Safety and efficacy of modified endoscopic ultrasound-guided selective N-butyl-2-cyanoacrylate injections for gastric variceal hemorrhage in left-sided portal hypertension

BACKGROUND Gastric variceal hemorrhage is one of the primary manifestations of left-sided portal hypertension(LSPH).The hemorrhage is fatal and requires safe and effective interventions.AIM To evaluate the clinical safety and efficacy of modified endoscopic ultrasound(EUS)-guided selective N-butyl-2-cyanoacrylate(NBC)injections for gastric variceal hemorrhage in LSPH.METHODS A retrospective observational study of patients with LSPH-induced gastric variceal hemorrhage was conducted.Preoperative EUS evaluations were performed.Enrolled patients were divided into modified and conventional groups according to the NBC injection technique.The final selection of NBC injection technique depended on the patients’preferences and clinical status.The technical and clinical success rates,operation time,NBC doses,perioperative complications,postoperative hospital stay,and recurrent bleeding rates were analyzed,respectively.RESULTS A total of 27 patients were enrolled.No statistically significant differences were observed between the two groups regarding baseline characteristics.In comparison to patients in the conventional group,patients in the modified group demonstrated significantly reduced NBC doses(2.0±0.6 mL vs 3.1±1.0 mL;P=0.004)and increased endoscopic operation time(71.9±11.9 min vs 22.5±6.7 min;P<0.001).Meanwhile,the two groups had no significant difference in the technical and clinical success rates,perioperative complications,postoperative hospital stay,and recurrent bleeding rates.CONCLUSION Modified EUS-guided selective NBC injections demonstrated safety and efficacy for LSPH-induced gastric variceal hemorrhage,with advantages of reduced injection dose and no radiation risk.Drawbacks were time consumption and technical challenge.

Long-term result of endoscopic Histoacryl （N-butyl-2-cyanoacrylate）injection for treatment of gastric varices

AIM:To evaluate the long-term efficacy and safety of endoscopic obliteration with Histoacryl for treatment of gastric variceal bleeding and prophylaxis.METHODS:Between January 1994 and March 2010 at SoonChunHyang University Hospital,a total of 127 patients with gastric varices received Histoacryl injections endoscopically.One hundred patients underwent endoscopic Histoacryl injections because of variceal bleeding,the other 27 patients received such injections as a prophylactic procedure.RESULTS:According to Sarin classification,56 patients were GOV1,61 patients were GOV2 and 10 patients were IGV.Most of the varices were large(F2 or F3,111 patients).The average volume of Histoacryl per each session was 1.7±1.3 cc and mean number of sessions was 1.3±0.6.(1 session-98 patients,2 sessions-25 patients,≥3 sessions-4 patients).Twenty-seven patients with high risk of bleeding(large or fundal or RCS+or Child C) received Histoacryl injection as a primary prophylactic procedure.In these patients,hepatitis B virus was the major etiology of cirrhosis,25 patients showed GOV1 or 2(92.6%)and F2 or F3 accounted for 88.9%(n=24).The rate of initial hemostasis was 98.4%and recurrent bleeding within one year occurred in 18.1%of patients.Successful hemostasis during episodes of rebleeding was achieved in 73.9%of cases.Median survival was 50 mo (95%CI 30.5-69.5).Major complications occurred in 4 patients(3.1%).The rebleeding rate in patients with hepatocellular carcinoma or GOV2 was higher than in those with other conditions.None of the 27 subjects who were treated prophylactically experienced treatment-related complications.Cumulative survival rates of the 127 patients at 6 mo,1,3,and 5 years were 92.1%,84.2%,64.2%,and 45.3%,respectively.The 6 mo cumulative survival rate of the 27 patients treated prophylactically was 75%.CONCLUSION:Histoacryl injection therapy is an effective treatment for gastric varices and also an effective prophylactic treatment of gastric varices which carry high risk of bleeding.

