Reversion-inducing-cysteine-rich protein with Kazal motif is involved in intimal hyperplasia in carotid arteries: a new insight in the prevention of restenosis after vascular angioplasty.

BACKGROUND: Overexpression of matrix metalloproteinase (MMP) has been implicated in the incidence of restenosis after vascular angioplasty. Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a membrane-anchored glycoprotein that negatively regulates the activity of MMPs, such as MMP-9 and MMP-2, which play a key role in the angiogenesis during tumor growth. This study was designed to investigate the potential association between RECK and restenosis after vascular angioplasty. METHODS: Balloon-injured rabbit carotid arterial models were established. Arterial morphology was assessed by hematoxylin-eosin staining. The area of intimal hyperplasia was measured using image microscopy and image analyzer. The messenger RNA (mRNA) expression levels of RECK, MMP-9, and MMP-2 were detected using reverse transcription-polymerase chain reaction (RT-PCR) at 7, 14, and 21 days. Vascular smooth muscle cells (VSMCs) were transfected with RECK small interfering RNA (siRNA). VSMC proliferation rate was detected by MTT assay at 24, 48 and 72 hr. The protein expression of RECK, MMP-9, and MMP-2 was determined by Western blot. RESULTS: MMP-2 and MMP-9 in carotid artery of rats were significantly overexpressed in the injured-artery group, compared with unmanipulated control and contralateral uninjured groups (P < 0.05). With the time of the injury extended, MMP-2 and MMP-9 mRNA levels gradually increased. RECK showed a marked peak of mRNA level at 7 days after injury, compared with unmanipulated control and contralateral uninjured groups (P < 0.001). However, the increasing trend gradually decreased at 14 days after the balloon surgery. RECK mRNA was still detectable at 21 days postoperatively, but the expression level of RECK mRNA in injured and contralateral uninjured groups was significantly lower than that in unmanipulated control group (P < 0.001). The expression level of RECK protein in VSMCs in transfected group was significantly lower compared with that in untransfected group, whereas the expression of MMP-2 and MMP-9 proteins in transfected group was significantly higher compared with that in untransfected group. Over the extension of transfection time, the proliferation of VSMCs in transfected group was increased gradually, compared with negative and blank plasmid controls (P < 0.05). CONCLUSIONS: RECK, as siRNA-mediated RECK silencing regulation of MMP-9 and MMP-2, plays an important role in intimal hyperplasia, which provides a new target for prevention and treatment of restenosis after vascular angioplasty.

Application of protective stents in endovascular repair of acute complicated Stanford type B aortic dissections.

PURPOSE: To describe the use of protective stents in the endovascular repair of acute complicated Stanford type B aortic dissections. METHODS: From 2009 to 2011, 33 patients (27 men; mean age 47 years, range 31-73) with acute complicated Stanford type B aortic dissection underwent thoracic endovascular aortic repair (TEVAR) assisted by protective stents. In all cases, the proximal and distal landing zones differed in size by >5 mm, and the primary entry tear was in the proximal descending aorta. A bare self-expanding stent (protective stent) was deployed initially at the intended distal landing site of the primary stent-graft in the true lumen. The intention was that the bare stent would prevent excessive dilation of the distal end of the stent-graft in the vicinity of the entry tear, thus avoiding intimal rupture. RESULTS: Successful stent deployment and sealing of the entry tear was achieved in all patients. The median diameter and length of the protective bare stents was 20.3 mm (range 18-24) and 72.7 mm (range 60-80), respectively, while the corresponding dimensions of the covered stent-grafts were 32.8 mm (range 26-40) and 157.4 mm (range 120-200 mm), respectively. There was no stent twisting, migration, of rupture of the false or true lumen. Computed tomography 1 week postoperatively demonstrated closure of the primary entry tear with thrombosis of the false lumen in all cases. No patients were lost to follow-up, which has ranged from 3 months to 3 years. No late endoleaks or stent complications, such as angulation, dislodgment, persistent leaks, branch obstruction, or stent-graft migration, have been observed, and there has been no chronic progressive true or false lumen dilatation, recurrences, or deaths. CONCLUSION: Adjunctive use of a protective stent when treating acute Stanford type B aortic dissections in which the diameters of the proximal and distal landing zones differ by >5 mm is feasible and safe and provides good short-term outcomes.

