Addition of n-butyl cyanoacrylate to classic transarterial chemoembolization may improve the radiological response in patients with hepatocellular carcinoma

OBJECTIVE: Transarterial chemoembolization is the treatment of choice for intermediate-stage hepatocellular carcinoma. However, there are no clear data supporting transarterial chemoembolization vs . transarterial embolization or regarding the best chemotherapeutic agent, which may suggest a preponderant role of ischemia over chemotherapeutic action. This study sought to evaluate the radiological response and outcome of transarterial chemoembolization modified by n-butyl cyanoacrylate addition compared to conventional transarterial chemoembolization in hepatocellular carcinoma patients. MATERIALS AND METHODS: A retrospective review identified forty-seven patients who underwent modified chemoembolization and thirty-three who underwent conventional chemoembolization between June 2006 and December 2011. The radiological response was reassessed using the modified Response Evaluation Criteria in Solid Tumors. The sustained complete response, time to progression and overall survival rates were also analyzed. RESULTS: Complete response rates were significantly higher in patients who had undergone modified chemoembolization compared to those who had undergone conventional treatment (61.7% and 24.3%, respectively; p <0.001). The rate of sustained complete response was significantly higher in the modified chemoembolization group compared to the conventional chemoembolization group (median of 236 and 37 days, respectively; p <0.001). Time to progression was significantly higher in the modified chemoembolization group compared to the conventional chemoembolization group (median of 424 and 201 days, respectively; p =0.042). Overall survival rates revealed no difference between patients who received modified chemoembolization and conventional chemoembolization (median of 483 and 399 days, respectively; p =0.316). CONCLUSION: Transarterial chemoembolization modified by n-butyl cyanoacrylate addition was superior to conventional transarterial chemoembolization in terms of the radiological response in the first imaging control. Although the sustained complete response and time to progression rates were higher for the modified chemoembolization group, no differences in overall survival rates were observed.

Can proton pump inhibitors reduce rebleeding following Histoacryl sclerotherapy for gastric variceal hemorrhage?

BACKGROUND/AIMS: To evaluate the efficacy of proton pump inhibitors (PPIs) in reducing rebleeding and bleeding-related death rates after endoscopic gastric variceal obliteration (GVO) using N-butyl-2-cyanoacrylate (NBC). METHODS: This study enrolled 341 patients who were consecutively diagnosed with and treated for bleeding gastric varices. The patients were divided into PPI and non-PPI groups, and their endoscopic findings, initial hemostasis outcomes, rebleeding and bleeding-related death rates, and treatment-related complications were analyzed. RESULTS: The rate of initial hemostasis was 97.1%. rebleeding occurred in 2.2% of patients within 2 weeks, 3.9% of patients within 4 weeks, 18.9% of patients within 6 months, and 27.6% of patients within 12 months of the GVO procedure. A previous history of variceal bleeding (relative risk [RR], 1.955; 95% confidence interval [CI], 1.263 to 3.028; p = 0.003) and use of PPIs (RR, 0.554; 95% CI, 0.352 to 0.873; p = 0.011) were associated with rebleeding. Child-Pugh class C (RR, 10.914; 95% CI, 4.032 to 29.541; p < 0.001), failure of initial hemostasis (RR, 13.329; 95% CI, 2.795 to 63.556; p = 0.001), and the presence of red-colored concomitant esophageal varices (RR, 4.096; 95% CI, 1.320 to 12.713; p = 0.015) were associated with bleeding-related death. CONCLUSIONS: The prophylactic use of PPIs reduces rebleeding after GVO using NBC in patients with gastric variceal hemorrhage. However, prophylactic use of PPIs does not reduce bleeding-related death.

