Adjuvant Transarterial Chemoembolization Following Liver Resection for Intrahepatic Cholangiocarcinoma Based on Survival Risk Stratification.

BACKGROUND: The effectiveness of adjuvant transarterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study was performed to identify ICC patients who would benefit from adjuvant TACE. PATIENTS AND METHODS: The study included 553 patients who underwent hepatectomy for ICC between January 2008 and February 2011 at the Eastern Hepatobiliary Surgery Hospital and who were treated with or without TACE (122 with TACE and 431 without TACE). Survival risk stratification was performed using the established prognostic nomogram (ICC nomogram). The predictive performance was evaluated by concordance index and calibration. The tumor recurrence and overall survival (OS) rates were analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). RESULTS: The predictive performance of the ICC nomogram was demonstrated by the well-fitted calibration curves and an optimal c-index of 0.71 for OS prediction. In the whole cohort, the 5-year recurrence and OS rates between the TACE and non-TACE groups were significantly different (5-year recurrence: 72.9% vs. 78.1%; OS: 38.4% vs. 29.7%). After 1:1 PSM, the TACE and non-TACE groups (122 patients each) had similar 5-year recurrence and OS rates (5-year recurrence: 72.9% vs. 74.2%; OS: 38.4% vs. 36.0%). By survival risk stratification based on ICC nomogram, only the patients in the lowest tertile (nomogram scores ≥77) benefited from adjuvant TACE (TACE vs. non-TACE groups: 90.4% vs. 95.9% for 5-year recurrence; 21.3% vs. 6.2% for 5-year OS). CONCLUSION: Adjuvant TACE following liver resection might be suitable for ICC patients with high ICC nomogram scores (≥77). IMPLICATIONS FOR PRACTICE: The accurate predictive performance of the established prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) following liver resection was reconfirmed in an independent cohort with 553 patients. Based on the survival risk stratification using the nomogram, adjuvant transarterial chemoembolization following liver resection might be suitable only for ICC patients with high scores from the nomogram.

Pharmacokinetic analysis and optimization of hydroxycamptothecin-loaded nanoparticles for liver targeting.

In this paper, a pharmacokinetic model to describe the tissue distribution process of nanoparticles was established. To test the possibility of the model, nanoparticles composed of poly(butylcyanoacrylate) and hydroxypropyl-ß-cyclodextrins (HP-ß-CD) was prepared with a poorly soluble anticancer drug, hydroxycamptothecin (HCPT). Characteristics were determined including particle's size, morphology and in vitro release. The tissue distribution of nanoparticles was also studied. Further, mathematical equation was fitted to the curve of drug concentration-time in liver of hydroxycamptothecin-loaded nanoparticles and the pharmacokinetic parameters of liver were obtained. The effectiveness of hydroxycamptothecin-loaded nanoparticles for liver targeting was evaluated. The results showed that nanoparticles composed of poly(butylcyanoacrylate) and hydroxypropyl-ß-cyclodextrins (HP-ß-CD) exhibited enhanced liver targeting in rats after i.v. injection. More importantly, the pharmacokinetic parameters (transport constant from blood to target organ KT, drug release rate from nanoparticles Kr and drug elimination constant in target organ Ke) provided some quantitative measure of liver distribution and were useful guidelines for development of targeted drug delivery systems.

A case of successful ablation of a gastrophrenic fistula with n-Butyl-2-Cyanocrylate.

A 79-year-old woman with a fistula between a subphrenic abscess and the fundus of the stomach was successfully treated with n-Butyl-2-Cyanoacrylate. Conservative management had failed. Clinical presentation, treatment progress and imaging findings by computed tomography scan, ultrasound, gastroscopy and fluoroscopy are presented, along with a brief review of the relevant literature.

Bedside glue blepharorrhaphy for recalcitrant exposure keratopathy in immobilized patients.

PURPOSE: To report the practical use and the effectiveness of cyanoacrylate glue blepharorrhaphy in immobilized patients with recalcitrant exposure keratopathy. METHODS: Retrospective case series. Temporal two thirds of upper eyelid eyelashes were glued to lower eyelid skin with tissue adhesive n-butyl-2-cyanoacrylate (histoacryl blue) after application of a contact lens. The systemic condition for immobilization; duration of exposure signs in the ocular surface; location, depth, and dimensions of the corneal ulcer; duration of effective blepharorrhaphy; and the time to heal were recorded. RESULTS: Twelve eyes of nine patients were treated. The reasons for immobilization were coma due to malignancy (3 patients), ischemic encephalopathy (2 patients), subarachnoid hemorrhage (2 patients), head trauma (1 patient), coma and hypotony of unknown cause (1 patient). All of the corneal ulcers healed within 4 to 11 days (mean: 5.5 days). Blepharorrhaphy opened spontaneously in 4 to 21 days (mean: 8.6 days). CONCLUSIONS: Bedside glue blepharorrhaphy with tissue adhesive n-butyl-2-cyanoacrylate is a practical, economic, and effective procedure in the treatment of exposure keratopathy in immobilized patients.

