An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells.

BACKGROUND: Ultrasound-responsive microbubbles offer a means of achieving minimally invasive, localised drug delivery in applications including regenerative medicine. To facilitate their use, however, it is important to determine any cytotoxic effects they or their constituents may have. The aim of this study was to test the hypothesis that phospholipid-shelled microbubbles are non-toxic to human bone-derived cells at biologically-relevant concentrations. METHODS: Microbubbles were fabricated using combinations of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC), polyoxyethylene(40) stearate (PEG40S) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene-glycol)-2000] (DSPE-PEG2000). Microbubble size and concentration were measured as a function of time and temperature by optical microscopy. Effects on MG63 osteosarcoma and human bone marrow stromal cells (BMSCs) were measured for up to 72 h by assay for viability, metabolic activity and proliferation. RESULTS: DBPC:DSPE-PEG2000 microbubbles were significantly more stable than DSPC:PEG40S microbubbles under all conditions tested. Serum-containing medium had no detrimental effect on microbubble stability, but storage at 37 °C compared to at 4 °C reduced stability for both preparations, with almost complete dissolution of microbubbles at times ≥24 h. DSPC:PEG40S microbubbles had greater inhibitory effects on cell metabolism and growth than DBPC:DSPE-PEG2000 microbubbles, with PEG40S found to be the principle inhibitory component. These effects were only evident at high microbubble concentrations (≥20% (v/v)) or with prolonged culture (≥24 h). Increasing cell-microbubble contact by inversion culture in a custom-built device had no inhibitory effect on metabolism. CONCLUSIONS: These data indicate that, over a broad range of concentrations and incubation times, DBPC:DSPE-PEG2000 and DSPC:PEG40S microbubbles have little effect on osteoblastic cell viability and growth, and that PEG40S is the principle inhibitory component in the formulations investigated.

Long-term results with the modified Sugiura procedure for the management of variceal bleeding: standing the test of time in the treatment of bleeding esophageal varices.

BACKGROUND: The surgical approaches to the treatment of bleeding esophageal varices in cirrhotic patients have been reduced since the clinical development of endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation. However, when acute sclerotherapy fails, and in cases where no further treatment is accessible, emergency surgery may be life saving. In the present study we retrospectively analyzed the results of the modified Sugiura procedure, performed as emergency and semi-elective treatment in the patient with bleeding esophageal varices. METHODS: Ninety patients with cirrhosis and portal hypertension were managed in our department for variceal esophageal bleeding between January 1985 and December 1992. The modified Sugiura procedure was performed in 46 patients on an emergency (25 patients) or semi-elective (21 patients) basis. Liver cirrhosis stage according to Child classification was A in 4 patients, B in 16 patients, and C in 26 patients. RESULTS: Acute bleeding was controlled in all patients. Postoperative mortality was 23.9% (11 of 46 patients). The mortality rate was 34.6% in Child class C patients (9 of 26 patients), and 12.5% in Child class B patients (2 of 16 patients). Twenty-four patients had long-term follow-up extending from 14 months to 22 years (mean 83.1 months). Ten of 24 patients (41.6%) did not develop rebleeding for 5-22 years (mean 10.3 years). Overall 5-year survival in these 24 patients was 62.5%. CONCLUSIONS: The modified Sugiura procedure remains an effective rescue therapy for patients with bleeding esophageal varices when alternative treatments fail or are not indicated. Moreover, it can be a life-saving procedure in patients with anatomy unsuitable for shunt surgery or for patients treated in nonspecialized centers where surgical expertise for a shunt operation is not available.

Renal angioplasty and stenting: is it still indicated after ASTRAL and STAR studies?

