Vessel embolization can be a valuable adjunct procedure in transjugular intrahepatic portosystemic shunt (TIPS). During the creation of a TIPS, embolization of portal vein collaterals supplying esophageal varices may lower the risk of secondary rebleeding. And after creation of a TIPS, closure of the TIPS itself may be indicated if the resulting hepatic encephalopathy severely impairs mental functioning. The Amplatzer Vascular Plug (AVP; AGA Medical, Golden Valley, MN) is well suited for embolization of large-diameter vessels and has been employed in a variety of vascular lesions including congenital arteriovenous shunts. Here we describe the use of the AVP in the context of TIPS to embolize portal vein collaterals (n = 8) or to occlude the TIPS (n = 2).
Interventional radiology; Embolization; Amplatzer Vascular Plug; Varices; Transjugular intrahepatic portosystemic shunt
Hepatic encephalopathy (HE) is a cognitive disturbance characterized by neuropsychiatric alterations. It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts. The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration. Therefore, the embolization of these shunts has been performed to control HE manifestations, but the presence of portal vein thrombosis is considered a contraindication. In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt. Case report: a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma, even without precipitant factors. She had a wide portosystemic shunt and also portal vein thrombosis. The abdominal angiography confirmed the splenorenal shunt and showed other shunts. The larger shunt was embolized through placement of microcoils, and the patient had no recurrence of overt HE. There was a little increase of esophageal and gastric varices, but no endoscopic treatment was needed. Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients, portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization. However, in particular cases with many shunts and severe HE, we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery. In conclusion, we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis. As the patient had other shunts, she was successfully treated by embolization of the larger shunt.
Recurrent hepatic encephalopathy; Liver cirrhosis; Port systemic shunt; Shunt embolization; Portal vein thrombosis
Hepatic encephalopathy most commonly occurs in patients with cirrhosis and end-stage liver disease, however, the disorder can also occur in the presence of intra or extrahepatic shunts when the intrahepatic circulation is effectively bypassed. The majority of extrahepatic shunts described to date develop between a mesenteric vein and inferior vena cava. Herein we report a novel case of a superior mesenteric vein to left internal iliac vein shunt that led to hepatic encephalopathy in a 57 year old woman with no apparent underlying liver disorder. The patient presented with confusion, disorientation and hyperammonemia. Work-up for parenchymal liver disease was negative and liver biopsy findings did not show significant liver disease. Magnetic resonance imaging revealed a serpiginous 1 cm wide shunt that diverted superior mesenteric vein blood from the portal confluence to the left internal iliac vein. Surgical closure of the shunt led to marked improvement of the patient with resolution of hepatic encephalopathy. This report is the first description of a portosystemic shunt, likely congenital, linking these two vessels resulting in clinically significant hepatic encephalopathy. The findings emphasize that abdominal and pelvic imaging should be considered in patients with signs of hepatic encephalopathy that have none to minimal hepatic disease.
Hepatic Encephalopathy; Portosystemic shunt; Non-cirrhotic liver
Budd-Chiari syndrome is a spectrum of manifestations which develops as a result of hepatic venous outflow obstruction. Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive vascular and interventional radiological procedure indicated in the management of refractory ascites in such patients. Conventional TIPS requires the presence of a patent hepatic vein and reasonable accessibility to the portal vein, and in patients with totally occluded hepatic veins, this procedure is technically challenging. Direct intrahepatic portosystemic shunt (DIPS) or so called “percutaneous TIPS” involves ultrasound-guided percutaneous simultaneous puncture of the portal vein and inferior vena cava followed by introduction of a guidewire through the portal vein into the inferior vena cava, as a deviation from conventional TIPS. Described here is our experience with DIPS. Three patients with BCS who had refractory ascites but were unsuitable for conventional TIPS due to occlusion of the hepatic veins were chosen to undergo the DIPS procedure. Our technical success was 100%. The shunts placed in two patients remain patent to date, while the shunt in a third patient with underlying antiphospholipid syndrome was occluded a month after the procedure. The percutaneous TIPS procedure seems to be technically feasible and effective in the management of refractory ascites as a result of BCS, particularly in the setting of occluded hepatic veins.
