Initial and midterm results for repair of aortic diseases with handmade stent grafts.

BACKGROUND: The purpose of this study was to determine the initial and midterm results for repair of thoracic and abdominal aortic diseases using handmade stent-grafts (SGs). METHODS AND RESULTS: Between 1999 and 2004, 41 consecutive patients (31 patients with thoracic and 10 patients with abdominal aortic disease) underwent endovascular stent-graft repair using handmade SGs. The follow-up averaged 24.8+/-17.6 months. The technical and initial clinical success rates were 82.9% (34/41) and 80.5% (33/41), respectively. Primary type I or III endoleaks occurred in 12.2% (5/41) of the patients. The hospital mortality rate was 4.9% (2/41). Persistent type I or III endoleaks occurred in 9.8% (4/41) and SG migrations occurred in 4.9% (2/41) of the patients. Open surgical conversion was undertaken in 12.2% (5/41) of the patients because of an endoleak and/or migration. The mean change observed in the aneurysm diameter was -6.2+/-10.5 mm, and shrinkage in the diameter occurred in 51.4% (18/35) of the cases. There was 1 patient death because of aneurysm rupture. Neither stent fracture nor graft hole was observed. The overall clinical success rate during follow-up was 78.0% (32/41). CONCLUSION: The initial and midterm results obtained after repair of the aortic diseases using handmade SGs were considered to be satisfactory. More surgical experience and long-term patient follow-up are both required to further reassess the effect of this treatment.     

Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice

The present study was designed to determine whether tumor induction by 3-methylcholanthrene (MC), a carcinogenic hydrocarbon, can be inhibited by oral administration of Lactobacillus casei strain Shirota (LC). C3H/HeN mice were divided into four groups and assigned to the following treatments: treated with MC and given control or LC-containing diet; treated with vehicle only and given control or LC-containing diet. MC (1 mg) was injected intradermally at 7 weeks of age and the tumor incidence was monitored; LC was mixed into a diet at a concentration of 0.05% (w/w) and the diet was fed from the day of MC injection throughout the study. Spleen cells were analyzed for the immune parameters at 12 and 16 weeks after the MC injection. Oral feeding of mice with LC reduced tumor incidence (P < 0.05). MC treatment lowered the in vitro response to concanavalin A (Con A) of spleen cells, the secretion of interleukin-2 in spleen cell culture after stimulation of the cells with Con A and the proportions of CD3⁺, CD4⁺ and CD8⁺ splenic cells. However, the analysis of the spleen cells obtained from the mice treated with MC and given the LC-containing diet revealed that these disrupted host immune parameters were maintained at the level of normal controls. These results suggest that oral feeding of mice with LC inhibits MC-induced tumorigenesis by modulating the disrupted host immune responses during MC carcinogenesis. Received: 14 April 1999     

Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities in macrophages through Toll-like receptor 2

Lactobacilli are nonpathogenic gram-positive inhabitants of microflora. At least some Lactobacillus strains have been postulated to have health beneficial effects, such as the stimulation of the immune system. Here we examined the stimulatory effects of lactobacilli on mouse immune cells. All six heat-killed Lactobacillus strains examined induced the secretion of tumor necrosis factor alpha (TNF-alpha) from mouse splenic mononuclear cells, albeit to various degrees. When fractionated subcellular fractions of Lactobacillus casei were tested for NF-kappaB activation and TNF-alpha production in RAW264.7, a mouse macrophage cell line, the activity was found to be as follows: protoplast > cell wall > polysaccharide-peptidoglycan complex. Both crude extracts and purified lipoteichoic acids (LTAs) from two Lactobacillus strains, L. casei and L. fermentum, significantly induced TNF-alpha secretion from RAW264.7 cells and splenocytes of C57BL/6, C3H/HeN, and C3H/HeJ mice but not from splenocytes of C57BL/6 TLR2(-/-) mice. Lactobacillus LTA induced activation of c-Jun N-terminal kinase activation in RAW264.7 cells. Furthermore, in HEK293T cells transected with a combination of CD14 and Toll-like receptor 2 (TLR2), NF-kappaB was activated in response to Lactobacillus LTA. Taken together, these data suggest that LTAs from lactobacilli elicit proinflammatory activities through TLR2.     