Perioperative approach in the surgical management of carotid body tumors.

BACKGROUND: Now, surgical resection still remains the gold standard for the treatment of carotid body tumors (CBTs). Although advances in surgical techniques and the introduction of sensitive imaging modalities have significantly reduced mortality, the incidence of perioperative neurovascular complications, especially cranial nerve deficit and intraoperative hemorrhage, remains considerable. To solve these problems, preoperative embolization has been suggested; the reported benefits of preoperative embolization performed <48 hours before surgery include a reduction in tumor size, decreased blood loss, and improved visualization, theoretically reducing neurologic morbidity by lessening the risk of stroke and damage to cranial nerves. The purpose of this study was to review our experience in the surgical management of CBTs with preoperative embolization and evaluate the outcomes and complications according to the Shamblin classification. METHODS: Thirty-two patients who had been diagnosed with and surgically treated for CBTs were enrolled from January 2005 till July 2010. All perioperative scans were evaluated by computed tomography angiography. We reviewed patient demographics, radiographic findings, and surgical outcomes collected from medical records. RESULTS: Thirty-two patients underwent surgical excision without mortality. Angiography with selective preoperative tumor embolization was performed on 21 patients. The median blood loss, operation time, and hospital stay for these patients were significantly reduced compared with those without embolization. There were no recurrences or delayed complications at the median follow-up of 20 months. CONCLUSION: Embolization as an adjunctive tool was beneficial for CBT surgery outcomes. Embolization should only be undertaken in those vessels that can be subselectively catheterized and determined not to allow free reflux of contrast medium into the internal carotid artery. Tumor embolization was performed on patients with Cook detachable coils, which are highly effective for supply artery closure if properly selected, and complications can be minimized by proper selection and positioning of the coil. Operation within 48 hours after embolization is recommended to minimize revascularization edema or a local inflammatory response.

A case of cystic duct drainage into the left intrahepatic duct and the importance of laparoscopic fundus-first cholecystectomy for prevention of bile duct injury.

The laparoscopic cholecystectomy is the gold standard for the treatment of cholecystolithiasis, although it has been reported that the incidence of bile duct injury is higher for this method than for conventional open surgery. These injuries are mainly attributable to a misunderstanding of the biliary tract anatomy owing to severe cholecystitis, large impacted stones, and anatomic variations. In this paper, we report on the successful treatment of a 59-year-old male patient with cholecystolithiasis accompanied with extremely unusual biliary junction, in which the cystic duct drained into the left hepatic duct while using the laparoscopic fundus-first-cholecystectomy approach (i.e., the doom down technique) without any serious intraoperative complications. If the doom-down technique was not indicated in this particular case, the authors believe that a careless division of the cystic duct may have resulted in operative morbidity.

[Multicenter comparative study of the recurrence-inhibitory effect of oral fluoropyrimidine drugs in patients with colorectal cancer following curative resection].