Hepatoduodenal fistula formation following transcatheter arterial chemoembolization and radiotherapy for hepatocellular carcinoma: treatment with endoscopic Histoacryl injection

A 71-year-old male patient was readmitted to our hospital 1 month after discharge because of relapse of abdominal pain. He had been diagnosed with hepatocellular carcinoma (HCC) 1 year prior and had undergone repeated transcatheter arterial chemoembolization and radiotherapy. During the last hospitalization, he was diagnosed with a liver abscess complicated by previous treatments for HCC and was treated with intravenous antibiotics and abscess aspiration. Follow-up abdominal computed tomography revealed a liver abscess with a duodenal fistula, which was successfully treated with endoscopic Histoacryl injection into the fistula. Liver abscesses with duodenal fistulas rarely occur, but they are intractable and possibly fatal in patients with HCC. In the literature, they have frequently been managed only with abscess treatment without fistula management. We herein report the first case of a patient with a liver abscess complicated by a fistula between the duodenum and the abscess, which was treated with endoscopic Histoacryl injection.

Treatment of Hemodialysis Vascular Access Rupture Irresponsive to Prolonged Balloon Tamponade: Retrospective Evaluation of the Effectiveness of N-Butyl Cyanoacrylate Seal-Off Technique

OBJECTIVE: The current study retrospectively evaluated whether the percutaneous N-butyl cyanoacrylate (NBCA) seal-off technique is an effective treatment for controlling the angioplasty-related ruptures, which are irresponsive to prolonged balloon tamponade, during interventions for failed or failing hemodialysis vascular accesses. MATERIALS AND METHODS: We reviewed 1588 interventions performed during a 2-year period for dysfunction and/or failed hemodialysis vascular access sites in 1569 patients. For the angioplasty-related ruptures, which could not be controlled with repeated prolonged balloon tamponade, the rupture sites were sealed off with an injection of a glue mixture (NBCA and lipiodol), via a needle/needle sheath to the rupture site, under a sonographic guidance. Technical success rate, complications and clinical success rate were reported. The post-seal-off primary and secondary functional patency rates were calculated by a survival analysis with the Kaplan-Meier method. RESULTS: Twenty ruptures irresponsive to prolonged balloon tamponade occurred in 1588 interventions (1.3%). Two technical failures were noted; one was salvaged with a bailout stent-graft insertion and the other was lost after access embolization. Eighteen accesses (90.0%) were salvaged with the seal-off technique; of them, 16 ruptures were completely sealed off, and two lesions were controlled as acute pseudoaneurysms. Acute pseudoaneurysms were corrected with stentgraft insertion in one patient, and access ligation in the other. The most significant complication during the follow-up was delayed pseudoaneurysm, which occurred in 43.8% (7 of 16) of the completely sealed off accesses. Delayed pseudoaneurysms were treated with surgical revision (n = 2), access ligation (n = 2) and observation (n = 3). During the follow-up, despite the presence of pseudoaneurysms (acute = 1, delayed = 7), a high clinical success rate of 94.4% (17 of 18) was achieved, and they were utilized for hemodialysis at the mean of 411.0 days. The post-seal-off primary patency vs. secondary patency at 90, 180 and 360 days were 66.7 +/- 11.1% vs. 94.4 +/- 5.4%; 33.3 +/- 11.1% vs. 83.3 +/- 8.8%; and 13.3 +/- 8.5% vs. 63.3 +/- 12.1%, respectively. CONCLUSION: Our results suggest that the NBCA seal-off technique is effective for immediate control of a venous rupture irresponsive to prolonged balloon tamponade, during interventions for hemodialysis accesses. Both high technical and clinical success rates can be achieved. However, the treatment is not durable, and about 40% of the completely sealed off accesses are associated with developed delayed pseudoaneurysms in a 2-month of follow-up. Further repair of the vascular tear site, with surgery or stent-graft insertion, is often necessary.