A renal artery stenosis (RAS) is common among patients with atherosclerosis, up to a third of patients undergoing cardiac catheterization. Fibromuscular dysplasia is the next cause of RAS, commonly found in young women. Atherosclerosis RAS generally progresses overtime and is often associated with loss of renal mass and worsening renal function (RF). Percutaneous renal artery stent placement is the preferred method of revascularization for hemodynamically significant RAS according to ACC and AHA guidelines. Several randomized trials have shown the superiority of endovascular procedures to medical therapy alone. However, two studies ASTRAL and STAR studies were recently published and did not find any difference between renal stenting and medical therapy. But these studies have a lot of limitations and flaws as we will discuss (poor indications, poor results, numerous complications, failures, poor technique, inexperienced operators, ecc.). Despite these questionable studies, renal stenting keeps indications in patients with: uncontrolled hypertension; ischemic nephropathy; cardiac disturbance syndrome (e.g. "flash" pulmonary edema, uncontrolled heart failure or uncontrolled angina pectoris); solitary kidney. To improve the clinical response rates, a better selection of the patients and lesions is mandatory with: good non-invasive or invasive imaging; physiologic lesion assessment using transluminal pressure gradients; measurements of biomarkers (e.g., BNP); fractional flow reserve study. A problem remains after renal angioplasty stenting, the deterioration of the RF in 20-30% of the patients. Atheroembolism seems to play an important role and is probably the main cause of this R.F deterioration. The use of protection devices alone or in combination with IIb IIa inhibitors has been proposed and seems promising as shown in different recent reports. Renal angioplasty and stenting is still indicated but we need: a better patient and lesion selection; improvements in techniques and maybe the use of protection devices to reduce the risk of RF deterioration after renal stenting.

Carotid angioplasty and stenting: how to avoid complications.

Carotid angioplasty and stenting (CAS) has been proposed as an alternative to surgery and is now more and more performed and well accepted, at least for high surgical risk patients. However complications and particularly embolic strokes, even with a meticulous technique, can occur at any step of the procedure. Silent embolism is detected after CAS and may be a problem that needs to be discussed. To avoid and reduce these complications associated with CAS we must have: good indications depending on good patients and lesions selection. New parameters have been proposed particularly for asymptomatic lesions, correct technique, embolic protection devices (EPD) are mandatory for any CAS. New techniques will be presented. The choice of the EPD depends on the clinical status of the patient, the lesion morphology and characteristics, the anatomy of the artery, good choice of the stent and correct implantation (all stents are not equivalent), pharmacological adjuncts, experienced operators, good team. With all these considerations CAS can now be performed with acceptable outcomes and in certain population the results are comparable or superior to surgery. The results of ongoing randomized trials are awaited.

Carotid angioplasty and stenting in octogenarians: is it safe?

PURPOSE: Elderly patients have a higher risk of complications in carotid endarterectomy. The aim of the study was to evaluate whether carotid artery stenting (CAS) performed in octogenarians also increases the procedure related risk. METHODS: 870 patients (male 626) mean age 70.9 +/- 9.3 years underwent 930 CAS for de novo lesions (n = 851) restenoses (n = 54) post radiation (n = 14) inflammatory arteritis (n = 9) post trauma aneurysms (n = 2). Indications for treatment: symptomatic carotid stenosis > or = 70% (n = 577) or asymptomatic stenosis > or = 80%. Patients were separated into two age groups: <80 years (749 patients, 806 CAS) and >80 years (121 patients, 124 CAS). 187 CAS performed without protection (N.P-) 6 patients >80 years, 743 with protection (NP+) (occlusion balloon: 334, filters: 404, reversal flow: 6) 118 patients >80 years. Data analysis included neurological complications, death and myocardial infarction (MI) rate at 30 days, anatomical particularities. Technical points will be described depending on the age of the patient. RESULTS: Technical success 804/806 in patients <80 years, 123/124 in patients >80 years (NS). 30 days outcomes: in the patient group <80 years we observed 9 TIA (1.1%) 3 without NP (1.7%) 6 with NP (0.9%), 5 minor strokes (0.6%) 2 without NP (1.1%) 3 with NP (0.5%), 3 major strokes: 2 without NP (1.1%) 1 with NP (0.2%), 5 deaths (0.6%) 2 without NP (1.1%) 3 with NP (0.5%). Death/stroke/MI: 14 (1.8%) 6 without NP (3.3%), 8 with NP (1.3%). In the group >80 years, we observed 2 TIA (1.7%) 1 without NP 1 with NP (0.92%) 1 minor stroke without NP (17%) no major stroke, no death. Death/stroke/MI 1 without NP (17%). CONCLUSION: CAS can be performed in elderly patients without higher risk than in younger patients. But good indications, a meticulous technique, protection devices are mandatory and some technical points must be pointed out to avoid neurological complications and failures.

