Splenic Rupture in Children With Portal Hypertension.

INTRODUCTION: Massive splenomegaly from portal hypertension (PHTN) in children raises the specter of splenic rupture; however, the incidence, etiology, and risk of rupture have not been studied, nor have existing practices to reduce risk. We therefore performed an international survey to describe the splenic rupture cases in PHTN and to describe the existing empirical practice among hepatologists. METHODS: A questionnaire was constructed to elicit cases of splenic rupture and collect hepatologists' common practices for prevention of splenic rupture. Pediatric hepatologists working in selected tertiary academic centers in the United States, Canada, and the United Kingdom were contacted. RESULTS: Hepatologists from 30 of 35 centers who met the inclusion criteria replied to the survey. Thirteen cases of splenic rupture were described of which 11 resulted from trauma. In the opinion of the practitioners, high-risk activities were football, hockey, and wrestling. Sixty-one percent recommended total restriction from high-risk activities. Seventy-four percent stated that platelet count had no effect on this decision and 61% advised a spleen guard for certain activities. CONCLUSIONS: Splenic rupture in patients with PHTN and splenomegaly seems to be rare. The reported splenic rupture cases were mostly related to falling (and not to participation in sports). There was general agreement among hepatologists about restricting high impact sports. There was variation in recommendations regarding the use of a spleen guard. The authors recommend use of spleen guards in children with splenomegaly from PHTN for physical activities with risk of fall or blunt abdominal trauma.

Totally percutaneous versus surgical cut-down femoral artery access for elective bifurcated abdominal endovascular aneurysm repair.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are a vascular condition with significant risk attached, particularly if they rupture. It is, therefore, critical to identify and repair these as an elective procedure before they rupture and require emergency surgery. Repair has traditionally been an open surgical technique that required a large incision across the abdomen. Endovascular abdominal aortic aneurysm repairs (EVARs) are now a common alternative. In this procedure, the common femoral artery is exposed via a cut-down approach and a graft introduced to the aneurysm in this way. This review examines a totally percutaneous approach to EVAR. This technique gives a minimally invasive approach to femoral artery access that may reduce groin wound complication rates and improve recovery time. The technique may, however, be less applicable in people with, for example, groin scarring or arterial calcification. This is an update of the review first published in 2014. OBJECTIVES: This review aims to compare the clinical outcomes of percutaneous access with surgical cut-down femoral artery access in elective bifurcated abdominal endovascular aneurysm repair (EVAR). SEARCH METHODS: For this update the Cochrane Vascular Information Specialist (CIS) searched their Specialised Register (last searched October 2016) and CENTRAL (2016, Issue 9). We also searched clinical trials registries and checked the reference lists of relevant retrieved articles. SELECTION CRITERIA: We considered only randomised controlled trials. The primary intervention was a totally percutaneous endovascular repair. We considered all device types. We compared this against surgical cut-down femoral artery access endovascular repair. We only considered studies investigating elective repairs. We excluded studies reporting emergency surgery for a ruptured abdominal aortic aneurysm and those reporting aorto-uni-iliac repairs. DATA COLLECTION AND ANALYSIS: Two review authors independently collected all data. Owing to the small number of trials identified we did not conduct any formal sensitivity analysis. Heterogeneity was not significant for any outcome. MAIN RESULTS: Two studies with a total of 181 participants met the inclusion criteria, 116 undergoing the percutaneous technique and 65 treated by cut-down femoral artery access. One study had a small sample size and did not adequately report method of randomisation, allocation concealment or pre-selected outcomes. The second study was a larger study with few sources of bias and good methodology.We observed no significant difference in mortality between groups, with only one mortality occurring overall, in the totally percutaneous group (risk ratio (RR) 1.50; 95% confidence interval (CI) 0.06 to 36.18; 181 participants; moderate-quality evidence). Only one study reported aneurysm exclusion. In this study we observed only one failure of aneurysm exclusion in the surgical cut-down femoral artery access group (RR 0.17, 95% CI 0.01 to 4.02; 151 participants; moderate-quality evidence). No wound infections occurred in the cut-down femoral artery access group or the percutaneous group across either study (moderate-quality evidence).There was no difference in major complication rate between cut-down femoral artery access and percutaneous groups (RR 0.91, 95% CI 0.20 to 1.68; 181 participants; moderate-quality evidence); or in bleeding complications and haematoma (RR 0.94, 95% CI 0.31 to 2.82; 181 participants; high-quality evidence).Only one study reported long-term complication rates at six months, with no differences between the percutaneous and cut-down femoral artery access group (RR 1.03, 95% CI 0.34 to 3.15; 134 participants; moderate-quality evidence).We detected differences in surgery time, with percutaneous approach being significantly faster than cut-down femoral artery access (mean difference (MD) -31.46 minutes; 95% CI -47.51 minutes to -15.42 minutes; 181 participants; moderate-quality evidence). Only one study reported duration of ITU (intensive treatment unit) and hospital stay, with no difference found between groups. AUTHORS' CONCLUSIONS: This review shows moderate-quality evidence of no difference between the percutaneous approach compared with cut-down femoral artery access group for short-term mortality, aneurysm exclusion, major complications, wound infection and long-term (six month) complications, and high-quality evidence for no difference in bleeding complications and haematoma. There was a difference in operating time, with moderate-quality evidence showing that the percutaneous approach was faster than the cut-down femoral artery access technique. We downgraded the quality of the evidence to moderate as a result of the limited number of studies, low event numbers and imprecision. As the number of included studies were limited, further research into this technique would be beneficial. The search identified one ongoing study, which may provide an improved evidence base in the future.