Rat Model of Hindlimb Ischemia Induced via Embolization with Polyvinyl Alcohol and N-Butyl Cyanoacrylate

OBJECTIVE: To investigate the feasibility of a rat model on hindlimb ischemia induced by embolization from the administration of polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA). MATERIALS AND METHODS: Unilateral hindlimb ischemia was induced by embolization with NBCA (n = 4), PVA (n = 4) or surgical excision (n = 4) in a total of 12 Sprague-Dawley rats. On days 0, 7 and 14, the time-of-flight magnetic resonance angiography (TOF-MRA) and enhanced MRI were obtained as scheduled by using a 3T-MR scanner. The clinical ischemic index, volume change and degree of muscle necrosis observed on the enhanced MRI in the ischemic hindlimb were being compared among three groups using the analysis of variance. Vascular patency on TOF-MRA was evaluated and correlated with angiographic findings when using an inter-rater agreement test. RESULTS: There was a technical success rate of 100% for both the embolization and surgery groups. The clinical ischemic index did not significantly differ. On day 7, the ratios of the muscular infarctions were 0.436, 0.173 and 0 at thigh levels and 0.503, 0.337 and 0 at calf levels for the NBCA, PVA and surgery groups, respectively. In addition, the embolization group presented increased volume and then decreased volume on days 7 and 14, respectively. The surgery group presented a gradual volume decrease. Good correlation was shown between the TOF-MRA and angiographic findings (kappa value of 0.795). CONCLUSION: The examined hindlimb ischemia model using embolization with NBCA and PVA particles in rats is a feasible model for further research, and muscle necrosis was evident as compared with the surgical model.

Percutaneous Transabdominal Approach for the Treatment of Endoleaks after Endovascular Repair of Infrarenal Abdominal Aortic Aneurysm

OBJECTIVE: The purpose of this study was to evaluate the technical feasibility and clinical efficacy of percutaneous transabdominal treatment of endoleaks after endovascular aneurysm repair. MATERIALS AND METHODS: Between 2000 and 2007, six patients with type I (n = 4) or II (n = 2) endoleaks were treated by the percutaneous transabdominal approach using embolization with N-butyl cyanoacrylate with or without coils. Five patients underwent a single session and one patient had two sessions of embolization. The median time between aneurysm repair and endoleak treatment was 25.5 months (range: 0-84 months). Follow-up CT images were evaluated for changes in the size and shape of the aneurysm sac and presence or resolution of endoleaks. The median follow-up after endoleak treatment was 16.4 months (range: 0-37 months) RESULTS: Technical success was achieved in all six patients. Clinical success was achieved in four patients with complete resolution of the endoleak confirmed by follow-up CT. Clinical failure was observed in two patients. One eventually underwent surgical conversion, and the other was lost to follow-up. There were no procedure-related complications. CONCLUSION: The percutaneous transabdominal approach for the treatment of type I or II endoleaks, after endovascular aneurysm repair, is an alternative method when conventional endovascular methods have failed.

Transcatheter Arterial Embolization of Arterial Esophageal Bleeding with the Use of N-Butyl Cyanoacrylate

OBJECTIVE: To evaluate the clinical efficacy and safety of a transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) for the treatment of arterial esophageal bleeding. MATERIALS AND METHODS:Between August 2000 and April 2008, five patients diagnosed with arterial esophageal bleeding by conventional angiography, CT-angiography or endoscopy, underwent a TAE with NBCA. We mixed NBCA with iodized oil at ratios of 1:1 to 1:4 to supply radiopacity and achieve a proper polymerization time. After embolization, we evaluated the angiographic and clinical success, recurrent bleeding, and procedure-related complications. RESULTS: The bleeding esophageal artery directly originated from the aorta in four patients and from the left inferior phrenic artery in one patient. Although four patients had an underlying coagulopathy at the time of the TAE, angiographic and clinical success was achieved in all five patients. In addition, no procedure-related complications such as esophageal infarction were observed during this study. CONCLUSION: NBCA can be an effective and feasible embolic agent in patients with active arterial esophageal bleeding, even with pre-existing coagulopathy.