Embolic protection for renal artery stenting.

UNLABELLED: A renal artery stenosis (RAS) is frequent and usually caused by atherosclerosis. Percutaneous renal artery angioplasty (PTRA) and stenting gives good immediate and long-term RESULTS: Concern has arisen in the postprocedural deterioration of the renal function (RF), which may occur in 20-40% of the patients therefore limiting the immediate benefits of the technique. Atheroembolism seems to play an important role in postprocedural deterioration. The authors postulated that the use of renal embolic protection devices could reduce the risk of renal embolism and avoid deterioration of the RF. One hundred forty-eight PTRA and stenting procedures were performed under protection in 121 hypertensive patients (M: 85), mean age: 64.5+/-11.8 years (22-87) with atherosclerotic renal artery stenosis. Eleven patients had solitary kidneys and 48 had renal insufficiency. Both occlusion balloons (N=46) and filters (N=95) were used. Of the 95 filters, the new FiberNet EP system (Lumen Biomedical) was included. This filter has the ability to capture particles as small as 30-40 microns without compromising flow. Generated debris was then removed and analysed, and blood pressure and serum creatinine levels were followed. Immediate technical success: was achieved in 100% os the cases. 112/141 lesions were stented directly. Visible debris with Percusurge (Medtronic) was aspirated and removed under aspiration from all patients and in 80% of the cases with filters. Debris was aspirated in 100% of the cases completed with the FiberNet). The mean particulate retrieved with the Percusurge system was 98.1+/-60.0 mu with a mean diameter ranging from 201+/-76 m (38-6 206). Mean occlusion time was 6.55+/-2.46 min and mean time in situ (filters) 4.2+/-1.1 min. Five times more particulate was removed with the FiberNet than with current available filters. One acute RF deterioration was observed. The mean follow-up was 29.6+/-14 months and the mean creatinine level remained constant during follow-up. At 6 months (101 patients) one deterioration of the RF in a patient with renal insufficiency at baseline was observed, 25 improvements in patients with renal insufficiency were noted, and 73 stabilizations. In conclusion 99% of the patients were stabilized or improved. After 2 years (84 patients) 95% of the patients remained stabilized (N=60) or showed improvements (N=20), and 4 patients had deterioration of RF (5%). The preliminary results suggest the feasibility and safety of distal protection during renal interventions to protect against atheroembolism and consequential deterioration of RF after the procedure. The beneficial effects of this technique should be evaluated further in randomized studies.

Recent advances in renal artery stenting.

Renal artery stenosis (RAS) is frequent and increasingly recognized thanks to technical improvements in duplex ultrasound, magnetic resonance angiography, computed tomography (CT) scanning, systematic renal angiography during cardiac catheterisation, coronary procedures and particularly in hypertensive or multivascular diseased patients. Renal artery angioplasty and stenting is the first treatment to be proposed for patients suffering from RAS. This procedure is largely performed with very good technical results, good anatomical results, a low complication rate and a good long-term patency. The technique has proven to be beneficial for preserving RF and stabilizing or improving BP in a large number of patients. Nevertheless, deterioration in RF after the procedure in 20-30% of cases may limit the immediate benefits of this technique. Atheroembolism seems to play an important role. Renal angioplasty with protection devices seems a promising technique that might become the standard of care in the future. Even so, some problems remain: the cost of the technique; the best protection device needs to be determined; protection devices specifically designed for the renal arteries are needed; indications have to be specified. Larger, randomised studies are awaited to confirm the usefulness of the technique.