Is there still a place for Achilles tendon lengthening?

Patients with diabetes and ankle equinus are at particularly high risk for forefoot ulceration because of the development of high forefoot pressures. Stiffness in the triceps surae muscles and tendons are thought to be largely responsible for equinus in patients with diabetes and underpins the surgical rationale for Achilles tendon lengthening (ATL) procedures to alleviate this deformity and reduce ulcer risk. The established/traditional surgical approach is the triple hemisection along the length of the Achilles tendon. Although the percutaneous approach has been successful in achieving increases in ankle dorsiflexion >30°, the tendon rupture risk has led to some surgeons looking at alternative approaches. The gastrocnemius aponeurosis may be considered as an alternative because of the Achilles tendon's poor blood supply. ATL procedures are a balance between achieving adequate tendon lengthening and minimizing tendon rupture risk during or after surgery. After ATL surgery, the first 7 days should involve reduced loading and protected range of motion to avoid rupture, after which gradual reintroduction to loading should be encouraged to increase tendon strength. In summary, there is a moderate level of evidence to support surgical intervention for ankle joint equinus in patients with diabetes and forefoot ulceration that is non-responsive to other conservative treatments. Areas of caution for ATL procedures include the risk for overcorrection, tendon rupture and the tendon's poor blood supply. Further prospective randomized control trials are required to confirm the benefits of ATL procedures over conservative care and the most optimal anatomical sites for surgical intervention.

[Spontaneous Tendon Ruptures in the Rheumatoid Hand]. / Spontánní slachové ruptury v oblasti revmatické ruky.

A spontaneous tendon rupture is a direct consequence of rheumatoid inflammation and can appear without any noticeable impact, often during sleep. The patient then presents with inability to flex or extend metacarpophalageal or interphalangeal joints. Multiple ruptures resulting in impaired function of several fingers can also occur and markedly limit the hand's grip strength. A tear may arise from either mechanical injury to the tendon along its course over bone or connective tissues, or by biochemical action of lysosomal enzymes, released during the inflammation process, on the connective tissue of the tendon. Ischaemic damage to a part of the tendon due to constriction of vessels supplying the peritenonium is found in hypertrophic peri-tenosynovitis. Spontaneous ruptures can be prevented, in the first place, by early synovectomy and then by a number of prophylactic procedures on soft tissues and carpal bones, which can stop or at least slow down the development of severe axial deformities of the wrist and hand. Simple end-to-end suture of the stumps is usually not possible; tendon repair surgery using free grafts or, more often, intact tendon transfer is necessary. In the flexor part, transfer of the superficial flexor tendon to a stump of the deep flexor tendon is frequently performed; a free graft can also be used at a two-stage tendon reconstruction. The repair of flexor tendons is technically more demanding and the results are less satisfactory compared to repair surgery on the extensor tendon. Key words: rheumatoid arthritis, metacarpophalageal joint, interphalangeal joint, tendon rupture.

The clinical value of surgeons' efforts of preventing intraoperative tumor rupture in stage I clear cell carcinoma of the ovary: A Korean multicenter study.