Budd-Chiari syndrome; portal hypertension; transjugular intrahepatic portosystemic shunt; direct intrahepatic portosystemic shunt
Spontaneous splenorenal shunts in the absence of cirrhosis have rarely been reported as a cause hyperammonemia with encephalopathy. Several closure techniques of such lesions have been described. Here we report a case of a patient with no history of liver disease who developed significant confusion. After an extensive workup, he was found to have hyperammonemia and encephalopathy due to formation of a spontaneous splenorenal shunt. There was no evidence of cirrhosis on biopsy or imaging and no portal hypertension when directly measured. The shunt was 18 mm and too large for embolization so the segment of the splenic vein between the portal vein and the shunt was occluded using an Amplatzer plug. Thus, the superior mesenteric flow was directed entirely to the liver. After interventional radiology closure of the shunt using this technique there was complete resolution of symptoms. The case represents the first report of a successful closure of splenorenal shunt via percutaneous embolization of the splenic vein with an amplatzer plug using a common femoral vein approach.
Splenorenal shunt; Gastric bypass; Hyperammonemia; Encephalopathy
We present a case with hepatic myelopathy (HM) due to a surgical splenorenal shunt that was successfully treated by endovascular interventional techniques. A 39-year-old man presented with progressive spastic paraparesis of his lower limbs 14 mo after a splenorenal shunt. A portal venogram identified a widened patent splenorenal shunt. We used an occlusion balloon catheter initially to occlude the shunt. Further monitoring of the patient revealed a decrease in his serum ammonia level and an improvement in leg strength. We then used an Amplatzer vascular plug (AVP) to enable closure of the shunt. During the follow up period of 7 mo, the patient experienced significant clinical improvement and normalization of blood ammonia, without any complications. Occlusion of a surgically created splenorenal shunt with AVP represents an alternative therapy to surgery or coil embolization that can help to relieve shunt-induced HM symptoms.
Hepatic myelopathy; Shunts; Portosystemic; Hepatic encephalopathy; Embolization; Endovascular balloon occlusion; Interventional procedures; Amplatzer vascular plug
Purpose. Interventional treatment strategies for patients with encephalopathy due to splenorenal shunt remain controversial. Portosplenic blood flow separation by occluding the splenic vein could avoid the complication of severe portal hypertension, but it would require repeated reintervention due to recurrence of symptoms. This paper describes occlusion of the splenic vein using coil anchors and prophylactic embolization of a collateral hepatofugal vessel with no recurrence of hyperammonemia. Materials and Methods. A 51-year-old woman with severe cirrhosis had hepatic encephalopathy due to a large splenorenal shunt. The serum ammonia level was 132 μg/dL. Via a transileocolic approach, the splenic vein was completely embolized with 0.035-inch metallic coils using coil anchors while preserving the splenorenal shunt. In addition, one of the collateral vessels of the portal vein, the retrogastric vein, was also embolized prophylactically. Results. After this procedure, the serum ammonia level decreased immediately to 24 μg/dL. The portal venous pressure increased by only 1.5 mmHg. Hepatic encephalopathy had not been observed for 25 months after the procedure, and neither retention of ascites nor worsening of esophageal varices and liver function was observed. Conclusion. This procedure appears to be safe and effective for hepatic encephalopathy caused by a splenorenal shunt.
We report a 65-year-old man with hepatic encephalopathy due to an intrahepatic portosystemic venous shunt that was successfully occluded by balloon occluded retrograde transvenous embolization with Guglielmi and interlocking detachable coils as performed percutaneously.