Study of glue extrusion after endoscopic N-butyl-2-cyanoacrylate injection on gastric variceal bleeding

AIM:To investigate glue extrusion after endoscopic N-butyl-2-cyanoacrylate injection on gastric variceal bleeding and to evaluate the long-term efficacy and safety of this therapy.METHODS:A total of 148 cirrhotic patients in our hospital with esophagogastric variceal bleeding(EGVB) were included in this study.N-butyl-2-cyanoacrylate was mixed with lipiodol in a 1:1 ratio and injected as a bolus of 1-3 mL according to variceal size.Patients underwent endoscopic follow-up the next week,fourth week,second month,fourth month,and seventh month after injection and then every 6 mo to determine the cast shape.An abdominal X-ray fi lm and ultrasound or computed tomographic scan were also carried out in order to evaluate the time of variceal disappearance and complete extrusion of the cast.The average follow-up time was 13.1 mo.RESULTS:The instantaneous hemostatic rate was 96.2%.Early re-bleeding after injection in 9 cases(6.2%) was estimated from rejection of adhesive.Late re-bleeding occurred in 12 patients(8.1%) at 2-18 mo.The glue cast was extruded into the lumen within one month in 86.1% of patients and eliminated within one year.Light erosion was seen at the injection position and mucosa edema in the second week.The glue casts were extruded in 18 patients(12.1%) after one week and in 64 patients(42.8%) after two weeks.All kinds of glue clumping shapes and colors on endoscopic examination were observed in 127 patients(86.1%) within one month,including punctiform,globular,pillar and variform.Forty one patients(27.9%) had glue extrusion after 3 mo and 28 patients(28.9%) after six months.The extrusion time was not related to the injection volume of histoacryl.Obliteration was seen in 70.2%(104 cases) endoscopically.The main complication was re-bleeding resulting from extrusion.The prognosis of the patients depended on the severity of the underlying liver disease.CONCLUSION:Endoscopic injection of cyanoacrylate is highly effective for gastric varices bleeding.The glue clump shape is correlated with anatomic structure of vessels.The time of extrusion was not related to dosage of the glue.

N-butyl-2-cyanoacrylate, iso-amyl-2-cyanoacrylate and hypertonic glucose with 72% chromated glycerin in gastric varices

cyanoacrylate and a mixture of 72% chromated glycerinwith hypertonic glucose solution in management ofgastric varices.METHODS： Ninety patients with gastric varicespresented to Endoscopy Unit of Ain Shams UniversityHospital were included. They were randomly allocatedinto three groups; each group included 30 patients treatedwith intravariceal sclerosant injections in biweeklysessions till complete obturation of gastric varices;Group I （n-butyl-2-cyanoacrylate; Histoacryl？）, GroupII （iso-amyl-2-cyanoacrylate; Amcrylate？） and GroupIII （mixture of 72% chromated glycerin; Scleremo？with glucose solution 25%）. All the procedures wereperformed electively without active bleeding. Recruitedpatients were followed up for 3 mo.RESULTS： 26% of Scleremo group had bleeding duringpuncture vs 3.3% in each of the other two groups withsignificant difference, （P 〈 0.05）. None of Scleremogroup had needle obstruction vs 13.3% in each of theother two groups with no significant difference, （P 〉0.05）. Rebleeding occurred in 13.3% of Histoacryl andAmcrylate groups vs 0% in Scleremo group with nosignificant difference. The in hospital mortality was 6.6%in both Histoacryl and Amcrylate groups, while it was0% in Scleremo group with no significant difference. Inthe first and second sessions, the amount of Scleremoneeded for obturation was significantly high, while the amount of Histoacryl was significantly low. Scleremo was the less costly of the two treatments. CONCLUSION： All used sclerosant substances showed efficacy and success in management of gastric varices with no significant differences except in total amount,cost and bleeding during puncture.

Cerebral and splenic infarctions after injection of N-butyl-2-cyanoacrylate in esophageal variceal bleeding

Variceal bleeding is the most serious complication of portal hypertension,and it accounts for approximately one fifth to one third of all deaths in liver cirrhosis patients.Currently,endoscopic treatment remains the predominant method for the prevention and treatment of variceal bleeding.Endoscopic treatments include band ligation and injection sclerotherapy.Injection sclerotherapy with N-butyl-2-cyanoacrylate has been successfully used to treat variceal bleeding.Although injection sclerotherapy with N-butyl-2-cyanoacrylate provides effective treatment for variceal bleeding,injection of N-butyl-2-cyanoacrylate is associated with a variety of complications,including systemic embolization.Herein,we report a case of cerebral and splenic infarctions after the injection of N-butyl-2-cyanoacrylate to treat esophageal variceal bleeding.