Cyst Ablation Using a Mixture of N-Butyl Cyanoacrylate and Iodized Oil in Patients with Autosomal Dominant Polycystic Kidney Disease: the Long-Term Results

OBJECTIVE: We wanted to assess the long-term results of cyst ablation with using N-butyl cyanoacrylate (NBCA) and iodized oil in patients with autosomal dominant polycystic kidney disease (ADPKD) and symptomatic cysts. MATERIALS AND METHODS:Cyst ablation using a mixture of NBCA and iodized oil was performed in 99 cysts from 21 patients who had such symptoms as abdominal distension and pain. The collapse or reaccumulation of the ablated cysts after the procedure was assessed during the follow-up period of 36 to 90 months. The treatment effects, including symptom relief, and the clinical data such as the blood pressure and serum creatinine levels were also assessed, together with the complications. RESULTS: The procedure was technically successful in all 99 cysts from the 21 patients. Any procedure-related significant complications were not detected. Seventy-seven of 99 cysts (78%) were successfully collapsed on the follow-up CT. Twenty-two cysts showed reaccumulation during long-term follow-up period. The clinical symptoms were relieved in 17 of the 21 patients (76%). Four of 12 patients (33%) with hypertension and two of six patients (33%) with azotemia were improved. End stage renal disease (ESRD) occurred in six of the 21 patients (28%) during the follow-up period. The mean age of ESRD in our patients was 57 years. The mean time interval for the development of ESRD was 19 months. CONCLUSION: Ablation using a mixture of NBCA and iodized oil may be an effective, safe method for obtaining symptom relief in patients with ADPKD.

Percutaneous Transportal Sclerotherapy with N-Butyl-2-Cyanoacrylate for Gastric Varices: Technique and Clinical Efficacy

OBJECTIVE: This study was deigned to evaluate the technique and clinical efficacy of the use of percutaneous transportal sclerotherapy with N-butyl-2-cyanoacrylate (NBCA) for patients with gastric varices. MATERIALS AND METHODS: Seven patients were treated by transportal sclerotherapy with the use of NBCA. For transportal sclerotherapy, portal vein catheterization was performed with a 6-Fr sheath by the transhepatic approach. A 5-Fr catheter was introduced into the afferent gastric vein and a microcatheter was advanced through the 5-Fr catheter into the varices. NBCA was injected through the microcatheter in the varices by use of the continuous single-column injection technique. After the procedure, postcontrast computed tomography (CT) was performed on the next day and then every six months. Gastroendoscopy was performed at one week, three months, and then every six months after the procedure. RESULTS: The technical success rate of the procedure was 88%. In six patients, gastric varices were successfully obliterated with 1-8 mL (mean, 5.4 mL) of a NBCA-Lipiodol mixture injected via a microcatheter. No complications related to the procedure were encountered. As seen on the follow-up endoscopy and CT imaging performed after six months, the presence of gastric varcies was not seen in any of the patients after treatment with the NBCA-Lipiodol mixture and the use of microcoils. Recurrence of gastric varices was not observed during the follow-up period. Worsening of esophageal varices occurred in four patients after transportal sclerotherapy. The serum albumin level increased, the ammonia level decreased and the prothrombin time increased at six months after the procedure (p < 0.05). CONCLUSION: Percutaneous transportal sclerotherapy with NBCA is useful to obliterate gastric varices if it is not possible to perform balloon-occluded retrograde transvenous obliteration.

