Maurizio Grosso

Hyperdynamic circulation in patients with cirrhosis: direct measurement of nitric oxide levels in hepatic and portal veins

BACKGROUND/AIMS Peripheral vasodilation represents the main vascular dysfunction associated with the hyperdynamic circulation of liver cirrhosis. This study was intended to measure directly regional and systemic levels of nitric oxide, a potent vasorelaxing mediator, in order to assess its role in the development of hemodynamic changes of cirrhosis. METHODS We compared nitric oxide levels in the splanchinic and systemic circulation of 25 patients with cirrhosis undergoing transjugular intrahepatic portosystemic stent shunt and in the hepatic vein and peripheral blood of 10 patients without cirrhosis submitted to venous catheterization. Nitric oxide levels were measured through electron paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes. RESULTS Significantly higher nitric oxide levels were calculated in patients with cirrhosis with respect to controls, both in the peripheral and hepatic veins. In patients with cirrhosis, nitric oxide levels in the portal vein (3.44 +/- 2.17, expressed in arbitrary units) were higher than in the systemic circulation (1.89 +/- 1.15), but lower than in the hepatic vein (4.75 +/- 2.53; p < 0.001 by variance analysis). CONCLUSIONS These data suggest that nitric oxide synthetic pathway activity as well as nitric oxide release are enhanced at the level of splanchnic vasculature and, more important, in the hepatic tissue, confirming evidence of the predominant role of nitric oxide in the pathogenesis of hemodynamic changes in patients with cirrhosis with portal hypertension.

Effect of Preoperative Radiological Treatment of Hepatocellular Carcinoma Before Liver Transplantation: A Retrospective Study

AbstractPurpose: To assess the results of radiological treatment of patients with hepatocellular carcinoma (HCC) performed before orthotopic liver transplantation (OLT). Methods: Sixty-two transplanted patients with a total of 89 HCC nodules were studied; 50 lesions in 38 patients had been treated prior to OLT with transcatheter arterial chemoembolization (TACE: n=29), percutaneous ethanol injection (PEI; n=10), or combined therapy (TACE+PEI; n=11). The induced necrosis was pathologically evaluated. The recurrence rate after OLT in the treated group of patients (n=38) was compared with that in the non-treated group (n=24). Results: After TACE, necrosis was complete in 7 of 29 lesions (24.1%), partial in 11 of 29 (37.9%), and absent in 11 of 29 (37.9%). After PEI, necrosis was complete in 8 of 10 lesions (80%), and partial in 2 of 10 (20%). Using combined therapy, necrosis was complete in 11 of 11 lesions (100%). Four of 24 untreated and 4 of 38 treated patients did not survive OLT from causes not related to the HCC; 3 of 20 non-treated patients (15%) and 4 of 34 treated patients (11.8%) had post-OLT recurrence (these last four patients had undergone only TACE and did not have tumor necrosis at pathological examination). Conclusion: TACE of HCC prior to OLT had no influence on the recurrence rate. PEI and combined therapy (TACE + PEI) may be recommended in patients awaiting OLT.

Treatment of a Hepatic Artery Aneurysm by Endovascular Exclusion Using the Multilayer Cardiatis Stent

The Cardiatis Multilayer stent (Cardiatis, Isnes, Belgium) is a cobalt self-expandable bare stent that has been available and approved for peripheral aneurysm management in European countries since May 2009. This stent consists of a three-dimensional braided tube made of two interconnected layers without any covering. The unique quality of this device is that it decreases flow velocity within the aneurysm vortex while improving laminar flow in the main artery and surrounding vital branches. This allows a pressure decrease within the aneurismal sac, stasis, and the formation of an organized thrombus. The Cardiatis Multilayer stent has been applied in experimental studies across aneurysms in many anatomic locations, including cerebral, aortic, and peripheral aneurysms. However, there are no publications in the literature describing multilayer implantation in the hepatic artery. The Cardiatis Multilayer stent is available in diameters ranging from 5 to 12 mm and lengths ranging from 30 to 120 mm. They use sheaths from 6F to 7F and require a 0.020-inch guidewire. Case Report