Endoscopic management of Dieulafoy's lesion using Isoamyl-2-cyanoacrylate

Dieulafoy's lesion (DL) is a rare but important cause of obscure gastrointestinal bleeding that may be over-looked during diagnostic endoscopy. Mortality rates are similar to those of other causes for gastrointestinal bleeding. Diagnosis by upper endoscopy is the modal-ity of choice during acute bleeding. In the absence of active bleeding, the lesion resembles a raised nipple or visible vessel. There are no guidelines regarding effective selective therapy for DL, when diagnosed, en-doscopist experience is the major determinant of the treatment strategy. Following our strategy, an expert endoscopist with a skilled assistant should have a high rate of successful DL diagnosis when an obscured gas-trointestinal lesion is suspected. Cyanoacryltes com-pounds have been used successfully in management of Gastric varices and DLs. To our knowledge, there have been no previous reports regarding use of isoamyl-2-cyanoacrylate (AMCRYLATE ; Concord Drugs Ltd.,Hyderabad, India) as an effective therapy for gastric DL without serious complications. In our case study, Isoamyl-2-cyanoacrylate (AMCRYLATE) was effective and safe for treating DL. Surgical wedge resection of the lesion should be considered as a therapeutic option if endoscopic therapy fails.

Modified endoscopic ultrasound-guided selective N-butyl-2-cyanoacrylate injections for gastric variceal hemorrhage in left-sided portal hypertension:A case report

BACKGROUND Left-sided portal hypertension(LSPH),also known as sinistral portal hypertension or regional portal hypertension,refers to extrahepatic portal hypertension caused by splenic vein obstruction or stenosis.N-butyl-2-cyanoacrylate(NBC)has been widely used in the endoscopic hemostasis of portal hypertension,but adverse events including renal or pulmonary thromboembolism,mucosal necrosis and gastrointestinal(GI)bleeding may occur after treatment.Herein,we report successfully managing gastric variceal(GV)hemorrhage secondary to LSPH using modified endoscopic ultrasound(EUS)-guided selective NBC injections.CASE SUMMARY A 35-year-old man was referred to our hospital due to an upper GI hemorrhage.Gastroscopy revealed GV hemorrhage and computed tomography venography(CTV)confirmed LSPH.The patient requested endoscopic procedures and rejected surgical therapies including splenectomy.EUS-guided selective NBC injections were performed and confluences of gastric varices were selected as the injection sites to reduce the injection dose.The“sandwich”method using undiluted NBC and hypertonic glucose was applied.No complications occurred.The patient was followed up regularly after discharge.Three months later,the follow-up gastroscopy revealed firm gastric submucosa with no sign of NBC expulsion and the follow-up CTV showed improvements in LSPH.No recurrent GI hemorrhage was reported during this follow-up period.CONCLUSION EUS-guided selective NBC injection may represent an effective and economical treatment for GV hemorrhage in patients with LSPH.

Endovascular treatment of traumatic direct carotid cavernous fistulas with n-Butyl-2-Cyanoacrylate

Objective To explore the method and safety of endovascular treatment of traumatic direct carotid cavernous fistulas with n-Butyl-2-Cyanoacrylate. Method A total of 11 patients with traumatic direct carotid cavernous fistulas treated by endovascular embolization with n-Butyl-2-Cyanoacrylate. (n-BCA) were retrospectively analyzed,including the

Endovascular embolization of cerebral arteriovenous malformation with N-butyl-2 cyanoacrylate

objective:To explore the characteristics and preparation of N-butyl-2 cyanoacrylate (NBCA) as anembolic material for cerebral arteriovenous malformation (AVM) and to discuss the indications, and technicalnote of transcatheter arterial embolization (TAE) and the prevention of its complications. Methods:Forty patients with AVM were treated using microcatheterization techniques with NBCA through intravascular approach under supervision of digital subtraction angiography (DSA ). Results: of these 40 patients whoseAVMs were ernbolized 57 times, 8 were cured, 31 had significant improvement of clinical symptoms withoutrebleeding. Complications included headache, neurological dysfunction, normal perfusion pressure breakthrough. Intracranial hemorrhage occurred in one case due to rupture of an arterial feeder which required surgical operation. Visual field defect was found and did not recover in one. Conclusion:TAE with NBCA is aneffective therapeutic mesure for AVM. Domestic NBCA is of good quality and low price, therefore, it can beused to substitute for similar imported products.

Synthesis, Crystal Structure, and Herbicidal Activities of 2-Cyanoacrylates Containing 1,3,4-Thiadiazole Moieties

Three series of novel 2-cyanoacrylates 7a--7f, 9a-9f, 10a--10f containing 1,3,4-thiadiazole ring moieties were synthesized as herbicidal inhibitors of photosystem II （PS II） electron transportation. Their structures were clearly verified by lH NMR, 13C NMR, elemental analysis （or HRMS analysis） and single-crystal X-ray diffraction analysis. Bioassay showed that a suitable group at the 3-position of acrylates was essential for high herbicidal activ- ity. In particular, compound 7e showed the best herbicidal activities and gave 100% inhibitory activity against rape and amaranth pigweed at a dose of 1.5 kg/ha. Introduction of substituent with higher polarity such as sulfinyl or sulfonyl to the 5-position of 1,3,4-thiadiazole decreased herbicidal activities.