Ethanol Embolotherapy of Pelvic Arteriovenous Malformations: an Initial Experience

OBJECTIVE: We retrospectively assessed the results of performing ethanol embolization for pelvis arteriovenous malformations (AVMs). MATERIALS AND METHODS: During the past 10 years, eight patients (8 females, age range: 27-52 years) with AVMs in the pelvic wall (n = 3) and uterus (n = 5) underwent staged ethanol embolizations (range: 1-5, mean: 2.5) under general anesthesia. Ethanol embolization was performed by the use of the transcatheter and/or direct puncture techniques. Clinical follow-up was performed for all of the patients, and imaging follow-up was available for seven patients. The therapeutic outcomes were established by evaluating the clinical outcome of the signs and symptoms, as well as the degree of devascularization observed on post-procedural angiography. RESULTS: During the 20 sessions of ethanol embolization, the solitary transarterial approach was used 14 times, the transvenous approach was used three times and direct puncture was used once. For two patients, the transarterial and transvenous or direct puncture approaches were used together in one session. For four patients, ethanol and coils were used as embolic agents, and n-butyl cyanoacrylate (NBCA) and ethanol were used in one patient. Seven (88%) of eight patients were cured of their AVMs and one patient (12%) displayed improvement. Major complications were seen in two patients (25%). CONCLUSION: Ethanol embolization is effective for the treatment of pelvic arteriovenous malformations, though there is a chance of a major complication.

Validity of microporous polysaccharide hemispheres as a hemostatic agent in hepatic injuries: an experimental study in rats

INTRODUCTION: In the treatment of hepatic injuries, there is not always adequate and secure hemostasis. A hepatic biopsy is indispensable in the evolution of focal or diffuse liver cell disease, being necessary for candidates for liver transplant and post-transplant treatment. Many patients suffer blood clotting that increases the risk of bleeding. For this reason, it is necessary to seek for substances capable of bringing about hemostasis quickly and effectively. PURPOSE: The aim of this study was to recognize the validity of the use of microporous polysaccharide hemispheres (MPH) as a hemostatic agent for hepatic injuries. METHODS: Thirty Wistar rats were used, split into three groups. Under anaesthetic, a laparoptomy was done and resulted in a standard liver injury that was treated in Group A with MPH, in Group B with n-butyl-2-cyanoacrylate and in Group C with fibrin adhesive. Immediate hemostasis, delayed bleeding and histological evolution were timed. RESULTS: The MPH took on average six minutes to promote hemostasis and also resulted in re-bleeding, which required reapplication; the n-butyl-2-cyanoacrylate took twenty seconds and the fibrin adhesive took one minute. The cyanoacrylate resulted in more intense adherence. The three adhesives mainly showed a chronic inflammatory reaction. The injuries treated with cyanoacrylate showed a larger area of injury (p=0,0164). The density of the collagen was similar in all groups. CONCLUSION: The MPH, despite achieving hemostasis, proved to be no more favorable than n-butyl-cyanoacrylate and the fibrin adhesive, the latter resulting in the lowest tissue reaction.

INTRODUÇÃO: No tratamento de lesões hepáticas nem sempre se tem hemostasia adequada e segura. Biópsia hepática é indispensável na evolução de doença hepato-celular difusa ou focal sendo necessária para candidatos à transplante hepático e para acompanhamento pós-transplante. Muitos doentes apresentam coagulopatias que aumentam os riscos de sangramento. Daí a necessidade de se procurar substâncias capazes de promover a hemostasia de forma rápida e efetiva. OBJETIVO: O objetivo deste estudo foi reconhecer a validade do uso de hemosferas microporosas de polissacarídeos (MPH) como agente hemostático para lesões hepáticas. MÉTODOS: Utilizaram-se 30 ratos Wistar distribuídos em três grupos. Sob anestesia, fez-se uma laparotomia e produziu-se um ferimento hepático padrão que foi tratado no grupo A com MPH, no grupo B, com n-butil-2-cianoacrilato e no grupo C com adesivo de fibrina. Cronometrou-se o tempo para a obtenção da hemostasia imediata, a existência de sangramento tardio e a evolução histológica. RESULTADOS: O MPH levou, em média, seis minutos para promover a hemostasia e apresentou re-sangramento exigindo reaplicação, o n-butil-2-cianoacrlato, 20 segundos e o adesivo de fibrina, um minuto. O cianoacrilato promoveu aderências mais intensas. Os três adesivos determinaram principalmente reação inflamatória do tipo crônico. As feridas tratadas com cianoacrilato apresentaram maior área de lesão (p=0,0164). A densidade do colágeno foi semelhante entre os grupos. CONCLUSÃO: O MPH, embora tenha conseguido hemostasia, não se mostrou mais favorável do que o n-butil-2-cianoacrilato e o adesivo de fibrina sendo que este último promoveu a menor reação tecidual.