Percutaneous transluminal angioplasty of the subclavian arteries.

AIM: The aim of this study was to review the feasibility, safety and long-term results of subclavian artery (SA) angioplasty. METHODS: Over 14 years, 237 patients (males: 135; mean age: 64+/-12 years) underwent percutaneous treatment for SA occlusive disease. Indications for treatment were upper limb ischemia (n=125), vertebrobasilar insufficiency (n=128), coronary steal (n=11) and anticipated coronary bypass surgery in asymptomatic patients (n=26). A total of 192 arteries were stenosed and 45 occluded. Mean percentage stenosis was 81.9+/-7.6% and mean lesion length was 23.8+/-8.8 mm. Percutaneous techniques included retrograde femoral (n=163), brachial artery (n=47) access or both (n=14) and in 4 cases the ''pull through technique''. An isolated balloon angioplasty was performed in 59 cases. We implanted 132 balloon expandable stents and 32 self-expandable stents. RESULTS: Technical success was obtained in 223 lesions (94%). Only 31 occlusions were recanalized (69%). Four periprocedural events occurred (1.2%), 1 major (fatal) stroke, 1 transient ischemic attack and 2 arterial thromboses. At follow-up (mean follow-up: 65.8+/-33.5 months), we had 27 restenoses (12%). Thirteen occurred following angioplasty alone (18.8%) and 14 following angioplasty and stent implantation (8.4%). Primary (PI) and secondary (PII) patencies on an intention to treat basis at 10-year follow-up were 78.1% and 84.5%, respectively. In patients without initial stent placement, the rates were 67.5% and 75.5%, while in those with stents the rates rose to 89.7% and 96.9% (P<0.01). PI for all recanalized lesions were 84.6%, 79.1% without stent, 89.7% with stent (P<0.04) and PII 91.6%, 88.5%, 96.9%, respectively (P<0.02). CONCLUSION: Percutaneous transluminal angioplasty is currently the treatment of choice for SA lesions. It is a safe and effective procedure associated with low risks and good long-term results. Stents seem to limit the restenosis rate and improve long-term results.

Carotid angioplasty and stenting under protection. State of the art.

A carotid stenosis is responsible for about 30% of strokes occurring. Carotid endarterectomy (CEA) is considered to be the gold standard treatment of a carotid stenosis. Carotid angioplasty and stenting (CAS) is emerging as a new alternative treatment for a carotid artery stenosis, but the risk of neurological complications and brain embolism remain the major drawback to this procedure. So as to reduce the risk, we need: good indications, good patient and lesion selection; correct techniques; brain protection devices (cerebral protection devices should be routinely used and are mandatory for any procedure. Three types of protection devices are available: filters are the most commonly used. Nevertheless, all protection devices have limitations and cannot prevent from embolic events. However neurological complications can be reduced by 60%. New protection devices will be discussed); good choice of the stent and correct implantation (all stents are not equivalent and have different geometrical effects); pharmacological adjuncts; good team. Indications are well accepted for high-risk patients and recent studies have shown that CAS has superior short-term outcomes than CEA in this group of patients. Indications for low-risk and asymptomatic patients are controversial. New selection criteria have to be discussed. But there are enough reported data to conclude that CAS is also not inferior to CEA in low-risk and asymptomatic patients. In our series of 844 procedures, without protection (n = 187) 30-day death and stroke rate was 3.7% and with protection (n = 657) 1% (1.3% for symptomatic patients, 0.9% for asymptomatic patients, 1.4% in high-risk patients, 0.4% in low-risk patients). CAS under protection is the standard of care and is maybe becoming the gold standard treatment of a carotid stenosis at least in some subgroups of patients.

