Conditions required for a hybrid artificial liver support system using a PUF/hepatocyte-spheroid packed-bed module and it's use in dogs with liver failure

We studied the effects of a hybrid artificial liver support system we developed on dogs with hepatic failure. The system consisted of a multi-channel polyurethane foam packed-bed culture module, including primary dog hepatocyte spheroids. Blood ammonia was well metabolized by 20 g hepatocytes, but the other functions such as glucose concentration, total bile acid concentration, and survival time required 30 g hepatocytes to improve conditions. We found that we should use a culture substratum that easily forms spheroids, and that an artificial liver module should be used as soon as possible after spheroid formation by hepatocytes in the module.     

Effect of tacrolimus on endotoxin-induced lung injury in sheep

Since tacrolimus (FK-506) is known to suppress the proliferation and generation of T cells and to inhibit the production of T cell derived cytokines, we examined the effect of FK-506 on endotoxin-induced lung injury. We administered FK-506 (0.1 mg/kg) intravenously before the infusion of endotoxin (1 microgram/kg) into conscious sheep. We measured pulmonary hemodynamics, lung fluid balance, circulating leukocyte count and arterial blood gas tensions. The increase in pulmonary arterial pressure was significantly attenuated by FK-506 during the late period (3-5 h after endotoxin). Arterial oxygen gas tension was significantly higher in the FK-506 treated sheep during this phase. However, no significant differences were observed in lung lymph balance and circulating leukocyte count between the endotoxin alone group and the FK-506 treated group. These findings suggest that FK-506 may improve gas exchange in acute lung injury although there is an increased pulmonary vascular leakage. It is probable that FK-506 may have a beneficial potential on endotoxin-induced lung injury in sheep.     

Inhibition of tumor necrosis factor-alpha-induced RANTES secretion by alkaline protease in A549 cells

Pseudomonas aeruginosa is a gram-negative bacterium that is an opportunistic pathogen in patients with cystic fibrosis and in immunocompromised hosts. This bacterium produces a variety of proteolytic enzymes, including alkaline protease (AP), which has multiple biological effects. This study investigated the effects of AP on the A549 pulmonary epithelial cell line. Results demonstrate that AP inhibited tumor necrosis factor (TNF)-alpha-induced RANTES gene expression and secretion in a concentration-dependent manner. The TNF-alpha-induced RANTES gene expression and secretion was attenuated with a neutralizing monoclonal antibody directed against the TNF receptor type 1 (TNFR1). Conversely, a neutralizing monoclonal antibody directed against TNF receptor type II had no effect, suggesting that these events were regulated through the TNFR1 receptor. In addition, we observed that soluble TNF receptor type 1 (sTNFR1) levels were significantly increased in culture supernatants of AP-treated cells in a concentration-dependent manner. Finally, membrane-associated TNFR1 was decreased after AP exposures. In these studies, the enzymatically inactive form of AP had no effect on TNF-alpha-induced RANTES secretion, shedding of sTNFR1, or membrane-associated TNFR1. These results demonstrate that AP stimulates shedding of cell-surface TNFR1, resulting in an increase in sTNFR1. Consequently, these events decrease the cells' ability to stimulate RANTES gene expression and secretion through TNFR1.     

Concomitant presence of inflammatory fibroid polyp and carcinoma or adenoma in the stomach

Four instances (8%) of inflammatory fibroid polyp (IFP) with concomitant adenocarcinoma or adenoma, in the same area, were noted among 50 cases of IFP of the stomach. Adding two cases from other sources, four cases of gastric IFP concomitant with an adenocarcinoma and two of gastric IFP concomitant with an adenoma were studied histopathologically and immunohistochemically. All lesions were located in the gastric antrum and they were restricted to the mucosa in three, and they involved both mucosa and submucosa in the other three. Neither S100 protein nor factor VIII-associated antigen was recognized in the principal component cells, using an immunoperoxidase technique. This finding suggests the conventional view that the proliferating cells were neither neurogenic nor angioblastic, but rather, were fibroblastic in origin. The four concomitant carcinomas were early adenocarcinomas restricted to within the mucosa, and the two concomitant adenomas were tubular adenomas with a moderate epithelial atypia. All these neoplasms were present in or adjacent to the IFP. We emphasize that the IFP, albeit benign, may carry an adenocarcinoma or an adenoma.     

Combination chemotherapy with methotrexate and 5-Fluorouracil and surgery for advanced gastric-cancer with liver and lymph-node metastases - a case-report

We report on a case of advanced gastric cancer with multiple liver metastasis and lymph node metastases in a 65-year-old Japanese man. He was treated with sequential intravenous administration of moderate-dose methotrexate 1 (MTX) and 5-fluorouracil (5-FU) preoperatively. After eleven cycles of the combination chemotherapy, the findings of liver and lymph node metastases diminished dramatically and the tumor could be resected for a potential cure, using a total gastrectomy and combined hepatectomy. The resected specimen revealed a slightly elevated lesion and a somewhat shallow ulceration due to chemotherapy. Histologically, there was an infiltration of poorly differentiated adenocarcinomas with medullary structure in the muscularis mucosae with fibrous change. The liver was metastasized, but there was no evidence-of lymph node metastasis. We believe that combination chemotherapy of MTX and 5-FU can be effective against gastric cancer.     