Diagnosis and treatment of a superficial upper eyelid arteriovenous malformation.

UNLABELLED: Combined embolization and surgical excision as a safe treatment for a high flow superficial upper eyelid anteriovenous malformation. INTRODUCTION: Orbital arteriovenous malformations (AVM) may cause significant morbidity including chronic pain and cosmetic disfigurement. These rare lesions require a multidisciplinary approach. A case of an orbital high-flow AVM treated subsequently by an mterventional radiologist and oculoplastic surgeon is presented. MATERIALS AND METHODS: Clinical assessment, computed tomography and digital substruction angiography revealed a high-flow AVM. Transvenous and percutaneous embolization was followed by surgical excision. RESULTS: A 1.5 cm, slowly growing, compressible pulsating lesion in the left upper eyelid of a 23 year old man was found. Eye motility and ophthalmologic examination were normal. Valsava manoeuvre didn't increase the size. Imaging revealed a high-flow AVM feeded by the arteria temporalis superficialis (itself feeded by the a. supraorbitalis and supratrochlearis). Draining vessels were the superior ophthalmic vein and a superficial lateral orbital vein. This malformation was first embolized. To prevent iatrogenic embolization of the sinus cavernous, the vein draining into the superior ophthalmic was occluded by a transvenous approach, followed by a percutaneous injection with diluted glue (equal amounts of glubran-2 and lipiodol). The remaining low-flow lesion was then safely excised. CONCLUSION: High-flow orbital AVM represent a considerable treatment challenge. Good cosmetical and functional outcome was obtained safely by subsequent embolization and surgical excision. When treating these rare malformations it is of the highest importance to coordinate the interdisciplinary efforts.

Percutaneous direct puncture glue embolization of high-flow craniofacial arteriovenous lesions: a new circular ring compression device with a beveled edge.

SUMMARY: The purpose of this study was to evaluate the efficacy of a newly designed circular ring compression device that allows safe and effective glue injection during preoperative embolization of high-flow superficial craniofacial arteriovenous malformations (AVMs). The device was used in 4 cases of craniofacial AVM with multiple feeding arteries and draining veins. It provided a safe glue injection route as well as effective compression of radiating multiple venous drainage routes.

Treatment of traumatic cervical arteriovenous fistulas with N-butyl-2-cyanoacrylate.

We report 2 cases of traumatic arteriovenous fistulas in the neck treated with transarterial embolization with n-butyl-2-cyanoacrylate (n-BCA). In both cases, covered stent placement across the fistula to preserve the artery was not possible. Detachable coil placement was attempted in one case but was not successful. Both fistulas were successfully treated with n-BCA embolization. To our knowledge, these are the first 2 such cases reported of high-flow cervical arteriovenous fistulas treated with n-BCA embolization.

Eosinophilic pleural effusion after gastric variceal obliteration with cyanoacrylate.

Pleuropulmonary complications after endoscopic injection sclerotherapy for treatment of esophagogastric varices are not uncommon but are usually mild and self-limited. Herein we report a male patient with liver cirrhosis who underwent endoscopic injection sclerotherapy, using a mixture of n-butyl-2-cyanoacrylate and ethiodized oil for obliteration of gastric varices. After the procedure, he developed moderate amount of left pleural effusion that persisted for a period of time and required thoracentesis and medical treatment. We believed that the inadvertent retrograde reflux of the embolized glue and ethiodized oil via the portosystemic venous collateral into the left pleura might be the possible mechanism for the development of left pleural effusion as the droplets of ethiodized oil were seen along the left pleura on the imaging studies.

Comparison of the bacteriostatic effects, corneal cytotoxicity, and the ability to seal corneal incisions among three different tissue adhesives.