Carotid angioplasty and stenting under protection. Techniques, results and limitations.

A carotid stenosis is responsible for about 30% of strokes occurring. Carotid endarterectomy (CEA) is considered to be the gold standard treatment of a carotid stenosis. Carotid angioplasty and stenting (CAS) is emerging as a new alternative treatment for a carotid artery stenosis, but the risk of neurological complications and brain embolism remains the major drawback to this procedure. Therefore, in order to reduce the risks, we need: 1) good indications, good patient and lesion selection; 2) correct techniques; 3) brain protection devices (cerebral protection devices should be routinely used and are mandatory for any procedure); 4) 3 types of protection devices are available, but filters are the most commonly used (all protection devices have limitations and cannot prevent from all embolic events; however, neurological complications can be reduced by 60%); 5) a good choice of the stent and correct implantation (all stents are not equivalent and have different geometrical effects); 6) pharmacological adjuncts; 7) a good team. Recent studies have shown that CAS has superior short-term outcomes than CEA in high surgical risk patients, but there are enough reported data to conclude that CAS is also not inferior to CEA in low-risk patients. CAS under protection is the standard of care and is maybe becoming the gold standard treatment of a carotid stenosis at least in some subgroups of patients.

Angioplasty and stenting of extracranial vertebral artery stenosis.

Percutaneous angioplasty and stent placement seem a useful technique for the treatment of vertebro-basilar insufficiency and the first treatment to be proposed. This technique appears safe and effective for alleviating symptoms and improving blood flow to the cerebral circulation, with a low complications rate and good long-term results. However, this procedure needs experienced interventionists to choose the stent and have appropriate placement of the stent in the ostium of the vertebral artery (VA). The tortuosity of the VA may be technically challenging. The new coronary stents seem to be well suited to treat atherosclerotic lesions of the origin and of the proximal VA. A large variability of restenosis risk has been reported. Drug eluting stents may be the solution. Prospective randomized studies are needed to demonstrate the clinical effectiveness of VA stenting in stroke prevention, its durability, and to define more clearly its indications.

Are metal stents effective for palliation of malignant dysphagia and fistulas?

BACKGROUND: One of the available treatments for unresectable oesophagogastric malignancies is the insertion of metal stents. AIMS: We evaluated prospectively 147 patients suffering from malignant dysphagia and/or fistula, after inserting a self-expandable metal stent. PATIENTS AND METHODS: The study included 147 patients (87 males, mean age 73 years). Dysphagia before and after stent placement was scored. Patients were divided in two groups according to dysphagia grade: group A (grade 0, 1) and group B (grades 2, 3, 4). Three types of stents were used: the Ultraflex stent (covered and uncovered) and the Flamingo one (covered). The total number of self-expandable metal stents placed was 183. A total of 92 of them were inserted following the combined endoscopic and fluoroscopic approach (42 by injecting lipiodol), while 91 were placed under endoscopic control only. Early and late complications were evaluated. RESULTS: Mean dysphagia score in group A, 1 day and 1 month after the procedure, was slightly reduced from 0.8 to 0.5/0.6 (p=NS), respectively. However, there was a statistically significant improvement (p<0.001) of mean dysphagia score in group B, from 2.4 initially to 1.1/1.4. Early complications occurred in 37 cases, late ones in 51. According to severity, minor complications occurred in 24 patients, major in 42, while life-threatening ones in 22. Survival ranged from 1 to 611 days and 1-week mortality was 9%. Stent-related death occurred in six patients. CONCLUSIONS: All kinds of endoscopic methods used for stenting in the present study were easy to perform even on an out-patient basis. Insertion of self-expandable metal stents is effective in patients with dysphagia scores > or = 2. It might not clinically improve patients with dysphagia score <2, so selection of patients for stenting is essential to avoid unnecessary procedures. Moreover, their high cost, high complication rates and low overall survival may improve following better selection criteria.