OBJECTIVE: To demonstrate the survival impact of intraoperative tumor rupture in women with stage I clear cell carcinoma (CCC) of the ovary. METHODS: A total of 193 patients with stage I CCC of the ovary who had undergone a complete staging operation followed by ≥three cycles of adjuvant platinum-based chemotherapy, were retrospectively reviewed. Survival analysis was performed and compared between three stage groups: IA/IB, IC1, and IC2/IC3. RESULTS: There were 70, 51, and 72 women with ovarian CCC in stages IA/IB, IC1, and IC2/IC3, respectively. Intraoperative tumor rupture occurred in 69 (35.8%) patients. Gross endometriosis (p=0.020) and significant peritumoral adhesion (p<0.001) were associated with intraoperative tumor rupture. However, neither laparoscopic approach nor large tumor size >10cm were associated with intraoperative tumor rupture. Patients with stage IC2/IC3 compared to those with stage IC1, had poorer progression-free survival (PFS) (5-year PFS, 68.5% versus 91.7%; p=0.010) and overall survival (OS) (5-year OS, 81.1% versus 95.4%; p=0.027). However, there was no significant difference between patients with stages IA/IB and IC1 CCC in PFS (5-year PFS 88.8% versus 91.7%; p=0.291) and OS (5-year OS 94.6% versus 95.4%; p=0.444). Stage IC2/IC3 was the only independent poor prognostic factor for OS (hazard ratio, 3.50; 95% confidence interval, 1.31 to 9.36). CONCLUSION: Surgical spillage of tumor cells does not appear to have a negative impact on survival outcomes of women with stage I ovarian CCC who received ≥three cycles of adjuvant platinum-based chemotherapy.

Hemodynamic analysis and treatment of an enlarging extrahepatic portal aneurysm: report of a case.

Aneurysms in the portal venous system are relatively rare. We report the case of an extrahepatic portal venous aneurysm, detected incidentally by ultrasonography. The patient, a 75-year-old woman, was initially observed over 18 months, during which time, the aneurysm grew from 36 mm × 32 mm to 51 mm × 37 mm in size, without symptoms. Hemodynamic analysis employing computational flow dynamics technique showed obvious turbulence in the aneurysm, and the wall shear stress (WSS) against that part of the aneurysmal wall was greater than in other sites. To prevent complications such as spontaneous rupture and portal vein thrombosis, the aneurysm was resected, with reconstruction of the portal trunk. While careful follow-up is sufficient for most portal venous aneurysms, its enlargement could indicate possible spontaneous rupture. The increased WSS against part of the aneurysmal wall most likely accounts for the aneurysm enlargement in this case.

[A Case of Malignant Lymphoma of the Spleen Infiltrating the Diaphragm Treated with Splenectomy].

A 67-year-old man was treated for diabetes mellitus by his family doctor. A splenic tumor was suspected based on his pain in the left side of the abdomen. He was admitted to our hospital for close inspection and medical treatment. Abdominal CT and MRI scans showed a tumor, 10 cm in diameter, in the spleen. An opaque boundary with the diaphragm was also observed. On PET-CT, accumulations of FDG were observed in the left supraclavicular fossa and the left axilla. The serum levels of LDH and sIL-2R were elevated, and therefore a diagnosis of malignant lymphoma was suspected. Due to the risk of splenic rupture, a splenectomy was performed. After pathological examination, the patient was diagnosed with diffuse large B-cell malignant lymphoma. He is currently being treated with chemotherapy at another medical institute. Splenic rupture occurs in some cases of splenic malignant lymphoma, although the number of reported cases is low. In some of the cases, splenic rupture occurred during treatment of the malignant lymphoma. There is no specific way to measure the risk of splenic rupture; however, performing a prophylactic splenectomy is one option in cases where tumor cells have extended to the capsula lienis, similar to that in our patient.