Hepatic veins; interventional procedures; portal vein; therapeutic blockade; shunts; portosystemic
To describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage.
From October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up.
A 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days.
CARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding.
A congenital intrahepatic portosystemic shunt is a rare anomaly; but, the number of diagnosed cases has increased with advanced imaging tools. Symptomatic portosystemic shunts, especially those that include hyperammonemia, should be treated; and various endovascular treatment methods other than surgery have been reported. Hepatic masses with either an intra- or extrahepatic shunt also have been reported, and the mass is another reason for treatment. Authors report a case of a congenital intrahepatic portosystemic shunt with a hepatic mass that was successfully treated using a percutaneous endovascular approach with vascular plugs. By the time the first short-term follow-up was conducted, the hepatic mass had disappeared.
Portosystemic shunt, surgical; Liver neoplasm; Radiology, interventional
We report a case of stage IV breast cancer terminating in an unusual picture of radiologically occult micronodular pseudo-cirrhosis. Contrast-enhanced computed tomography showed no evidence of metastatic breast cancer within the liver. Unlike the few previously reported cases of intrasinusoidal spread of breast cancer, our patient was palliated with a transjugular intrahepatic portosystemic shunt along with salvage chemohormonal therapy. In addition, our patient demonstrated proof of the principle of the dependence of capecitabine (Xeloda) efficacy on dose scheduling as predicted by laboratory studies based on Gompertzian tumor growth and the Norton-Simon hypothesis.
We report the case of a 52-year-old Caucasian woman who developed radiological signs of portal hypertension without radiological evidence of hepatic metastasis five years after being diagnosed with metastatic breast cancer. She was receiving chemotherapy for stage IV breast cancer initially thought to be metastatic only to the bones. During salvage therapy with high-dose estradiol (Estradiol valerate), vinorelbine (Navelbine) and bevacizumab (Avastin), she suddenly developed signs of portal hypertension confirmed on computed tomography and by portal and systemic venous pressure measurements. Drug toxicity due to bevacizumab (Avastin) was initially and incorrectly entertained as a cause. The patient underwent palliative transjugular intrahepatic portosystemic shunt and transhepatic venous liver biopsy, which revealed the presence of rapidly progressive and uncontrolled metastatic breast cancer. The new discovery of radiologically occult intrasinusodal hepatic metastases with secondary micronodular cirrhosis was found to be the cause of her sudden onset portal hypertension. The patient's resistance to capecitabine (Xeloda) was reversed by changing the schedule of medication to biweekly 7/7 (7 days ingesting drug alternating with 7 days off drug) from the 14/7 (14 days ingesting drug alternating with a 7 day rest period) day schedule approved by the US Food and Drug Administration.
This case report demonstrates an unusual presentation of radiographically occult hepatic metastasis from breast cancer palliated with transjugular intrahepatic portosystemic shunt. All patients with advanced breast cancer developing unexpected portal hypertension should be considered candidates for liver biopsy despite normal computed tomography of the liver imaging results. This is the first report of a reversal of clinical resistance to capecitabine (Xeloda) by changing from the schedule of 14/7 day to a biweekly 7/7 day schedule. This suggests that a biweekly schedule may be best for some patients.
Endoscopic experience in the management of duodenal varices (DVs) is limited and challenging given the anatomic constraints and limited experience. The endovascular management of DVs is not yet established and the controversy of whether to manage them by decompression with a transjugular intrahepatic portosystemic shunt (TIPS) or by transvenous obliteration is unresolved. In the literature, the 6–12 month rebleeding rate of DVs after TIPS is 21-37% and after transvenous obliteration is 13%. The purpose of the study is to evaluate the clinical outcome of combined TIPS decompression and transvenous obliteration/sclerosis.