Long-term Results of Endoscopic Histoacryl(R) (N-butyl-2-cyanoacrylate) Injection for Treatment of Gastric Varices : A 10-year Experience / 대한소화기학회지

BACKGROUND/AIMS: Gastric variceal bleeding is an infrequent but serious complication of portal hypertension. Endoscopic injection of Histoacryl(R) (N-butyl-2-cyanoacrylate) has been approved as an effective treatment for gastric variceal bleeding. The aim of this study was to evaluate the long-term efficacy and safety of the endoscopic injection of Histoacryl(R) for the treatment of gastric varices. METHODS: Between January 1994 and January 2005, eighty-five patients with gastric varices received endoscopic injections of Histoacryl(R) . Among these 85 patients, 65 received the procedure within 1 week after gastric variceal bleeding, and 13 received as a prophylactic procedure. According to the Sarin classification, 32 patients were GOV1 and 53 were GOV2. Most of the varices were large (F2 or F3, 75 patients). The average volume of Histoacryl(R) per each session was 1.43 ml. Among 85 patients, 72 patients were followed-up and the median duration was 24.5 months. RESULTS: The rate of initial hemostasis was 98.6% and recurrent bleeding occurred in 29.2% (21 of 72). When rebleeding occurred, 76.2% was within 1 year after the initial injection. Treatment failure-related mortality rate was 1.4% (1 of 85). Twenty-seven patients died, mostly due to hepatocelluar carcinoma or liver failure. Two patients experienced pulmonary embolism and one experienced splenic infarction. They recovered without specific treatment. Rebleeding rate had a tendency to increase in patients with hepatocelluar carcinoma (p=0.051) and GOV2 (p=0.061). CONCLUSIONS: Histoacryl(R) injection therapy is a effective treatment method for gastric varices with high initial hemostasis rate and low major complications.

Therapeutic Effect of the Endoscopic N-butyl-2-cyanoacrylate Injection for Acute Esophagogastric Variceal Bleeding: Comparison with Transjugular Intrahepatic Portosystemic Shunt / 대한소화기학회지

BACKGROUND/AIMS: Though endoscopic therapies such as variceal ligation and sclerotherapy has been performed, bleeding from the large esophageal and gastric varices still poses significant risk of death. Decrease of portal pressure by TIPS (transjugular intrahepatic portosystemic shunt) or surgical shunt was indicated as cause of failure of endoscopic therapies. Treatment of N-butyl-2-cyanoacrylate has been especially effective for gastric variceal bleeding, but comparison with other treatments had not been reported yet. In this study, the effect of cyanoacrylate injection therapy was cross-examined with the result of TIPS in acute esophagogastric variceal bleedings. METHODS: From April 1995 to June 2002, endoscopic cyanoacrylate injection therapy (43 cases) and TIPS (63 cases) were performed in our hospital. Each group was analysed regarding their clinical results including initial hemostasis rate, rebleeding rate, survival duration, mortality and morbidity. RESULTS: Initial hemostasis rate was 95.3% in cyanoacrylate group and 92.1% in TIPS group. Cumulative probability of rebleeding was not different between two groups. Overall complication rates associated with the procedure were 50.8% in TIPS group and 9.3% in cyanoacrylate group. There was no significant difference between two groups in their survival rates. CONCLUSIONS: Cyanoacrylate injection therapy was relatively safe, and has comparable results with TIPS for uncontrollable and severe esophagogastric variceal bleedings.