Single center TAVR experience with a focus on the prevention and management of catastrophic complications.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an important treatment option for patients with severe symptomatic aortic stenosis (AS) who are inoperable or at high risk for complications with surgical aortic valve replacement. We report here our single-center data on consecutive patients undergoing transfemoral (TF) TAVR since the inception of our program, with a special focus on minimizing and managing complications. METHODS: The patient population consists of all consecutive patients who underwent an attempted TF-TAVR at our institution, beginning with the first proctored case in May 2006, through December 2012. Clinical, procedural, and echocardiographic data were collected by chart review and echo database query. All events are reported according to Valve Academic Research Consortium-2. RESULTS: During the study period, 255 patients with AS had attempted TF-TAVR. The procedure was successful in 244 (95.7%) patients. Serious complications including aortic annular rupture (n = 2), coronary occlusion (n = 2), iliac artery rupture (n = 1), and ventricular embolization (n = 1) were successfully managed. Death and stroke rate at 30 days was 0.4% and 1.6%, respectively. One-year follow-up was complete in 171 (76%) patients. One-year mortality was 17.5% with a 3.5% stroke rate. Descending aortic rupture, while advancing the valve, was the only fatal procedural event. There were 24.4% patients with ≥2+ aortic regurgitation. CONCLUSIONS: TAVR can be accomplished with excellent safety in a tertiary center with a well-developed infrastructure for the management of serious complications. The data presented here provide support for TAVR as an important treatment option, and results from randomized trials of patients with lower surgical risk are eagerly awaited.

Totally percutaneous versus standard femoral artery access for elective bifurcated abdominal endovascular aneurysm repair.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are a vascular condition with significant risk attached, particularly if they rupture. It is, therefore, critical to identify and repair these as an elective procedure before they rupture and require emergency surgery. Repair has traditionally been an open surgical technique that required a large incision across the abdomen. More recently endovascular aneurysm repairs (EVARs) have become a common alternative. In this procedure, the common femoral artery is exposed via a cut-down approach and a graft is introduced to the aneurysm in this way. This review examines a totally percutaneous approach to EVAR. This technique gives a minimally invasive approach to femoral artery access that may reduce groin wound complication rates and improve recovery time. The technique may, however, be less applicable in patients with, for example, groin scarring or arterial calcification. OBJECTIVES: This review aims to compare the clinical outcomes of percutaneous access with standard femoral artery access in elective bifurcated abdominal endovascular aneurysm repair (EVAR). SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched their Specialised Register (last searched July 2013), CENTRAL (2013, Issue 6) and clinical trials databases. Reference lists of retrieved articles were checked. SELECTION CRITERIA: Only randomised controlled trials were considered. The primary intervention was a totally percutaneous endovascular repair. All device types were considered. This was compared against standard femoral artery endovascular repair. Only studies investigating elective repairs were considered. Studies reporting emergency surgery for a ruptured abdominal aortic aneurysm (rAAA) and those reporting aorto-uni-iliac repairs were excluded. DATA COLLECTION AND ANALYSIS: All data were collected independently by two review authors. Owing to the small number of trials identified, no formal assessment of heterogeneity or sensitivity analysis was conducted. MAIN RESULTS: Only one trial met the inclusion criteria, involving a total of 30 participants, 15 undergoing the percutaneous technique and 15 treated by the standard femoral cut-down approach. There were no significant differences between the two groups at baseline.No mortality or failure of aneurysm exclusion was observed in either group. Three wound infections occurred in the standard femoral cut-down group, whereas none were observed in the percutaneous group. This was not statistically significant. Only one major complication was observed in the study, a conversion to the cut-down technique in the percutaneous access group. No long-term outcomes were reported. One episode of a bleeding complication was reported in the percutaneous group. Significant differences were detected in surgery time (percutaneous 86.7 ± 27 minutes versus conventional 107.8 ± 38.5 minutes; P < 0.05).The included study had a small sample size and failed to report adequately the method of randomisation, allocation concealment and the pre-selected outcomes. AUTHORS' CONCLUSIONS: Only one small study was identified, which did not provide adequate evidence to determine the efficacy and safety of the percutaneous approach compared with endovascular aneurysm repairs. This review has identified a clear need for further research into this potentially beneficial technique. One ongoing study was identified in the search, which may provide an improved evidence base in the future.

Comparative analysis of laparoscopy versus laparotomy in the management of ovarian cyst during pregnancy.