Materials and Methods:
This is a retrospective study (case series) of two institutions, evaluating patients who underwent TIPS and/or transvenous obliteration/sclerosis for bleeding DVs (from January 2009 to June 2013). TIPS was performed according to a standard procedure using covered stents. Transvenous obliteration (variceal sclerosis) from the systemic and/or portal venous circulation was performed utilizing 3% sodium tetradecyl sulfate foam. Transvenous obliteration was commonly augmented with coils and/or vascular plugs. Technical (technical success of establishing TIPS and completely obliterating the DVs) and clinical outcomes (rebleeding rate and survival) were evaluated.
Five patients with liver cirrhosis presenting with bleeding DVs were included in the study with all eventually (and coincidentally) receiving TIPS and transvenous obliteration. Two of the five patients underwent concomitant TIPS and transvenous obliteration in the same procedural setting. However, three patients underwent transvenous obliteration due to bleeding despite a patent TIPS that had been previously placed. The average time from TIPS placement to transvenous obliteration was 125 days (range: 3-324 days). After having both procedures, there was no rebleeding in the patients during a mean follow-up period of 22 months (6–50 months). Coils and/or metallic vascular plugs were used to augment the sclerosant obliteration in four of five patients.
The combination of TIPS decompression and foam sclerosant transvenous obliteration appears to be effective in preventing rebleeding in this limited case series and compares favorably with the existing evidence for either approach [TIPS or balloon-occluded retrograde transvenous obliteration (BRTO)] alone.
Balloon-occluded retrograde transvenous obliteration; bleeding; duodenal varices; vascular plugs
AIM: To review percutaneous transhepatic portal venoplasty and stenting (PTPVS) for portal vein anastomotic stenosis (PVAS) after liver transplantation (LT).
METHODS: From April 2004 to June 2008, 16 of 18 consecutive patients (11 male and 5 female; aged 17-66 years, mean age 40.4 years) underwent PTPVS for PVAS. PVAS occurred 2-10 mo after LT (mean 5.0 mo). Three asymptomatic patients were detected on routine screening color Doppler ultrasonography (CDUS). Fifteen patients who also had typical clinical signs of portal hypertension (PHT) were identified by contrast-enhanced computerized tomography (CT) or magnetic resonance imaging. All procedures were performed under local anesthesia. If there was a PVAS < 75%, the portal pressure was measured. Portal venoplasty was performed with an undersized balloon and slowly inflated. All stents were deployed immediately following the predilation. Follow-ups, including clinical course, stenosis recurrence and stent patency which were evaluated by CDUS and CT, were performed.
RESULTS: Technical success was achieved in all patients. No procedure-related complications occurred. Liver function was normalized gradually and the symptoms of PHT also improved following PTPVS. In 2 of 3 asymptomatic patients, portal venoplasty and stenting were not performed because of pressure gradients < 5 mmHg. They were observed with periodic CDUS or CT. PTPVS was performed in 16 patients. In 2 patients, the mean pressure gradients decreased from 15.5 mmHg to 3.0 mmHg. In the remaining 14 patients, a pressure gradient was not obtained because of > 75% stenosis and typical clinical signs of PHT. In a 51-year-old woman, who suffered from massive ascites and severe bilateral lower limb edema after secondary LT, PVAS complicated hepatic vein stenosis and inferior vena cava (IVC) stenosis. Before PTPVS, a self-expandable and a balloon-expandable metallic stent were deployed in the IVC and right hepatic vein respectively. The ascites and edema resolved gradually after treatment. The portosystemic collateral vessels resulting from PHT were visualized in 14 patients. Gastroesophageal varices became invisible on poststenting portography in 9 patients. In a 28-year-old man with hepatic encephalopathy, a pre-existing meso-caval shunt was detected due to visualization of IVC on portography. After stenting, contrast agents flowed mainly into IVC via the shunt and little flowed into the portal vein. A covered stent was deployed into the superior mesenteric vein to occlude the shunt. Portal hepatopetal flow was restored and the IVC became invisible. The patient recovered from hepatic encephalopathy. A balloon-expandable Palmaz stent was deployed into hepatic artery for anastomotic stenosis before PTPVS. Percutaneous transhepatic internal-external biliary drainage was performed in 2 patients with obstructive jaundice. Portal venous patency was maintained for 3.3-56.6 mo (mean 33.0 mo) and all patients remained asymptomatic.