Combined evaluation of total and functional liver plasma flows and intrahepatic shunting

A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution ofd-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean ±sd) of the independent measurements of S and ICG hepatic clearance were 978±107 and 519±142 ml/min, respectively, while in cirrhotic patients they were 554±238 and 231±90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean±sd), calculated according to Ficks principle, were 1091±157 ml/min (S method) and 1033±153 ml/min (ICG method) in controls, and 1251±554 and 1284±677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation.

Palliative treatment of malignant refractory ascites by positioning of Denver peritoneovenous shunt.

Malignant ascites is relatively common in patients with certain types of end-stage cancer. Traditional treatments based on fluid and salt restriction and diuretic therapy often are not able to contain neoplastic ascites. These patients consequently undergo repeated abdominal paracentesis, with further plasma protein loss and risk of injury to abdominal viscera. The aim of this study was to evaluate our experience with Denver peritoneovenous shunt and the outcome of patients with malignant ascites and suggest some modifications to improve device patency. From February 1997 to December 1999, 44 Denver peritoneovenous shunts were placed in 42 patients, 17 women and 25 men, aged between 38 and 77 years (mean, 62.3), affected with malignant ascites due to advanced abdominal cancer. At the time of admission, 72% of patients had pain, 88% dysphagia, 66% nausea and/or vomiting, and 83% dyspnea. Eleven patients underwent local anesthesia with lidocaine and 33 general anesthesia with rapidly metabolized drugs. In 27 cases we used the peritoneal-internal jugular right vein surgical approach and in 3 cases the peritoneal-femoral vein surgical access, joining the saphena vein to the cross. In 10 cases, a radiological positioning of the Denver peritoneovenous shunt was effected by a trans-subclavian access. Relief of ascites symptoms was obtained in 87.5% of cases, with reduction of dyspnea, an increased appetite and improved ambulation. Denver peritoneovenous shunt is a good device to relieve malignant ascites, thereby reducing the risk of complications and the number of hospital admissions due to repeated paracentesis and consequently improving the quality of life. A careful patient selection, an accurate follow-up and some device modifications could improve the shunt performance, allowing a wider application of the Denver peritoneovenous shunt.

Percutaneous implantation of a catheter with subcutaneous reservoir for intraarterial regional chemotherapy: technique and preliminary results.

Purpose: We present the technique and the preliminary results of percutaneous implantation of intraarterial catheters connected to a subcutaneous infusion reservoir for prolonged regional chemotherapy of hepatic and extrahepatic tumors.Methods: Two hundred patients with primary or secondary hepatic neoplasms, pelvic, pancreatic, renal, lingual, and breast cancer underwent the procedure. The access was the left axillary artery (188 patients) and the femoral artery (12 patients). The catheter tip was placed in the hepatic (170 patients), hypogastric (18), splenic (4), internal thoracic (2), gastroduodenal (3), renal (2) or the external carotid artery (1). The catheter was connected to a subcutaneous reservoir and filled with heparin: chemotherapeutic infusion was subsequently started.Results: One hundred percent immediate technical success was obtained. Forty-three of 200 (21.5%) patients had a complication: 29 patients had a catheter dislodgment, nine had arterial thrombosis, three had a pseudoaneurysm of the left axillary artery and two had a port pocket hematoma. Most complications (37/43, 86%) were treated percutaneously without interruption of chemotherapy. In only six cases (3% of the total population) was chemotherapy discontinued due to the complication itself. The mean duration of catheter patency was 7.2 months.Conclusion: Percutaneous placement of an intraarterial catheter is feasible and causes less discomfort to the patient than the surgical approach. The technique has an acceptable complication rate (21.5%), similar to that for surgical implantation (17.8%), with the advantage that in most cases the complications can be resolved percutaneously. This technique represents an alternative to surgical implantation in the treatment of liver metastases from colorectal cancer and opens new therapeutic possibilities for the local prolonged treatment of other kinds of tumor, though its clinical efficacy must be assessed in selected trials.