AIM: The aim of the present study was to evaluate the surgical and obstetric results of laparoscopy versus laparotomy in the management of ovarian cyst during pregnancy. MATERIAL AND METHODS: Sixty-nine eligible patients who met our criteria were randomly divided into the laparoscopy group (n = 33) and the laparotomy group (n = 36). The two groups were compared for their surgical and obstetric outcomes and the extent of pelvic adhesion discovered in later cesarean section (CS). RESULTS: The laparoscopy group had less blood loss (43 ± 15 vs 51 ± 13 mL, P = 0.02), shorter postoperative hospital stay (2.9 ± 0.5 vs 5.8 ± 0.6 days, P < 0.001), and lower postoperative pain score (2.7 ± 1.2 vs 5.9 ± 1.5, P < 0.001) compared with the laparotomy group. The operative time, neonates' Apgar scores and birthweights between the two groups showed no significant differences (P > 0.05). Sixteen patients in the laparoscopy group, and 15 patients in the laparotomy group underwent cesarean section. The filmy and dense type adhesion rate was significantly different between the laparoscopy group and the laparotomy group (6.25% vs 53.3%, and 0% vs 20%, respectively). CONCLUSIONS: The present results suggest that laparoscopy is a better choice than laparotomy for ovarian cyst during pregnancy, with less blood loss, less postoperative pain and less postoperative hospital stay. It offers a faster recovery, results in less pelvic adhesion and does not affect the fetus; however, studies encompassing larger numbers of cases are needed.

Targeted PET/CT imaging of vulnerable atherosclerotic plaques: microcalcification with sodium fluoride and inflammation with fluorodeoxyglucose.

A significant majority of atherosclerotic plaque ruptures occur in coronary arteries exhibiting none or only modest luminal narrowing on coronary angiography. Emerging data suggest the biological composition of an atherosclerotic plaque (vulnerability to rupture) rather than its degree of stenosis or size is the major determinants for acute clinical events. Thus, the pursuit for noninvasive molecular imaging probes that target plaque composition, such as inflammation and/or microcalcification is a creditable goal. 18 F-fluorodioxyglucose (18 F-FDG) is a metabolic probe that can be imaged using positron emission tomography (PET)/computer tomography (CT) technology to target plaque macrophage glucose utilization and inflammation. Vascular plaque 18 F-FDG uptake has been linked to cardiovascular events such as myocardial infarction and stroke. More recently, another molecular probe 18 F-sodium fluoride (18 F-NaF) was introduced for PET imaging, which targets active microcalcifications in atherosclerotic plaques. Little is known regarding the role of early microcalcification in the initiation and progression of plaque, partly because of lack of a noninvasive imaging modality targeting molecular calcification. 18 F-NaF PET/CT imaging could provide new insights into the complex interaction of plaque, and facilitate understanding the mechanism of plaque calcification. Moreover, when these 2 molecular probes, 18 F-FDG and 18 F-NaF, that target distinct biological processes in an atherosclerotic plaque are used in combination, they may further elucidate the link between local inflammation, microcalcification, progression to plaque rupture, and cardiovascular event.

Systematic review of haemorrhage and rupture of hepatocellular adenomas.

BACKGROUND: Although benign in itself, hepatocellular adenoma (HCA) can be complicated by hormone-induced growth, and subsequent haemorrhage and rupture. The exact risk of haemorrhage and rupture is not known. This systematic review of the literature was carried out with the aim of estimating the risk of haemorrhage and rupture in HCA. METHODS: A systematic literature search of the PubMed and Embase databases was performed for all articles relevant to haemorrhage and/or rupture of HCA, published between 1969 and March 2011. RESULTS: Twenty-eight articles met the selection criteria, containing a total of 1176 patients. Haemorrhage was reported with an overall frequency of 27·2 per cent among patients, and in 15·8 per cent of all HCA lesions. Rupture and intraperitoneal bleeding were reported in 17·5 per cent of patients. Bleeding was the first symptom in 68·5 per cent of patients with a bleeding HCA. Six of 13 articles reporting the size of HCA lesions in which bleeding occurred mentioned haemorrhage in HCAs smaller than 5 cm. CONCLUSION: Haemorrhage and rupture are common in patients with HCA.

Fibrin-thrombin coated sealant increases strength of esophagogastric anastomoses in a rat model.