CONCLUSION: With technical refinements, early detection and prompt treatment of complications, and advances in immunotherapy, excellent results can be achieved in LT.
Portal vein; Anastomotic stenosis; Venoplasty; Stent; Liver transplantation
From being a mere (though important) diagnostic tool, radiology has evolved to become an integral part of therapy in portal hypertension today. Various procedures are currently available, the choice depending on the etiology and location of disease, the pathoanatomy, and the symptomatology. The main aim of any procedure is to reduce the portal pressure by either direct or indirect methods. This can be achieved with transjugular intrahepatic portosystemic shunt (TIPS), recanalization of the hepatic vein outflow, recanalization of the portal vein and its tributaries, recanalization of dysfunctional portosystemic shunts, partial splenic embolization, and embolization of arterioportal shunts. When any of these procedures cannot be performed due to anatomical or physiological reasons, the symptoms can often be controlled effectively with embolization of varices or balloon-occluded retrograde transvenous obliteration of varices (BRTO). This article briefly describes the procedures, their results, and their current status in the treatment of portal hypertension.
Interventional radiology; portal hypertension
Aneurysmal rupture of the intra-cavernous carotid artery may cause idiopathic carotid-cavernous fistula (CCF), and the treatment choice for occluding shunting fistula in this type of CCF is an endovascular approach using detachable balloons. However, little has been reported on treating such lesions with the intra-aneurysmal embolization using Guglielmi detachable coils (GDCs). To our knowledge, ours is the first reported case of successful treatment by selective intra-fistula and intra-aneurysmal embolization with GDCs. A 74-year-old woman exhibited proptosis and chemosis of her left eye over a period of one month. Symptoms of double vision in conversion and pulsatile murmur in her left eye were also noted. Angiography revealed an intra-cavernous aneurysm of the left internal carotid artery (ICA) with a shunting fistula, which drained into the dilated cavernous sinus, superior orbital vein (SOV), superior petrosal sinus, inferior petrosal sinus, and pterygoid plexus. We thought the fistula would occlude by intra-aneurysmal embolization, but we had no confidence of tight packing of the aneurysm since the aneurismal neck was relatively wide. So, we embolized the venous side of the shunting fistula and then the dome of the aneurysm with GDCs. Immediately after the operation, her symptoms and signs were ameliorated, and complete occlusion of the CCF was observed on long-term follow-up. We suggest selective intrafistula and intra-aneurysmal embolization with GDCs as an alternative method of treatment of idiopathic CCF originating from aneurysmal rupture of the intra-cavernous carotid artery.
idiopathic CCF; aneurysm; GDC
Budd-Chiari syndrome refers to hepatic pathology secondary to diminished venous outflow, most commonly associated with venothrombotic disease. Clinically, patients with Budd-Chiari present with hepatomegaly, ascites, abdominal distension, and pain. On imaging, Budd-Chiari syndrome is hallmarked by occluded IVC and or hepatic veins, caudate lobe enlargement, heterogeneous liver enhancement, intrahepatic collaterals, and hypervascular nodules. Etiopathological factors for Budd-Chiari syndrome include several systemic thrombotic and nonthrombotic conditions that can cause venous outflow obstruction at hepatic veins and/or IVC. While the transjugular intrahepatic portosystemic shunt (TIPS) is used as a treatment option for Budd-Chiari syndrome, Budd-Chiari syndrome is not a well-known complication of TIPS procedure. We report a case of Budd-Chiari syndrome that occurred in a transplanted cirrhotic liver from malpositioned proximal portion of the TIPS in IVC causing occlusion of the ostia of hepatic veins which was subsequently diagnosed on contrast-enhanced CT.