PURPOSE: To compare the bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions among fibrin glue and 2 commercially available cyanoacrylate derivatives: N-butyl cyanoacrylate and methoxypropyl cyanoacrylate. METHODS: The bacteriostatic activities of these tissue glues were verified by measuring the zones of bacterial growth inhibition surrounding the adhesive droplets on agar plates inoculated with Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, or Mycobacterium chelonae. Corneal cytotoxicity was tested by a direct contact method by using cultured bovine corneal epithelial cells, keratocytes, and corneal endothelial cells challenged with droplets of adhesives. Each of the cells was treated with droplets of adhesives. The ability to seal corneal incisions was verified by calculating the maximum intraocular pressure resistant to leakage of rabbit corneal stab wounds sealed with tissue adhesives. RESULTS: Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate showed bacteriostatic effects against S. aureus, S. pneumoniae, and M. chelonae but not P. aeruginosa and E. coli. In contrast, fibrin glue had no such effects against either Gram-positive or -negative bacteria (P < 0.01). Methoxypropyl cyanoacrylate showed the highest levels of corneal cytotoxicity, followed by N-butyl cyanoacrylate. Fibrin glue, however, showed minimal cytotoxicity (P < 0.01). Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate also displayed a greater ability to seal corneal incisions than that of fibrin glue (P < 0.01). CONCLUSIONS: The bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions differed among the 3 compounds tested. These different properties should be considered when choosing tissue adhesives during corneal surgery.

Prevalence of gastric varices and results of sclerotherapy with N-butyl 2 cyanoacrylate for controlling acute gastric variceal bleeding.

AIM: To study the prevalence, predictors and control of bleeding following N-butyl 2 cyanoacrylate (NBC) sclerotherapy of gastric varix (GV). METHODS: We analyzed case records of 1436 patients with portal hypertension, who underwent endoscopy during the past five years for variceal screening or upper gastrointestinal (GI) bleeding. Fifty patients with bleeding GV underwent sclerotherapy with a mean of 2 mL NBC for control of bleeding. Outcome parameters were primary hemostasis (bleeding control within the first 48 h), recurrent bleeding (after 48 h of esophago-gastro-duodenoscopy) and in-hospital mortality were analyzed. RESULTS: The prevalence of GV in patients with portal hypertension was 15% (220/1436) and the incidence of bleeding was 22.7% (50/220). Out of the 50 bleeding GV patients, isolated gastric varices (IGV-I) were seen in 22 (44%), gastro-oesophageal varices (GOV) on lesser curvature (GOV-I) in 16 (32%), and GOV on greater curvature (GOV-II) in 15 (30%). IGV-I was seen in 44% (22/50) patients who had bleeding as compared to 23% (39/170) who did not have bleeding (P < 0.003). Primary hemostasis was achieved with NBC in all patients. Re-bleeding occurred in 7 (14%) patients after 48 h of initial sclerotherapy. Secondary hemostasis was achieved with repeat NBC sclerotherapy in 4/7 (57%). Three patients died after repeat sclerotherapy, one during transjugular intrahepatic portosystemic stem shunt (TIPSS), one during surgery and one due to uncontrolled bleeding. Treatment failure-related mortality rate was 6% (3/50). CONCLUSION: GV can be seen in 15% of patients with portal hypertension and the incidence of bleeding is 22.7%. NBC is highly effective in controlling GV bleeding. In hospital mortality of patients with bleeding GV is 6%.

Clinical-pathological study of the healing of wounds provoked on the dorso-lingual mucosa in 186 albino rats.

OBJECTIVE: To evaluate wound healing of incisions created in the upper aerodigestive tract. STUDY DESIGN AND SETTING: In this prospective and blind study, 186 adult rats were assigned to six groups to create incisions in the tongue. In the first three groups, the wounds were made with a steel scalpel; no substance was applied to the wound in the first group, but N-butyl-2-cyanoacrylate was applied in the second group, and trichloroacetic acid at 50 percent in the third group. In the fourth, fifth, and sixth groups, the wounds were caused by cryosurgery, electrocautery, and CO(2) laser. Hemostasis, postoperative oral intake, and wound healing were measured. Statistical analysis was performed with analysis of variance. RESULTS: The wounds to which N-butyl-2-cyanoacrylate was applied showed no hemorrhaging and faster reepithelialization and resolution of the inflammatory response. CONCLUSIONS: N-butyl-2-cyanoacrylate is a good hemostatic for managing wounds in the oral mucosa provoked by steel scalpel.

Sutureless vascular anastomoses by N-butyl-2 cyanoacrylate adhesive: an experimental animal study.