BACKGROUND: Anastomotic leakage is a feared complication after esophagectomy. The purpose of this study was to investigate whether the use of a fibrin-thrombin coated collagen patch (TachoSil; Nycomed, Zurich, Switzerland), applied as a sealant, would strengthen the esophagogastric anastomosis and stimulate anastomotic healing in a rat model. METHODS: Hand sewn, end-to-side esophagogastric anastomoses were performed in 54 rats. Animals were randomized for an unsealed or sealed anastomosis. Rats were sacrificed on postoperative d 0, 3, 5, and 7. Primary parameter was bursting pressure. Secondary outcomes were complications, weight, and immunohistochemical staining for collagen formation and fibroblast activity. RESULTS: Bursting pressure at d 0 and 3 was significantly increased when a sealant was used (55.1 ± 4.6 mmHg versus 102.4 ± 7.3 mmHg, P < 0.010; and 19.7 ± 3.3 mmHg versus 34.6 ± 4.9 mmHg, P < 0.050 respectively). There was no difference in bursting pressure at d 5 and 7 between unsealed and sealed anastomoses (60.9 ± 18.2 mmHg versus 53.4 ± 6.6 mmHg, P = 0.690; and 118.8 ± 20.2 mmHg versus 97.2 ± 8.3 mmHg, P = 0.374 respectively). Application of sealant independently influenced bursting pressure (P < 0.010). Increased fibroblastic activity was noticed at d 7 in sealed anastomoses (P < 0.050). There were no differences in weight gain between groups. CONCLUSIONS: Additional sealing of the anastomosis increased anastomotic strength during early postoperative recovery when anastomotic strength is at its weakest. The findings indicate that sealing of the anastomosis has the potential to prevent leakage after esophagectomy in humans.

Ectopic pregnancy: History, incidence, epidemiology, and risk factors.

Ectopic pregnancy is directly related to tubal infection, and so prevention of chlamydia and gonorrhea must be the watchword to lower its risk and incidence. With accurate determination of very low human chorionic gonadotropin concentrations and sonography, >85% of women are diagnosed before tubal rupture, which has led to medical therapy and laparoscopic surgery with tubal preservation and the potential for future fertility. Today, early intervention saves lives and reduces morbidity, but ectopic pregnancy still accounts for 4% to 10% of pregnancy-related deaths and leads to a high incidence of ectopic site gestations in subsequent pregnancies.

hCG in ectopic pregnancy.

Ectopic pregnancies remain an important cause of morbidity and mortality in women of reproductive age. Management of these pregnancies has changed dramatically over the years. Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of 2 dissimilar subunits, alpha and beta, joined non-covalently. The free beta-subunit is the principal immuno-reactive agent in pregnancy serum samples. Improved diagnostic methods using hCG levels in combination with transvaginal ultrasound have lead to earlier detection rates, subsequent treatment and a reduction in mortality resulting from ectopic pregnancies. This chapter will describe current trends in ectopic pregnancy diagnosis based on hCG levels.

Management of hepatocellular adenoma during pregnancy.

BACKGROUND & AIMS: Hepatocellular adenoma in pregnant women requires special considerations because of the risk of hormone induced growth and rupture. To prevent these potential lethal complications, pregnancy is either often discouraged or the surgical resection of large adenomas is recommended. It may be questioned whether it is justified to deny a young woman a pregnancy, as the biological behaviour of hepatocellular adenoma may be less threatening than presumed. In this study we establish the management of hepatocellular adenoma during pregnancy based on our own experience and literature. METHODS: Twelve women with documented hepatocellular adenoma were closely monitored during a total of 17 pregnancies between 2000 and 2009. Their files were reviewed. RESULTS: In four cases, hepatocellular adenomas grew during pregnancy, requiring a Caesarean section in one patient (two pregnancies) at 36 and 34 weeks because of an assumed high risk of rupture. In one case radiofrequency ablation therapy was applied in the first trimester to treat a hormone sensitive hepatocellular adenoma, thereby excluding potential growth later in pregnancy. No intervention was performed in the other 14 cases and all pregnancies had an uneventful course with a successful maternal and fetal outcome. CONCLUSIONS: A "wait and see" management may be advocated in pregnant women presenting with a hepatocellular adenoma. In women with large tumours or in whom hepatocellular adenoma had complicated previous pregnancies, surgical resection may be recommended. In women with smaller adenomas it may no longer be necessary to discourage pregnancy.

Pleiotropic roles of S100A12 in coronary atherosclerotic plaque formation and rupture.

Macrophages, cytokines, and matrix metalloproteinases (MMP) play important roles in atherogenesis. The Ca(2+)-binding protein S100A12 regulates monocyte migration and may contribute to atherosclerosis by inducing proinflammatory cytokines in macrophages. We found significantly higher S100A12 levels in sera from patients with coronary artery disease than controls and levels correlated positively with C-reactive protein. S100A12 was released into the coronary circulation from ruptured plaque in acute coronary syndrome, and after mechanical disruption by percutaneous coronary intervention in stable coronary artery disease. In contrast to earlier studies, S100A12 did not stimulate proinflammatory cytokine production by human monocytes or macrophages. Similarly, no induction of MMP genes was found in macrophages stimulated with S100A12. Because S100A12 binds Zn(2+), we studied some functional aspects that could modulate atherogenesis. S100A12 formed a hexamer in the presence of Zn(2+); a novel Ab was generated that specifically recognized this complex. By chelating Zn(2+), S100A12 significantly inhibited MMP-2, MMP-9, and MMP-3, and the Zn(2+)-induced S100A12 complex colocalized with these in foam cells in human atheroma. S100A12 may represent a new marker of this disease and may protect advanced atherosclerotic lesions from rupture by inhibiting excessive MMP-2 and MMP-9 activities by sequestering Zn(2+).