Combined regional and systemic chemotherapy by a mini-invasive approach for the treatment of colorectal liver metastases.

&NA; From February 1996 to December 1998, 95 patients affected with colorectal liver metastases underwent the positioning of an intraarterial hepatic catheter by a transcutaneous subclavian access, under local anesthesia. All patients were evaluated for catheter implantation complications. Moreover, 61 patients of 95 treated at our center were retrospectively evaluated for results of chemotherapy performed with two different schedules of hepatic artery infusion (HAI) combined with systemic chemotherapy (SC). Eleven patients (group A) were treated with combined SC (5‐fluorouracil continuous infusion) and HAI (floxuridine). A subsequent 50 patients underwent HAI (floxuridine, 4 cycles) followed, if a response or stable disease were observed, by combined SC and HAI (group B). Three cases of aneurysm of subclavian artery occurred, which were treated by the positioning of a radiologic arterial stent and the reimplantation of the catheter by a femoral access. Thrombosis of the hepatic artery was registered in four cases. We observed 10.5% occurrence of dislocation of the catheter, which was always moved again in the hepatic artery. In group A, with 45% clinical objective response rate and 10% stable disease rate, median survival time and median time to extrahepatic progression were 9 and 6 months, respectively. In group B, we observed 44% clinical objective responses and 26% stable disease after HAI. Patients without disease progression and therefore submitted to sequential SC and HAI had a median survival time of 21 months and a median time to extrahepatic progression of 16 months. The development of the miniinvasive technique of implantation of an arterial port can avoid laparotomy for HAI. Percutaneous implantation of an arterial port has a low rate of technical complications. HAI followed by combined systemic and regional chemotherapy has good results in terms of survival and time to extrahepatic progression.

Fifteen years’ experience with transjugular intrahepatic portosystemic shunt (TIPS) using bare stents: retrospective review of clinical and technical aspects

PurposeThe authors present a retrospective analysis of a large series of patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement.Materials and methodsBetween March 1992 and December 2006, 658 patients were referred to our centre for TIPS placement. Indications for the procedure were digestive tract bleeding (52.8%), refractory ascites (35.3%), preservation of portal vein patency prior to liver transplantation (3.0%) and thrombosis of the suprahepatic veins (2.3%). Other indications (6.6%) included pleural ascites, portal thrombosis and hepatorenal and hepatopulmonary syndromes. All patients were evaluated with colour Doppler ultrasonography and in a few cases with computed tomography. The portal system was punctured under sonographic guidance. Wallstent, Palmaz and Nitinol thermosensitive stents were used. Embolisation of persistent varices was performed in 6.8% of cases.ResultsTechnical success was 98.9%. During a 1,500-day follow-up, the cumulative incidence of stent revision was 25.7% (Nitinol), 32.9% (Wallstent) and 1.8% (Palmaz). Mortality rates were 31.1%, 38.5% and 56.4%, respectively. The technical complications included six cases of heart failure, six of haematobilia, three of stent migration, two of intrahepatic haematoma and one of haemoperitoneum. Eight patients with severe portosystemic encephalopathy (PSE) were treated with a reduction stent.ConclusionsTIPS placement is safe and effective and may act as a bridge to liver transplantation. Ultrasonography plays a fundamental role in the preliminary assessment, in portal vein puncture and during the follow-up. Stent patency is satisfactory.RiassuntoObiettivoGli autori presentano un’analisi retrospettiva di un’ampia casistica di pazienti sottoposti a TIPS.Materiali e metodiSono giunti al nostro centro per la TIPS 658 pazienti tra il marzo 1992 e il dicembre 2006. Le indicazioni alla procedura erano: sanguinamento digestivo (52,8%), ascite refrattaria (35,3%), “tutela” della pervietà portale pre-trapianto epatico (3,0%), trombosi delle vene sovraepatiche (2,3%). Altre indicazioni (6,6%) erano ascite pleurica, trombosi portale, sindrome epato-renale ed epato-polmonare. I pazienti sono stati studiati con ecocolor doppler, raramente con tomografia computerizzata; la puntura portale è stata ecoguidata. Sono stati impiegati stent Palmaz, Wallstent e termoespandibili. Nel 6,8% dei casi sono state embolizzate varici persistenti.RisultatiIl successo tecnico è stato del 98,9%. Durante un follow-up di 1500 giorni, l’incidenza cumulativa di reintervento sugli stent è stata del 25,7% (Nitinol), 32,9% (Wallstent) e 1,8% (Palmaz); la mortalità è stata rispettivamente 31,1%, 38,5% e 56,4%. Le complicanze tecniche sono state: 6 insufficienze cardiache, 6 emobilie, 3 migrazioni di stent, 2 ematomi intraepatici ed 1 emoperitoneo. Otto pazienti con encefalopatia portosistemica (PSE) grave sono stati trattati con stent riduttore.ConclusioniLa TIPS è sicura ed efficace, può rappresentare un ponte all’OLT. L’ecografia ha un ruolo fondamentale nello studio preliminare, durante la puntura portale e nel follow-up. La pervietà degli stent è soddisfacente.