To determine the feasibility of transcaval transjugular intrahepatic portosystemic shunt (TIPS) in patients with occluded previous TIPS.
Materials and Methods
Between February 1996 and December 2000 we performed five transcaval TIPS procedures in four patients with recurrent gastric cardiac variceal bleeding. All four had occluded TIPS, which was between the hepatic and portal vein. The interval between initial TIPS placement and revisional procedures with transcaval TIPS varied between three and 31 months; one patient underwent transcaval TIPS twice, with a 31-month interval. After revision of the occluded shunt failed, direct cavoportal puncture at the retrohepatic segment of the IVC was attempted.
Transcaval TIPS placement was technically successful in all cases. In three, tractography revealed slight leakage of contrast materials into hepatic subcapsular or subdiaphragmatic pericaval space. There was no evidence of propagation of extravasated contrast materials through the retroperitoneal space or spillage into the peritoneal space. After the tract was dilated by a bare stent, no patient experienced trans-stent bleeding and no serious procedure-related complications occurred. After successful shunt creation, variceal bleeding ceased in all patients.
Transcaval TIPS placement is an effective and safe alternative treatment in patients with occluded previous TIPS and no hepatic veins suitable for new TIPS.
Hypertension, portal; Interventional procedures, complications; Shunts, portosystemic
Congenital intrahepatic portosystemic venous shunts are rare vascular malformations often associated with severe complications. We describe a term male infant with Down syndrome with high output heart failure secondary to a congenital arterial to portal venous fistula that was diagnosed by Doppler ultrasound. Percutaneous embolizations of the left hepatic vein, portal vein, and communicating fistulas were performed without complications, resulting in clinical improvement. A subsequent hepatic ultrasound demonstrated resolution of the pathologic fistulous communication and shunting effects.
To anticipate the hepatic vascular response to portacaval anastomosis, we studied portal pressure during diversion of portal blood through a temporary extracorporeal umbilical vein to saphenous vein shunt. The relationship of portal pressure to shunted flow was approximately linear. In five schistosomiasis patients (controls) portal diversion to 1,250 ml/min gave portal pressure-shunted flow curve slopes ranging from 0.13 to 0.57 cm water/100 ml per min (0.31±0.18, mean±SD). In 17 cirrhotic patients with portal hypertension a continuum of slopes was observed from within mean±2 SD of control (type A) to larger slopes (type B) indicating failure of portal pressure regulation. When portal flow was augmented by shunting from saphenous vein to portal vein, cirrhotic patients who had slopes less than mean±2 SD of controls during diversion (type A) exhibited a compliant system with small increases in portal pressure, whereas type B patients had significantly greater pressure increases. Selective investigations suggested that changes in portal pressure provoked compensatory changes in hepatic arterial blood flow that tended to maintain portal pressure at a set point. Type B patients demonstrated failure of this mechanism to varying degrees.
After end-to-side portacaval shunt, seven type A cirrhotic patients maintained residual intrahepatic venous pressure unchanged from prior portal pressure, whereas six type B patients had a significant decrease. Residual intrahepatic venous pressure was measured after portacaval shunt in 40 cirrhotic patients who were followed for as long as 9 yr (median survival 4.0 yr). The 13 patients who developed chronic encephalopathy had significantly lower pressure (21.1±4.4 cm, mean±SD) and shorter survival (median 0.6 yr) than the other 27 patients (32.6±5.3 cm, 5.0 yr). The preoperative estimation of portal pressure-diverted portal flow curve slope anticipates the hepatic vascular response to portacaval anastomosis and identifies a group of patients in whom loss of portal blood flow results in a low residual intrahepatic venous pressure that is associated with early death and chronic encephalopathy.
Transjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal hypertension. Although the primary patency of TIPS has been greatly improved due to the clinical application of cover stent-grafts, the long-term patency is still suboptimal. This study was to investigate the feasibility of using magnetic resonance imaging (MRI)-monitored intra-shunt local agent delivery of motexafin gadolinium (MGd) into shunt-vein walls of TIPS. This new technique aimed to ultimately inhibit shuntstenosis of TIPS.
Human umbilical vein smooth muscle cells (SMCs) were incubated with various concentrations of MGd, and then examed by confocal microscopy and T1-map MRI. In addition, the proliferation of MGd-treated cells was evaluated. For in vivo validation, seventeen pigs underwent TIPS. Before placement of the stent, an MGd/trypan-blue mixture was locally delivered, via a microporous balloon, into eleven shunt-hepatic vein walls under dynamic MRI monitoring, while trypan-blue only was locally delivered into six shunt-hepatic vein walls as serve as controls. T1-weighted MRI of the shunt-vein walls was achieved before- and at different time points after agent injections. Contrast-to-noise ratio (CNR) of the shunt-vein wall at each time-point was measured. Shunts were harvested for subsequent histology confirmation.
In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well. Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology.
Results of this study indicate that MRI-monitored intra-shunt local MGd delivery is feasible and MGd functions as a potential therapeutic agent to inhibit the proliferation of SMCs, which may open alternative avenues to improve the long-term patency of TIPS.
Congenital portosystemic shunts are developmental anomalies of the splanchnic vascular system that cause portal blood to bypass the liver. Large-breed dogs are predisposed for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs for extrahepatic portosystemic shunts (EHPSS). While the phenotype resulting from portal bypass of the liver of the two types of shunt is identical, the genotype and molecular pathways involved are probably different. The aim of this study was to gain insight into the pathways involved in the different types of portosystemic shunting. Microarray analysis of mRNA expression in liver tissue from dogs with EHPSS and IHPSS revealed that the expression of 26 genes was altered in either IHPSS or EHPSS samples compared with that in liver samples from control dogs. Quantitative real-time PCR of these genes in 14 IHPSS, 17 EHPSS, and 8 control liver samples revealed a significant differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry and Western blotting confirmed an increased expression of VCAM1 in IHPSS but its absence in EHPSS, an increased WEE1 expression in IHPSS but not in EHPSS, and a decreased expression of CCBL1 in both shunt types. Regarding their physiologic functions, these findings may indicate a causative role for VCAM1 in IHPSS and WEE1 for IHPSS. CCBL1 could be an interesting candidate to study not yet elucidated aspects in the pathophysiology of hepatic encephalopathy.
Congenital disorders of the hepatic portal vasculature are rare in man but occur frequently in certain dog breeds. In dogs, there are two main subtypes: intrahepatic portosystemic shunts, which are considered to stem from defective closure of the embryonic ductus venosus, and extrahepatic shunts, which connect the splanchnic vascular system with the vena cava or vena azygos. Both subtypes result in nearly complete bypass of the liver by the portal blood flow. In both subtypes the development of the smaller branches of the portal vein tree in the liver is impaired and terminal branches delivering portal blood to the liver lobules are often lacking. The clinical signs are due to poor liver growth, development, and function. Patency of the ductus venosus seems to be a digenic trait in Irish wolfhounds, whereas Cairn terriers with extrahepatic portosystemic shunts display a more complex inheritance. The genes involved in these disorders cannot be identified with the sporadic human cases, but in dogs, the genome-wide study of the extrahepatic form is at an advanced stage. The canine disease may lead to the identification of novel genes and pathways cooperating in growth and development of the hepatic portal vein tree. The same pathways likely regulate the development of the vascular system of regenerating livers during liver diseases such as hepatitis and cirrhosis. Therefore, the identification of these molecular pathways may provide a basis for future proregenerative intervention.
Percutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke is an alternative to medical therapy. There is still debate on different outcome for each currently available device. The impact of residual shunting after PFO-clo- sure on recurrent arterial embolism is unknown.