HCFU and UFT were reported effective in adjuvant chemotherapy for colorectal cancer. This investigation was planned as a randomized study to compare the usefulness of combination therapies with mitomycin C (MMC)+HCFU and MMC+UFT as postoperative adjuvant chemotherapy in patients with colorectal cancer following curative resection, in terms of survival rate, recurrence rate, and adverse drug reactions. A total of 501 patients consisting of 252 patients with stage III/IV colon cancer (Colorectal Cancer Handling Rules, 4th Ed.) for which macroscopic curative resection was possible and 249 patients with stage II/III/IV rectal cancer (ibid, 4th Ed.) were registered from 40 participating institutions. The patients were randomly allocated to two groups with colon cancer and rectal cancer employed as stratification factors. Beginning on Day 14 after surgery, HCFU at 300 mg/day was administered to one group and UFT at 300 mg/day or 400 mg/day to another group, both orally and daily for one year. MMC 6 mg/m2 was administered intravenously to both groups on the day of surgery and the day following. Among the 501 patients, 496 patients (99%) were eligible. The 5-year survival rates were 77.1% for the MMC+ HCFU group and 79.2% for the MMC+UFT group, with the 5-year recurrence-free survival rates were 76.1% and 72.9%, respectively, neither showing a significant difference between the groups. Adverse drug reactions appeared in 23% of patients in the MMC+HCFU group and in 19% in the MMC+UFT group, with no serious reactions. One year after surgery the administration completion rates were good, at 82% for the MMC+HCFU group and 83% for the MMC+UFT group. No clear difference in effectiveness was noted between MMC+HCFU therapy and MMC+UFT therapy as postoperative adjuvant chemotherapy for colorectal cancer. The administration completion rates were good, and no serious adverse drug reactions were observed for either therapy. It was thus considered that both therapies could be administered safely, and both were useful as postoperative adjuvant chemotherapies for colorectal cancer. It is considered necessary to compare them with standard therapies in Western countries in the future.

[Expression of Fas and induction of apoptosis by anti-Fas monoclonal antibody in human bile duct carcinoma cells, and enhancement of induction of apoptosis by IFN-gamma].

We investigated the expression of Fas, the induction of apoptosis by anti-Fas monoclonal antibody CH-11, and the effect of IFN-gamma on the induction of apoptosis in human bile duct carcinoma cells HuCCT1 and HuH28. Fas was expressed in 21.7% and 30.9% of HuCCT1 and HuH28 cells, respectively. Pretreatment with IFN-gamma increased the Fas expression by 17.6% in HuCCT1 cells. However, IFN-gamma did not affect the expression of Fas in HuH28 cells. In HuCCT1 and HuH28 cells treated with CH-11, the peak corresponding to that of positive control cells was detected with the TUNEL method by FCM. The condensation and fragmentation of the nucleus, and the apoptotic body were observed as morphological changes specific to apoptosis. CH-11 dose-dependently reduced HuCCT1 and HuH28 cell counts by up to 16.4% and 71.7%, respectively on day 3. Interferon-gamma attenuated the reduction of HuCCT1 cell counts by 12.8% on day 3. However, IFN-gamma had no effect on HuH28 cell counts. These results suggest that Fas was expressed, apoptosis was induced by CH-11 and the induction of apoptosis was enhanced by IFN-gamma in human bile duct carcinoma cells.

[Evaluation of the diagnostic efficacy of SPIO enhanced MRI in patients with focal hepatic lesions--comparison with CECT and CTAP].

The aim of this study was to compare the diagnostic efficacy of superparamagnetic iron oxide (SPIO)-enhanced MRI for the detection and diagnostic accuracy of focal liver lesions with helical contrast enhanced CT (CECT) and CT during arterial portography (CTAP). Thirty-nine patients (25 men and 14 women, mean age 63.5 years) were examined by SPIO-MRI and triple-phase CECT. Eleven of them were also examined by CTAP. There were a total of 96 confirmed focal hepatic lesions, 61 metastatic cancers in 18 patients and 35 hepatocellular carcinomas (HCCs) in 21 patients. Final diagnosis was established by operation in 25 cases, by biopsy in 7 cases, and by progression of disease on follow-up examination in the other 7 cases. The sensitivity of SPIO-MRI for HCC detection was almost equal to CECT, but that of SPIO-MRI for metastatic cancer detection, especially cancers smaller than 1 cm in size, was significantly superior to CECT. The sensitivity of SPIO-MRI for both HCC and metastatic cancer detection was almost equal to that of CTAP, but the specificity of SPIO-MRI for detection of both lesions was significantly superior to that of CTAP because CTAP produced a higher incidence of false-positive findings. In conclusion, SPIO-MRI could take the place of CTAP as a non-invasive excellent modality to determine the distribution of hepatic lesions preoperatively. SPIO-MRI could also be a useful modality to follow liver metastasis postoperatively in patients with advanced digestive cancers.

