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay. Further, to study the role of CEA in the hepatic metastasis of cells with high metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the inhibition of hepatic metastasis after splenic injection in vivo was examined. There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated (100 μg/ml) LS-LM4 cells under a Ca²⁺-free condition as compared with the control ( P <0.01). Anti-CEA antibody (100 μg/ml) inhibited cell aggregation under a Ca²⁺-free condition ( P <0.05). Treatment with anti-E-cadherin antibody (60 μ/ml) plus anti-CEA antibody (100 μg/ml) inhibited cell aggregation more potently than anti-E-cadherin antibody treatment alone in the presence of Ca²⁺. In vivo , there was a 75% decrease in the number of hepatic metastatic nodules in the G125 anti-CEA antibody-treated group as compared with the control group ( P <0.01). Similarly, there was a 40% decrease in the diameter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated group as compared with the control ( P <0.01). These results suggest that increased metastatic potential to the liver is at least partly due to increased homotypic binding mediated by CEA.     

D1 dopamine receptor activation reduces extracellular glutamate and GABA concentrations in the medial prefrontal cortex

The present study examined effect of administration of a selective D1 dopamine receptor agonist, SKF38393 on extracellular concentrations of glutamate (Glu) and gamma-aminobutyric acid (GABA) in mPFC, by using in vivo microdialysis. Perfusion with SKF38393 via a dialysis probe reduced concentrations of both Glu and GABA dose-relatedly, and these effects were prevented by co-perfusion with a D1 dopamine receptor antagonist, SCH23390 (40 microM). These results suggested that the dopaminergic hyperactivity may lead to the hypofunction of glutamatergic and GABAergic systems in mPFC via D1 dopamine receptor stimulation.     

Autologous blood transfusion in patients with hepatocellular carcinoma undergoing hepatectomy

BACKGROUND: Homologous blood transfusion (HBT) has the risk of an immunosuppressive effect and may adversely affect the prognosis of patients with carcinomas. Autologous blood transfusion (ABT) has not yet become a standard procedure in gastroenteric cancer surgery. We investigated the usefulness and problems of ABT combined with the use of recombinant human erythropoietin (rh-EPO). METHODS: An evaluation of autologous blood transfusion (ABT) combined with recombinant human erythropoietin (rh-EPO) treatment was conducted in 46 patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative autologous blood donation (ABD) was accomplished for 25 of the 46 patients. The preoperative changes in hemoglobin and hematocrit in relation to route of administration of erythropoietin were studied. In addition, intraoperative blood requirements and the postoperative complications for patients who predonated were compared with those of patients who underwent surgery without autologous predonation. RESULTS: The proportion of patients not requiring additional homologous blood transfusions (HBT) during operation was significantly higher in the ABD group than in the non-ABD group (88% versus 38%). The incidence of postoperative complications was significantly higher in patients receiving HBT than in nontransfused patients and in those receiving ABT. CONCLUSIONS: Preoperative autologous blood donation in combination with rh-EPO therapy markedly reduced the requirement for homologous blood transfusion during surgery in patients with hepatocellular carcinoma having hepatectomy.     

Morbidity and mortality after 94 extrapleural pneumonectomies for empyema

BACKGROUND: Extrapleural pneumonectomy is still indicated in some patients with empyema. We examined morbidity and mortality after this high-risk operation. METHODS: Between 1979 and 1998, 94 (92 chronic, 2 postsurgical) patients with empyema underwent extrapleural pneumonectomy. There were 79 men and 15 women (mean age, 59 years). Eighty-eight patients had a history of tuberculosis, and 53 had undergone a therapeutic pneumothorax. The right side was operated on in 50 patients and left in 44. RESULTS: Operative mortality was 8.5%. Fifteen major complications (1 esophageal perforation, 9 empyemas, and 5 bronchopleural fistulas) occurred in 13 patients. Eight patients required reexploration for hemorrhage. Reexploration was a risk factor for empyema. Bronchopleural fistulas occurred only on the right side. Eighty-nine percent of the 86 operative survivors were free of empyemas at 5 years. Overall 5-year survival was 83%, and survival was better in patients without than in those with empyema. CONCLUSIONS: Extrapleural pneumonectomy for empyema has acceptable morbidity and mortality. Postoperative empyema affects prognosis. Covering a bronchial stump with muscle is recommended, especially when the operation is performed on the right side.     

Redo without transfusion in a patient with idiopathic thrombocytopenic purpura

Mitral valve replacement was able to be carried out at redo operation requiring neither allogeneic platelet nor blood transfusion in a patient with idiopathic thrombocytopenic purpura, by means of preoperative high-dose intravenous gamma-globulin, autologous blood predonation, use of a centrifugal pump, heparin-coated extracorporeal circuits, and simultaneous splenectomy.     

Differences in gut integrity following abdominal surgery according to the magnitude of the surgical stress

BACKGROUND: An increase in serum diamine oxidase (DAO) activity reflects intestinal mucosal damage. This was used to estimate the effect of surgical stress after elective abdominal surgery on gut integrity. METHODS: Patients with gastrointestinal tract cancers were placed in either group T (transthoracic esophagectomy for esophageal cancer, n = 9) or group L (laparotomy, n = 10). The serum DAO activity was measured pre-operatively, and on postoperative days 1, 3, and 8. RESULTS: Transthoracic esophagectomy was associated with a more extensive stress than the operations in group L, as measured by the intra-operative blood loss, the amount of blood transfused, and the operative time (P = 0.007, P = 0.0002, P = 0.0011, respectively). Following surgery, the serum DAO activity was decreased markedly in all patients in group T. In contrast, the activity was unchanged in group L (P = 0.04). CONCLUSIONS: The severity of the surgical insult plays a significant role in the decrease in serum DAO activity. These results suggest that surgical stress influences gut integrity following elective abdominal surgery.     

A novel compound RS-0466 reverses beta-amyloid-induced cytotoxicity through the Akt signaling pathway in vitro

In order to determine whether 5-[bis(carboxymethyl) amino]-2-carboxy4-cyano-3-thiopheneacetic acid distrontium salt (S12911-2) inhibits bone resorption by acting on the differentiation and/or function of osteoclasts, its effects were assessed on the 1,25-dihydroxyvitamin D(3)-induced expression of carbonic anhydrase II and vitronectin receptor in chicken bone marrow cells, and on the resorbing activity of authentic rat osteoclasts cultured on bone slices. S12911-2 dose-dependently inhibited, after a 6-day exposure, the expression of carbonic anhydrase II and vitronectin receptor in stimulated osteoclasts (46% and 40%, respectively, at 10(-3) M Sr(2+), P<0.05). A pre-incubation of bone slices with S12911-2 induced a dose-dependent inhibition of bone resorbing activity from 32% at 10(-4) M Sr(2+) to 66% at 10(-3) M Sr(2+) (P<0.05 in each case). A continuous incubation (10(-3) M Sr(2+)) induced a greater inhibition of bone resorbing activity (73%, P<0.05). The inhibition of bone resorption obtained specifically with S12911-2 is related to an inhibition of the differentiation and resorbing activity of the osteoclasts.