Role of colony-stimulating activity in antitumor activity of Lactobacillus casei in mice

Wide-ranging differences were observed between the antitumor activities of 23 lactobacilli (13 species; 23 strains) and their capacities to elevate the level of serum colony-stimulating activity (CSA) by intraperitoneal administration in mice, and a good correlation existed between the two activities. The mechanism of enhanced production of CSA by administration of Lactobacillus casei YIT 9018 (LC 9018), one of the bacteria that had the strongest activities, and the role of CSA in antitumor activity of LC 9018 were studied. Colony-stimulating activity in the washing fluid from the peritoneal cavity of mice that had been administered LC 9018 intraperitoneally was elevated at 3 to 24 h after the injection, and CSA was also detected at elevated levels in the serum of the mice 6 to 12 h after injection. The cells responsible for the production of CSA after stimulation with LC 9018 seem to be the resident macrophages at the site of administration, because the resident macrophages of mice lavaged 1 h after an intraperitoneal administration of LC 9018 released CSA when they were cultured in vitro. Moreover, resident peritoneal macrophages of normal mice cultured with LC 9018 in vitro also produced CSA. Similar results were obtained with athymic nude mice, and the CSA-inducing activity of LC 9018 was diminished in the mice pretreated with carrageenan, which is selectively toxic to mature macrophages. Bone marrow cells matured to macrophages and polymorphonuclear cells by culture with the CSA induced by LC 9018 for 7 days. These matured macrophages showed strong antitumor activity both in vivo and in vitro. These results suggest that CSA plays important roles in the antitumor activity of LC 9018: it enhances not only the multiplication of committed precursor cells for macrophages and polymorphonuclear cells, but also the functional maturation of the precursor cells for macrophages which serve as potent effectors for tumor cells.     

Augmentation of antimetastatic effect on Lewis lung carcinoma (3LL) in C57BL/6 mice by priming with Lactobacillus casei

The augmentation of the antimetastatic effect of heat-killed cells of Lactobacillus casei YIT9018 (LC 9018) on Lewis lung carcinoma (3LL) in C57BL/6 mice by presensitization (priming) with LC 9018 was examined. Intralesional injection of LC 9018 into 3LL-bearing mice inhibited both the growth of the primary tumors and the formation of lung metastases, and this effect was significantly augmented by subcutaneous injection of LC 9018 before the tumor inoculation. In the LC 9018-primed mice, intraperitoneal administration of LC 9018 into syngeneic hosts after priming induced a high level of interleukin-2 (IL-2) and interferon- (IFN-) in the peritoneal cavity. At this time, T cells of the spleen cells from the LC 9018-primed mice proliferated and produced IL-2 when co-cultured with LC 9018 as antigen in vitro. Also, the phenotype of these T cells was found to be L3T4⁺ and Ly-2.2^– T cells by analysis by flow cytometry. These results suggest that LC 9018-reactive helper T (T_h) cells were induced by the priming and subsequent challenge with LC 9018, and that IL-2 or IFN-, which was produced by the activated LC 9018-reactive T_h cells, augmented a host immune response resulting the antitumor activity.     