Endoscopic management of refractory gastrointestinal non-variceal bleeding using Histoacryl(N-butyl-2-cyanoacrylate)glue

Background:Histoacryl glue(N-butyl-2-cyanoacrylate)has well-established utility in the endoscopic management of gastrointestinal variceal bleeding.The role of Histoacryl glue in non-variceal bleeding is less clear,and there are few articles describing its use in this setting.Methods:Six patients with intractable non-variceal gastrointestinal bleeding were managed using injection of Histoacryl glue.All patients had previously failed conventional endostasis and/or interventional angioembolization and were not suitable for emergency salvage surgery due to serious comorbidities or unacceptable anaesthetic risk.An endoscopic Lipiodol-Histoacryl-Lipiodol sandwich injection technique was used in these patients.The clinical outcomes and complications were evaluated.Results:There were four females and two males with a mean age of 55 years.Bleeding lesions included gastric ulcers(n=2),duodenal ulcers(n=2),duodenal gastrointestinal stromal tumor(GIST)(n=1)and rectal ulcers(n=1).All patients had successful Histoacryl endostasis without the requirement for salvage surgery.There was no treatment-related morbidity and no mortality.Two patients had further bleeding after initial Histoacryl endostasis,which was successfully controlled with further endoscopic Histoacryl injection.Conclusion:Histoacryl endostasis should be included in the treatment algorithm for refractory non-variceal gastrointestinal bleeding.

Pulmonary embolism with septicemia after N-butyl-2-cyanoacrylate injection for bleeding gastric varices

Despite many advances in the treatment of gastric variceal bleeding in the two past decades, its management continues to present a clinical challenge. Various treatment modalities have been proposed and since the first report in 1986 endoscopic injection sclerotherapy with cyanoacrylate tissue adhesives has become widely established in many countries as the treatment of choice for bleeding gastric varices. Severe complications of the treatment are infrequent.

Binding Model and 3D-QSAR of 3-（2-Chloropyrid-5- ylmethylamino）-2-cyanoacrylates as PSⅡ Electron Transport Inhibitor

The binding model of 3-（2-chloropyrid-5-ylmethylamino）-2-cyanoacrylate photosystem Ⅱ （PSⅡ） electron transport inhibitors with the D 1 protein of PSII was built. The high herbicidal activity of this kind of inhibitors was explained by docking studies： in addition to usual factors, the N atom on the pyridine ring could form an H-bond with the backbone amide of Phe265 on the D1 protein. 3D-QSAR analysis on sixteen 3-（2-chloropyrid-5-yl- methylamino）-2-cyanoacrylate compounds was performed using CoMFA method to explain the nature of interactions between the compounds and D1 protein. These studies may provide useful insights for designing new PSII electron transport inhibitors.

Proton pump inhibitor administration delays rebleeding after endoscopic gastric variceal obturation

AIM: To clarify the efficacy of proton pump inhibitors (PPIs) after endoscopic variceal obturation (EVO) with N-butyl-2-cyanoacrylate.

Procedure-related complications in gastric variceal obturation with tissue glue

AIM To focus on procedure-related complications,evaluate their incidence,analyze the reasons and discuss the solutions.METHODS Overall,628 endoscopic gastric variceal obturation(EGVO) procedures(case-times) with NBC were performed in 519 patients in the Department of Endoscopy of the Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2016. The clinical data of patients and procedure-related complications of EGVO were retrospectively analyzed.RESULTS In the 628 EGVO procedures,sticking of the needle to the varix occurred in 9 cases(1.43%),including 1 case that used lipiodol-diluted NBC and 8 cases that used undiluted NBC(P = 0.000). The needle was successfully withdrawn in 8 cases. Large spurt bleeding occurred in one case,and hemostasis was achieved by two other injections of undiluted glue. The injection catheter became blocked in 17 cases(2.71%) just during the injection,and 4 cases were complicated with the needle sticking to the varix. Large glue adhesion to the endoscope resulted in difficulty withdrawing the endoscope in 1 case. Bleeding from multiple sites was observed in the esophagus and gastric cardia after the endoscope was withdrawn. Hemostasis was achieved by 1% aethoxysklerol injection and intravenous somatostatin. The ligation device stuck to the varices in two cases during the subsequent endoscopic variceal ligation. In one case,the ligation device was successfully separated from the esophageal varix after all bands were released. In another case,a laceration of the vein and massive bleeding were observed. The bleeding ceased after 1% aethoxysklerol injection.CONCLUSION Although EGVO with tissue glue is usually safe and effective,a series of complications can occur during the procedure that may puzzle endoscopists. There is no standard operating procedure for addressing these complications. The cases described in the current study can provide some reference for others.