Ruptured hepatic subcapsular hematoma following laparoscopic cholecystectomy: report of a case.

Laparoscopic cholecystectomy is now a standard procedure for cholecystolithiasis because of its minimally invasive nature compared to the conventional method. However, severe complications that have never been seen for open surgery have also been reported. Here, we report the case of a 28-year-old woman who underwent laparoscopic cholecystectomy and then developed a ruptured subcapsular hematoma. On postoperative day 1, she developed shock, and postoperative bleeding was suspected. During re-operation, a ruptured subcapsular hematoma of the whole right lobe of the liver with active bleeding was found, and hemostasis was achieved. In this case, it was assumed that the rupture of the subcapsular hematoma was due to compression of the liver by the clamp for retrieving the spilled gallstones during the first operation and perioperative administration of nonsteroidal anti-inflammatory drugs.

A mechanism for antibody-mediated outside-in activation of LFA-1.

MEM83 is an inserted domain (I-domain)-specific antibody that up-regulates the interaction of LFA-1 with ICAM-1 through an outside-in activation mechanism. We demonstrate here that there is no change in the affinity of the MEM83 antibody for the I-domain in either its low (wild-type) or high affinity form and that MEM83 does not enhance the binding of the wild-type I-domain to ICAM-1. Furthermore, we show that the antibody acts as an activating agent to induce LFA-1/ICAM-1-dependent homotypic cell aggregation only as an IgG, but not as a Fab fragment. On the basis of these data, we propose an avidity-based mechanism that requires no direct activation of the LFA-1 I-domain by the binding of the antibody; rather, activation is enhanced when there is an interaction with both arms of the IgG. A molecular model of the antibody interaction with LFA-1 illustrates the symmetry and accessibility of the two MEM83 epitopes across the LFA-1/ICAM-1 heterotetramer. We hypothesize that MEM83 stabilizes adjacent LFA-1 molecules in their active form by the free energy that is gained from the binding of the I-domains to each arm of the IgG. This leads to stabilization of the open state of the integrin and outside-in signaling. Our model supports a mechanism in which both affinity and avidity regulation are required in the activation of LFA-1.

Ceramide induces apoptosis in human lung adenocarcinoma A549 cells through mitogen-activated protein kinases.

AIM: To provide experimental data for further research on the signal transduction of apoptosis in lung adenocarcinoma cells, we examined the effects of exogenous C2-ceramide administration on several members of the mitogen-activated protein kinase (MAPK) superfamily and caspase-3 in A549 cells. METHODS: Cell viability and apoptosis were analyzed by cell counting kit-8 assay and flow cytometry. Various MAPK and caspase-3 proteins were detected by Western blotting. RESULTS: C2-ceramide selectively altered the phosphorylation state of members of the MAPK superfamily, causing hyperphosphorylation of mitogen-activated protein kinase kinase (MEK)1/2 and the p38 MAPK, but not affecting the phosphorylation of extracellular signal-regulated kinase 1/2 and the c-Jun N-terminal kinase. SB-203580 (a p38 MAPK inhibitor) and p38 siRNA, but not U0126 (a MEK inhibitor), partially rescued cell death induced by C2-ceramide. C2-ceramide promoted the activation of caspase-3. CONCLUSION: Exogenous C2-ceramide induced apoptosis in human lung adenocarcinoma A549 cells. The activation of MAPK and caspase-3 were involved in the mechanisms of C2-ceramide-induced apoptosis in A549 cells.