Carcinoma-associated fibroblasts (CAFs) influence tumor initiation, progression, and metastasis within the tumor-associated stroma. This suggests that CAFs would be a potential target for tumor therapy. Here we found that Hydrogen peroxide-inducible clone-5 (Hic-5), also named transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was strongly induced in CAFs found in human colorectal cancer. To investigate the role of Hic-5 in CAFs, we isolated CAFs and the control counterpart normal fibroblasts (NFs) from human colorectal cancer and non-cancerous regions, respectively. Hic-5 was highly expressed in isolated human CAFs and strongly induced in NFs in culture by the supernatant from cultured colorectal cancer cells as well as cytokines such as TGF-β, IL-1β and stromal cell-derived factor 1 (SDF-1/CXCL12). Furthermore, tumor growth was inhibited in a co-culture assay with Hic-5 knockdown fibroblasts compared with control fibroblasts. To clarify the function and significance of Hic-5 in colorectal cancer in vivo, we utilized a mouse model of azoxymethane (AOM)-induced colorectal cancer using Hic-5-deficient mice. Lack of Hic-5 in CAFs completely prevented AOM-induced colorectal cancer development in the colon tissues of mice. Mechanistic investigation revealed that Hic-5 promoted the expression of lysyl oxidase and collagen I in human control counterpart fibroblasts. Taken together, these results demonstrate that Hic-5 in CAFs is responsible for orchestrating or generating a tumor-promoting stroma.
Objectives: Aneurysm shrinkage after EVAR is the strong factor of favorable outcomes after endovascular abdominal aortic aneurysm repair (EVAR), and type II endoleaks is the risk factor of no aneurysm shrinkage or aneurysm enlargement in the long term. In this study, we evaluate the aortic side branches relate to early postoperative type II endoleak, and performed coil embolization for those vessels for prevention of type II endoleak.Methods: Patency and diameter of aortic side branches including inferior mesenteric artery (IMA) and lumbar artery (LA) were evaluated in 56 consecutive patients with abdominal aortic aneurysm who were scheduled for EVAR. Coil embolization with Interlock was performed in 24 patients during EVAR for all patent IMA and LA with maximal diameter more than 2.0 mm. Computed tomography was performed one week after EVAR for evaluation of endoleak.Results: In patients with IMA more than 2.5 mm in diameter, the frequency of type II endoleak was approximately 90% regardless of the number of patent LA. In case with patent IMA less than 2.5 mm or with 2 or more patent LA larger than 2.0 mm, the frequency of type II endoleak was 46 to 67%. Coil embolization for IMA was successfully performed in 15/16 patients (94%). Coil embolization of LA was performed for patent LA larger than 2.0 mm and 29 out of 45 LA (64%) were successfully occluded. There was no perioperative complication associated with coil embolization. The frequency of type II endoleak was significantly lower in patients with coil embolization than those without coil embolization (4.2% vs 58.9%, p<0.0001).Conclusion: Patent IMA and LA in diameter larger than 2.0 mm were associated with type II endoleak one week after EVAR, and coil embolization with Interlock during EVAR is safe and effective procedure to prevent type II endoleak. (This is a translation of Jpn J Vasc Surg 2016; 25: 321–328.)
Regression analysis was performed using 53 clinical variables. Female gender, renal insufficiency, concomitant coronary artery bypass grafting, and preoperative right ventricular end-diastolic pressure > 20 mm Hg were found to be predictors of poor survival. At follow-up, improved functional status was noted in 88% of patients. Subtotal pericardiectomy can be performed on cardiopulmonary bypass with low mortality and good long-term survival.
Mitral valve repair is preferred to replacement in infective endocarditis, but in the active phase, it often requires extensive debridement of infected tissue and complex reconstruction. We investigated 22 consecutive native mitral valve operations during active-phase infective endocarditis. The time from initiation of medical treatment to operation was 16.8 ± 16.4 days. Mitral valve repair was performed in 15 (68.2%) patients, using prosthetic annuloplasty in 14, an autologous pericardial patch in 11, and artificial chordal replacement in 9. Hospital mortality was 9.1% (2 patients), due to subarachnoid hemorrhage and pneumonia. One patient died 26 months after valve replacement due to congestive heart failure. The postoperative left ventricular end-diastolic dimension was significantly smaller (45.7 ± 5.6 vs. 53.3 ± 10.2 mm) and ejection fraction was significantly higher (57.0% ± 14.7% vs. 40.1% ± 8.2%) in patients who underwent valve repair compared to those who had valve replacement. Mitral regurgitation requiring reoperation occurred in 3 patients during follow-up. Mitral valve repair is feasible in active-phase infective endocarditis, and results in improved regression of left ventricular dimensions compared to valve replacement. However, complex mitral valve repair with extensive leaflet resection may not have long-term durability.
Aorto-esophageal fistula (AEF) is a rare complication of esophageal carcinoma. Left untreated, it may be lethal due to massive upper gastrointestinal bleeding, while open thoracic surgery is associated with high operative mortality and morbidity. In contrast, thoracic endovascular aortic repair (TEVAR) for AEF is less invasive than open thoracic surgery. Here, we report 3 successful cases of AEF with esophageal carcinoma treated using TEVAR under local anesthesia in the emergent or urgent phase. General condition of all the patients was dramatically improved, but 1 patient with exsanguinations developed infection of the implanted stent-graft and died due to sepsis. The other 2 patients were treated before esophageal bleeding and remained alive for 1 year without infection. The TEVAR should be considered as early as possible in patients with advanced esophageal carcinoma receiving radiation or chemotherapy who develop early signs of AEF such as symptoms of chest discomfort or descending aortic irregularity on computed tomography scan.
Mycotic embolism in patients with infective endocarditis is not uncommon, however, mycotic aneurysm of a coronary artery is very rare. We report the case of a 62-year-old woman with mitral valve endocarditis complicated by mycotic aneurysm of the right coronary artery. Mitral valve replacement and resection of the mycotic aneurysm with coronary artery bypass were performed.
Even without additional sources of pulmonary blood flow, several preoperative factors, including younger age and severe ventricular volume overload, predicted a decrease in the arterial oxygen saturation early after bidirectional cavopulmonary shunting. This, in turn, predicted poor outcome during 2 years of follow-up.
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