Successful endovascular treatment of endoscopically unmanageable hemorrhage from a duodenal ulcer fed by a renal artery: A case report

A 52-year-old woman was admitted with hypovolemic shock. Emergency endoscopy revealed three hemorrhagic duodenal ulcers(all stage A1) with exposed vessels. Two ulcers were successfully treated by endoscopic clipping; however, the remaining ulcer on the posterior wall of the horizontal portion of the duodenum could not be clipped. Because her vital signs were rapidly worsening, we performed transcatheter arterial embolization(TAE) as it is less invasive than surgery. Computed tomography aortography showed that the duodenal hemorrhage was sourced from the lower branch of the right renal artery. In general, the duodenum is fed by branches from the gastroduodenal artery or superior mesenteric artery. However, this patient had three right renal arteries. The lower branch of the right renal artery at the L3 vertebral level was at the same level as the horizontal portion of the duodenum. Complete hemostasis was achieved by TAE using metallic coils and n-butyl-2-cyanoacrylate. After TAE, she recovered from the hypovolemic shock and was discharged from hospital. She has had no recurrence of the hemorrhagic duodenal ulcer for over 1 yr, and followup endoscopy showed no necrosis or stricture of the duodenum. Although she developed a small infarct of her right kidney, her renal function was satisfactory. In summary, the present case is the first reported case of hemorrhagic duodenal ulcer in which the culprit vessel was a renal artery that was successfully treated by TAE. Computed tomography aortography before TAE provides valuable information regarding the source of a duodenal hemorrhage.

Sustained volume decreases in simple renal cysts after sclerotherapy using NBCA with or without hydrodissection

The present study aimed to determine the effectiveness of sclerotherapy using NBCA(Histoacryl Blue(?);B.Braun,Melgungen,Germany),with or without hydrodissection,for the treatment of simple renal cysts.Materials and Methods:Patients who presented to an interventional radiology clinic for the diagnosis of symptomatic renal cysts which had previously been identified at an outpatient clinic were selected for inclusion in this study.A total of 28 patients were randomly divided into 2 groups,based on whether or not they underwent hydrodissection along with ultrasound-guided NBCA-based sclerotherapy.Sonographs were performed at 0,7,and 180 days postprocedure to record the residual volume of the renal cysts and to determine the efficacy of the procedure.Results:A total of 32 cysts in 28 patients were treated with sclerotherapy,18(64%) females and 10(36%) males.The average age of the patients was 61.8 years(range:33-89 years).All patients reported an improvement in symptoms associated with the existing renal cysts at 7 and 180 days post-procedure,and at 7 days post-procedure a statistically significant reduction in cyst volume was observed(all patients:96.8%;group A:96%;group B:97.6%).The reduced cyst volume was still observed 180 days post-procedure(all patients:98.6%;group A:98.2%;group B:98.9%).There was no significant difference between the two treatment groups.Conclusion: There is a significant and persistent reduction in the volume of renal cysts,in addition to an improvement of the associated symptoms,after treatment with NBCA-based sclerotherapy,with or without hydrodissection.

Synthesis and Herbicidal Activity of 2-Cyano-3-methylthio-3-substituted Methylaminoacrylates

A series of 2-cyano-3-methylthio-3-substituted methylaminoacrylates were synthesized as herbicidal inhibitors of photosystem Ⅱ （PSⅡ） electron transport, in order to estimate the effect of fluorine atom, pyridyl group, chirality and ester chain on activity. The important intermediate 2-fluoro-5-aminomethylpyridine was synthesized with high yield. The bioassay results showed that most of rifle compounds had high herbicidal activity in postemergence treatment. The introduction of an a-methyl into the 3-substituted methylamino could improve the activity notably. The replacement of hydrogen by chlorine or fluorine group and phenyl by pyridyl group showed different effects, and at the same time, the ester chain affected the activity too.