Strategy for lymphadenectomy in lung cancer three centimeters or less in diameter

We have surgically treated 221 patients with a primary lung cancer 3.0 cm or less in diameter. There were 8 patients with a tumor 1.0 cm or less in diameter (group A), 84 with a tumor 1.1 to 2.0 cm in diameter (group B), and 129 with a tumor 2.1 to 3.0 cm in diameter (group C). The incidence of N0, N1, and N2 disease was 100%, 0%, and 0%, respectively, for patients in group A; 83%, 5%, and 12% in group B; and 62%, 12%, and 25% in group C (N0 versus N2, p less than 0.01). For the 63 patients with regional lymph node involvement, "skipping" metastasis was present in 28.6%. The 5-year survival rate was 80% for group A, 74% for group B, and 51% for group C (group B versus group C, p less than 0.01). Of the 121 patients who underwent complete resection and were followed up for 5 years, 41% had recurrence, 8% with local recurrence and 33% with distant metastasis. Therefore, it is important to do as complete a resection as possible together with mediastinal lymphadenectomy. Efforts to detect systemic spread should be made at the time of preoperative evaluation, even when the lung tumor is small.     

Operative procedures of reconstruction after resection of esophageal cancer and the postoperative quality of life

To investigate the influence of the operative procedures of reconstruction after resection of esophageal cancer on the postoperative quality of life, an interview was conducted and subjective and objective factors related to the quality of life were evaluated in 50 patients without a recurrence of esophageal cancer. Among the 50 cases, reconstruction by the antethoracal route was performed in 9 (group I) and by the retrosternal route in 24 (group II). Intrathoracic anastomosis was done in 17 (group III). A postoperative disturbance of the food passage was seen 22.0, 41.6, and 5.9% in groups I, II, and III, respectively. Dumping symptom was evident 11.1, 12.5, and 11.8%, respectively. Heartburn was seen only in two cases, in group III. A body weight loss of more than 1.0 kg from preoperative weight was seen in 33.3, 41.7, and 41.2% of groups I, II, and III, respectively. There was no difference in the postoperative performance status or laboratory data among the groups. Thus, although intrathoracic anastomosis was favorable for postoperative food passage, there was no significant difference in any other factors in the quality of life among the routes of reconstruction, and the quality of life gradually improved in patients of all groups as postoperative time passed in the cases without postoperative recurrence of esophageal cancer.

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Resumen Con el propósito de determinar la influencia sobre la calidad de vida de los procedimientos operatorios de reconstrucción luego de la resección de un cancer esofágico, se realizaron entrevistas para valorar los factores tanto subjetivos como objetivos relativos a la calidad de la vida en 50 pacientes libres de enfermedad recurrente. En este grupo de 50 pacientes se practicó reconstrucción por la vía anterotorácica en 9 (Grupo I), por la ruta retroesternal en 24 (Grupo II) y se practicó anastomosis intratorácica en 17 (Grupo III). Se demostró alteración en el paso de los alimentos en 22.0%, 41.6% y 5.9% en los Grupos I, II y III, repectivamente; se evidenciaron sítomas de dumping en 11.1%, 12.5% y 11.8% en cada grupo. Sólo se encontró pirosís en dos casos en el Grupo III. Pérdida de peso mayor de 1.0 kg frente al peso preoperatorio fue obsevada en 33.3%, 41.7% y 41.2%, respectivamente. No hubo diferencia en cuanto a la actividad física postoperatoria ni en los hallazgos de laboratorio entre los grupos. Por lo tanto, aunque la anastomosís intratorácica es más favorable en cuanto al buen paso de los alimentos, no se evidencian diferencias significativas en los demás factores pertinentes a calidad de vida entre las diferentes rutas de reconstrucción, y la calidad de la vida mejoró paulatinamente en todos los grupos con el paso del tiempo en estos pacientes libres de recurrencia postoperatoria de su cáncer esofágico.

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Résumé Pour étudier l'influence des différentes techniques de reconstruction après résection pour cancer de l'esophage sur la qualité de vie postopératoire, on a interviewé 50 patients opérés et indemnes de récidive. Parmi ceux-ci, 9 avaient eu une reconstruction en position présternale (group 1), 24 par une voie rétrosternale (groupe 2) alors que 17 avaient eu une anastomose intrathoracique (groupe 3). Des difficultés d'alimentation ont été observées chez respectivement 22; 41.6 et 5.% des patients dans les groupes 1, 2 et 3. Un syndrome de dumping a été observé chez respectivement 11.1, 12.5 et 11.8%. Un pyrosis n'a été noté que dans deux cas du groupe 3. Une perte de poids supérieure à un Kg a été observée chez respectivement 33.3, 41.7 et 41.2% des patients. Il n'y avait aucune différence postopératoire en ce qui concerne les tests de performance ou les tests de laboratoire. En conclusion, bien que la voie intrathoracique soit la meilleure en ce qui concerne l'alimentation, il n'y avait aucune différence quant à la qualité de vie pour les trois techniques.La qualité de vie s'est amélioré progrèssivement chez tous les patients quelle que soit la technique employée s'il n'avait pas de récidive.

     

Preoperative hyperthermo-chemo-radiotherapy of carcinoma of the esophagus

Hyperthermia is particularly effective for the treatment of clinical carcinoma when applied concomitantly with radiation and chemotherapy. However, there are certain difficulties when hyperthermia is to be applied to a deeply located lesion and the approach to heating only a deep portion of the body and measurement of the exact temperature in these deep areas has remained a problem in therapeutics. We devised an antenna for radio frequency (RF). This is easily inserted into the esophagus, and carcinoma of the esophagus is properly warmed and the exact temperature is monitored. We have prescribed preoperative hyperthermo-chemo-radiotherapy for 31 patients with carcinoma of the esophagus, and we examined the histological findings of the resected specimens. The findings were compared with data on 108 patients treated with preoperative irradiation only. The preoperative hyperthermo-chemo-radiotherapy increased the rate of "markedly effective" in the resected tissue comparing with the findings in case of irradiation only. Thus, preoperative hyperthermo-chemo-radiotherapy is the recommended treatment for patients with carcinoma of the esophagus.