Treatment of postoperative bronchobiliary fistula by nasobiliary drainage.

Bronchobiliary fistula (BBF) is a rare condition. It may present as a complication of echinococcal or amebic liver disease. Management of such a fistula can be very difficult and is often associated with a high rate of morbidity and mortality. We report the case of a 70-year-old woman who presented with a BBF after a one-stage operation for hydatid cysts of the liver and lung that were approached via thoracotomy and transdiaphragmatic incision. The cause of the BBF was an inflammatory collection in the residual liver cavity due to inadequate drainage. This collection eroded the sutured diaphragm, and because of the existing adhesions, it perforated directly into the bronchial system at the area of the previous cystectomy. Initially, endoscopic sphincterotomy was performed to achieve biliary decompression by equalizing intrabiliary and duodenal pressure, but no significant improvement was seen. Subsequently, nasobiliary drainage was instituted by means of an endoscopically inserted, nasobiliary catheter, which further reduced biliary pressure and facilitated biliary flow to the duodenum, as opposed to the fistulous tract. The fistula was successfully closed in a short time. This conservative method reduces the risks of reoperation. Therefore, it should be considered the treatment of choice in the management of bronchobiliary fistula.

Percutaneous balloon pericardiotomy for management of cardiac tamponade in a patient with lung cancer and large pericardial effusion.

We describe the case of a 32-year-old man with lung cancer involving the pericardium on which we performed pericardiotomy, using a balloon dilating catheter, to create a non-surgical pericardial window. For the percutaneous creation of pericardial window we advanced into the pericardium by subxiphoid approach a 0.035 inch guide wire through a 7f. pig-tail catheter. Subsequently a 22 mm diameter, 4 cm long balloon dilating catheter was advanced to the parietal pericardium and inflated for about 60 seconds until a tear in the pericardium was formed. We believe that percutaneous balloon pericardiotomy is helpful in the management of large pericardial effusions particularly in patients with malignancies and poor condition.

Evaluation during early puerperium of the low transverse incision after cesarean section through vaginal ultrasonography.

OBJECTIVE: This study was designed in order to determine the criteria of the natural healing of the low transverse cesarean incision through vaginal ultrasonography. METHODS: The uterine wound was examined with a vaginal scanner (5.5-7 MHz) in 75 asymptomatic patients with a normal postoperative course three days after the cesarean section. We compared our findings with those obtained in 21 patients with a complicated post-cesarean course. RESULTS: The uterine incision was identified as an oval, centrally located region between the bladder and the uterus. In 18 of the 75 cases, a hypoechoic area with indistinct limits, almost rounded and with a diameter of smaller than 1.5 cm in all cases was determined in the incision site. Possibly all these cases represented small hematomas or serous collections, with no clinical importance. Four of the 21 symptomatic patients had bladder flap or uterine incision hematomas. These were large (> 2 cm in all cases) hypoechoic areas inside or around the transverse incision site. CONCLUSION: The low transverse cesarean incision in the uterus can be visualized sonographically with a vaginal scanner and normal postoperative changes can be recognized.

[Idiopathic anal incontinence. Surgical treatment]. / Incontinence anale idiopathique. Cure chirurgicale.

Three patients operated upon for idiopathic anal incontinence are reported. This idiopathic incontinence is due to degeneration of the nerves supplying the pelvic floor muscles and results in partial or total disappearance of the double right angle which normally exists between the anal canal and the rectum. This anorectal angulation is essential in the maintenance of anal continence. The aim of the operation is the reconstruction of a normal anatomy with the restoration of this anorectal angulation. The suture of the levators ani and particularly of the puborectalis muscle proposed by Parks is the operation of choice. The results of the operation 1-3 years later are excellent in two cases and satisfactory in one case.