The role of tumor necrosis factor (TNF)-α in the antitumor effect of intrapleural injection of Lactobacillus casei strain Shirota in mice

The involvement of several cytokines in the antitumor effect induced by intrapleural (i.pl.) injection of heat-killed cells of Lactobacillus casei strain Shirota (LC 9018) in mice was investigated. Injection of LC 9018 i.pl. into Meth A fibrosarcoma (Meth A)-bearing mice not only significantly prolonged the survival of the mice, but also effectively inhibited the accumulation of malignant pleural fluid in the thoracic cavity. In the thoracic cavity of tumor-bearing mice treated with LC 9018, we observed large amounts of several cytokines including interleukin (IL)-1β, interferon (IFN)-γ, IL-12 and tumor necrosis factor (TNF)-α. Both anti-IFN-γ and anti-IL-12 monoclonal antibody (mAb) treatments partially diminished the antitumor activity of LC 9018 in vivo, while the treatment of anti-IL-1β mAb did not influence the survival of the mice. However, anti-TNF-α mAb treatment completely abolished the antitumor effect of LC 9018 in vivo, suggesting that in this model LC 9018 has a survival-prolonging effect involving certain cytokines. Moreover, i.pl. injection of mouse recombinant TNF-α into Meth A-bearing mice pretreated with anti-TNF-α mAb partially restored the survival-enhancing effect of LC 9018. These results led us to conclude that TNF-α induced by i.pl. injection of LC 9018 plays an important role in the antitumor effect of LC 9018 in vivo. Received: 22 February 1999     

Activity of cytotoxic agents against clear cell carcinoma of the ovary which is intrinsically platinum-refractory

The aim of the present study was to evaluate cytotoxic agents active for clear cell carcinoma of the ovary (OCCA) which is intrinsically platinum-resistant. We first conducted in vitro chemosensitivity tests assessing antitumor activities of Various agents against OCCA using two cell lines (HAC-2 and KK) established from ascites of patients with pure OCCA. The most potent single agent was SN-38 (active substance of CPT-11 in vivo) in both cell lines. The second most potent agent was mitomycin-C (MMC) followed by doxorubicin (DOX) in HAC-2 and DOX followed by MMC in KK, respectively. In vivo chemosensitivity test of agents on HAC-2 transplanted into BALB/C nude mice demonstrated that MMC was most potent, followed by DOX and CPT-11. Moreover, a combination of CPT-11 and MMC exhibited the highest anti-tumor activity in this animal model. Cisplatin, etoposide, and paclitaxel were found to be ineffective in either the in vitro or in vivo experimental system. Clinical trial with a combination of MMC and CPT-11 are warranted in patients with OCCA.     

Clinical outcome after cardiac operations in patients with cirrhosis

BACKGROUND: To evaluate the clinical outcome after cardiac operations in patients with cirrhosis, a retrospective study was undertaken. METHODS: Between 1989 and 2003, 18 patients with cirrhosis who underwent cardiac operations were identified. Their preoperative status and postoperative clinical results were assessed. RESULTS: Ten patients were classified as having Child-Pugh class A cirrhosis, 7 as having class B cirrhosis, and 1 as having class C cirrhosis. Fifteen of 18 patients underwent cardiac surgery using cardiopulmonary bypass, and the remaining 3 patients with class B cirrhosis received coronary artery bypass grafting without cardiopulmonary bypass. In patients undergoing cardiopulmonary bypass, 60% of those with class A cirrhosis and 100% of those with class B cirrhosis and class C cirrhosis had postoperative major complications, including infection, respiratory failure, renal failure, bleeding, and gastrointestinal disorder. One of 3 patients (33%) with class B cirrhosis undergoing coronary artery bypass grafting without cardiopulmonary bypass had major complications. The overall postoperative mortality rate was 17%. Hospital mortality of patients with class A cirrhosis, class B cirrhosis, and class C cirrhosis undergoing cardiopulmonary bypass was 0%, 50%, and 100%, respectively. None of 3 patients with class B cirrhosis undergoing coronary artery bypass grafting without cardiopulmonary bypass died in this study. CONCLUSIONS: Although the incidence of major complications was high, patients with Child-Pugh class A cirrhosis tolerated cardiac surgery satisfactorily. Patients with more advanced cirrhosis, however, may not be suitable for elective cardiac operations with cardiopulmonary bypass. Although our results are not conclusive, coronary artery bypass grafting without cardiopulmonary bypass can be an alternative therapeutic strategy for patients with advanced cirrhosis requiring surgical revascularization.