Internal modulation of proteolysis in vascular extracellular matrix remodeling: role of ADAM metallopeptidase with thrombospondin type 1 motif 5 in the development of intracranial aneurysm rupture.

Intracranial aneurysms (IAs) are common cerebrovascular diseases that carry a high mortality rate, and the mechanisms that contribute to IA formation and rupture have not been elucidated. ADAMTS-5 (ADAM Metallopeptidase with Thrombospondin Type 1 Motif 5) is a secreted proteinase involved in matrix degradation and ECM (extracellular matrix) remodeling processes, and we hypothesized that the dysregulation of ADAMTS-5 could play a role in the pathophysiology of IA. Immunofluorescence revealed that the ADAMTS-5 levels were decreased in human and murine IA samples. The administration of recombinant protein ADAMTS-5 significantly reduced the incidence of aneurysm rupture in the experimental model of IA. IA artery tissue was collected and utilized for histology, immunostaining, and specific gene expression analysis. Additionally, the IA arteries in ADAMTS-5-administered mice showed reduced elastic fiber destruction, proteoglycan accumulation, macrophage infiltration, inflammatory response, and apoptosis. To further verify the role of ADAMTS-5 in cerebral vessels, a specific ADAMTS-5 inhibitor was used on another model animal, zebrafish, and intracranial hemorrhage was observed in zebrafish embryos. In conclusion, our findings indicate that ADAMTS-5 is downregulated in human IA, and compensatory ADAMTS-5 administration inhibits IA development and rupture with potentially important implications for treating this cerebrovascular disease.

[Prevention of rupture of atherosclerotic plaque by Candesartan in rabbit model].

OBJECTIVE: To evaluate Candesartan therapeutic effect against atherosclerotic plaque rupture and to explore the related mechanisms. METHODS: Thirty-four New Zealand White male rabbits were randomly divided into three groups: the control group, the model control group and the Candesartan intervention group. The control group rabbits were fed with a normal diet. Rabbits of the latter two groups were fed with a 1% high-cholesterol diet and received a balloon catheter injury respectively one week after the cholesterol feeding. Candesartan (0.5 mgⁱkg⁻¹â±d⁻¹) was given to the Candesartan group rabbits 2 days before the performance of the balloon catheter injury. By the end of 12(th) week of the experiment, Russell's viper venom was used for rabbits of both the model control and the Candesartan groups in order to induce rupture of the plaques developed and followed by sacrifice of all the rabbits of the 3 groups. The aortas were removed and fixed for histological evaluation. Immunohistochemistry of MMP-9, macrophage markers and collagen were performed. The protein expression of MMP-9 was determined using Western blot analysis. RESULTS: In the model control group, 7 of 9 rabbits with a total of 12 plaques developed rupture and thrombosis of the plaques after the induction. In contrast, only 2 of 10 rabbits with a total of 3 plaques demonstrated rupture and thrombosis in the Candesartan group (P < 0.05). The control group rabbits did not have plaque rupture and thrombosis. Compared with the model group, both the percentage area of MMP-9 and macrophages in the plaques were significantly decreased in the Candesartan group (12.35% ± 4.28% vs 32.58% ± 9.16%, P < 0.05; 13.87% ± 4.91% vs 23.8% ± 7.45%, P < 0.05). There was an increased percentage of collagen content in total plaques of the Candesartan group (30.27% ± 11.36% vs 4.18% ± 1.28%, P < 0.01). Compared with the model group, the protein expression of MMP-9 was significantly decreased in the Candesartan group (P < 0.01). CONCLUSION: Candesartan has a preventive value against atherosclerotic plaque rupture in hypercholesterolemic rabbits, likely through its reduction of MMP-9 expression, inhibition of macrophage accumulation and increase of collagen content within the plaques.