Radiofrequency Thermal Ablation of Small Tumors in Transplanted Kidneys: An Evolving Nephron-sparing Option

Small tumors in transplanted kidneys are rarely detected during follow-up. With surgical treatment, it is sometimes challenging to preserve the graft and its function. Image-guided ablation techniques have been recently reported as effective in treating these tumors. Herein three cases of radiofrequency (RF) thermal ablation in transplanted kidneys are reviewed and compared with cases in the literature. There were no major complications seen, the mean change in serum creatinine level was no greater than 0.1 mg/dL, and complete ablation was sustained on imaging studies at 3, 18, and 62 months follow-up. RF ablation can be considered a safe, function-preserving, and effective evolving therapeutic option for small tumors in transplanted kidneys.

Intra-arterial continuous infusion for treatment of pancreatic and biliary tract cancer

SummaryBackground. Systemic chemotherapy does not satisfactorily improve the poor prognosis of pancreas and biliary tract cancer unresectable or metastatic to the liver. Intra-arterial infusion of antineoplastic agents can give higher concentrations to the tumor and slighter concentrations to the whole body, with a potential of efficacy and lower toxicity, due to the hepatic clearance. Methods. Based on a safe and ambulatorial technique of transcutaneous arterial port implantation, this study was designed to evaluate feasibility and toxicity of 5-fluorouracil (5-FU) intra-arterial continuous infusion combined with systemic gemcitabine with dose escalation. Seventeen patients affected by pancreatic (14) or biliary tract (3) cancer received up to six cycles of treatment. Treatment consisted of intravenous gemcitabine on d 1 and 8 and intra-arterial 5-FU continuous infusion on d 1–14 every 21 d. Dose-escalation levels were 900 and 1000 mg/m2 for gemcitabine and 8, 10, 12, 15, and 17 mg/kg/d for 5-FU. Consecutive cohorts of three patients were planned at each dose level. Results. Gastrointestinal toxicity (vomiting and diarrhea [3rd–4th degree] and gastritis), constituted the dose-limiting toxicity, with a maximum-tolerated dose of 1000 mg/m2 for gemcitabine and 15 mg/kg/d for 5-FU. Hematological toxicity was present in a minority of patients. No patient had acute or later complications such as arterial thrombosis related to the implanted arterial port, sclerosis cholangitis, or chemical cholecistitis.Conclusion. 5-Fluorouracil intra-arterial continuous infusion, combined with systemic gemcitabine, seems to be a feasible and safe regimen that could give interesting results in pancreatic cancer.