(i) To evaluate the prevalence of residual interatrial shunting after device- closure of PFO, (ii) to identify risk factors predicting residual interatrial shunting after device implantation, and (iii) to investigate the outcome of patients after PFO-closure during long- term follow- up (FU).
Methods and results
Between 2000- 2005 PFO-closure was performed in 124 patients using four different devices: Amplatzer PFO-(n = 52), CardioSeal (n = 33), Helex (n = 23) and Premere (n = 16) occluder. All patients underwent serial contrast-enhanced transesophageal echocardiography (TEE) for 24 months after PFO- closure; clinical FU was at minimum 5 years up to 9.75 years (mean 6.67 ± 1.31 years). Overall-closure rate was 87% at 2 years, device-specific closure time curves differed significantly (p-logrank = 0.003). Independent risk factors for residual-shunting were implantation of a Helex occluder (hazard ratio [HR] 12.6, 95% confidence interval [CI] 2.6- 57.4, p = 0.002), PFO- canal- lengths (HR 1.2, 95%CI 1.1- 1.3, p = 0.004) and extend of atrial-septal-aneurysm (HR 1.1, 95%CI 0.9- 1.3; p = 0.05). 4 (3.2%) arterial embolic events occurred during a FU-period of 817.2 patient-years, actuarial annual thromboembolic-risk was 0.49%. All ischemic events were not related to residual PFO-shunting or device-related thrombus- formation.
Success rates of PFO- closure are mainly dependent on occluder-type, extend of concomitant atrial-septum-aneurysm and PFO-canal- length. Importantly, residual shunting after PFO-closure was not associated with recurrence of arterial embolism during long-term follow-up.
A 7-month-old girl with failure to thrive, who, on clinical and diagnostic evaluation [echocardiography & CT angiography] to rule out congenital heart disease, revealed a rare vascular anomaly called systemic artery to pulmonary venous fistula. In our case, there was dual abnormal supply to the entire left lung as1 anomalous supply by normal systemic artery [internal mammary artery]2 and an aberrant feeder vessel from the abdominal aorta. Left Lung had normal bronchial connections and normal pulmonary vasculature. The fistula drained through the pulmonary veins to the left atrium leading to ‘left–left shunt’. Percutaneous intervention in two stages was performed using Amplatzer vascular plugs and coil embolization to close them successfully. The patient gained significant weight in follow up with other normal developmental and mental milestones.
Congenital AV fistula; Sequestration of lung
Multiple intrahepatic portosystemic shunt (IPSS) without portal hypertension, now thought to be congenital in origin, is very rare. The presence of IPSS, unlike other congenital diseases, may not be recognized for several decades due to the time it takes to develop hepatic encephalopathy. In this article, we report an autopsy case of an 80-year-old Japanese woman with a one-month history of hyperammonemic encephalopathy. Radiological examination of the liver revealed some abnormal connections between the branches of the portal veins and the hepatic veins, but the cause of the aberrant blood flow was not found. The cause of death was extensive cerebral infarction due to thromboembolism. At postmortem examination, multiple anomalous blood vessels were identified histologically in both lobes of the non-cirrhotic liver. In comparison with the few similar cases existing in the literature, this case should be diagnosed as congenital IPSS. To our knowledge, this is the first detailed histological study of IPSS, as several autopsy case reports exist but their histological descriptions are poor. Unlike past reports, the shunt vessels were accompanied by clear elastic lamellae that were microscopically observed. In addition to shunt vessels, septal fibrosis, disorder of hepatic acinar structure, and sinusoidal dilatation and capillarization were observed in the liver. We suggest that these histological modifications observed in the circumference of the shunt vessels acted as secondary regenerative/hyperplastic changes based on blood-flow imbalance caused by the IPSS.
Congenital intrahepatic portosystemic shunt; hepatic encephalopathy; autopsy