BACKGROUND: The purpose of this animal study was to find out whether sutureless anastomoses using N-butyl-2-cyanoacrylate were effective in the suppression of neointimal hyperplasia or not. MATERIAL AND METHODS: Ten male adult mongrel dogs were used in this animal study. The animals were randomly divided into a control group (n = 5) and a study group (n = 5). The study group underwent sutureless anastomoses using N-buthyl-2-cyanoacrylate adhesive. Infrarenal aortoaortic graft was interposed using polytetrafluoroethylene. RESULTS: In the study group, the mean intimal thickness at the proximal anastomosis was 27.4 +/- 1.94 microm and 27.4 +/- 1.51 microm at the distal anastomosis. In the control group, the mean intimal thickness was 138.4 +/- 5.02 mum at the proximal anastomosis and 67.6 +/- 6.42 microm at the distal anastomosis. Intimal thickness at the proximal and distal anastomoses in the control group was significantly (p < 0.001) greater than in the study group. Also, perianastomotic inflammation was more obvious in the control group compared to the study group (p < 0.01). CONCLUSION: Sutureless anastomoses using with N-butyl-2-cyanoacrylate adhesive might be a good alternative to conventional suture technique.

Ectopic varices rupture in the gastroduodenal anastomosis successfully treated with N-butyl-2-cyanoacrylate injection.

The term "ectopic varices" is used to describe dilated portosystemic collateral veins in unusual locations other than the gastroesophageal region. We recently experienced a rare case of ectopic varices that developed in the gastroduodenal anastomosis after subtotal gastrectomy. A 70-year-old male with liver cirrhosis due to hepatitis C virus infection was admitted for hematemesis and tarry stool. He had received a subtotal gastrectomy with the Billroth-I method for gastric ulcer at 46 years of age. Although emergency endoscopy revealed esophageal and gastric fundal varices, there were no obvious bleeding points. After removal of the coagula, ectopic varices and a fibrin plug were observed on the gastroduodenal anastomosis. During the observation, blood began to spurt from the fibrin plug. N-butyl-2-cyanoacrylate with lipiodol injection succeeded in hemostasis. Splenic angiography showed gastric varices feeding from a short gastric vein and the posterior gastric vein. The blood flow around the bleeding point, as indicated by lipiodol deposition, had decreased, and no feeding vein was observed. Endoscopic and angiographic findings are shown and the treatment for such lesions is discussed.

[Long-term results of endoscopic histoacryl (N-butyl-2-cyanoacrylate) injection for treatment of gastric varices--a 10-year experience].

BACKGROUND/AIMS: Gastric variceal bleeding is an infrequent but serious complication of portal hypertension. Endoscopic injection of Histoacryl (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 for the treatment of gastric varices. METHODS: Between January 1994 and January 2005, eighty-five patients with gastric varices received endoscopic injections of Histoacryl. 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 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 injection therapy is a effective treatment method for gastric varices with high initial hemostasis rate and low major complications.

[A case of successful endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate for ruptured duodenal varices].

Duodenal varix is a rare cause of hemorrhage in patients with portal hypertension, however their rupture is serious and often life threatening. Treatments for duodenal variceal bleeding include endoscopic procedures, surgery, or interventional radiologic procedures. We report a case of duodenal varices rupture in a 45-year-old man with alcoholic liver cirrhosis who presented with melena and dizziness. Emergent upper endoscopy revealed large nodular varices with a ruptured erosion on the top in the distal second portion of duodenum. Two consecutive injections with 1.0 mL of n-butyl-2-cyanoacrylate (Histoacryl; Braun-Melsungen, Germany) mixed with 1.0 mL of lipiodol (Laboratoire-Guerbet, France) were performed intravariceally and achieved successful hemostasis. This suggests that endoscopic injection sclerotherapy with histoacryl may be an effective therapeutic option for the control of ruptured duodenal variceal bleeding.

Transcatheter arterial embolization with N-butyl-2-cyanoacrylate (Hystoacryl) in two treatments for huge renal arteriovenous malformation.

We report a case of huge renal arteriovenous malformation treated with superselective endovascular embolization in two treatments using N-butyl-2-cyanoacrylate (Hystoacryl).

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 laparotomy 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.

Hysteroscopic sterilization with occlusion of sheep uterine tube using n-butyl-2-cyanoacrylate adhesive.

PURPOSE: To evaluate the fertility and analyze the macroscopic, microscopic and morphometric aspects of sheep uterine tube sterilization with a hysteroscopically insert of n-butyl-2-cyanoacrylate adhesive. METHODS: 12 adult sheep, with one previous pregnancy, were distributed as follows: group L (n=3) subjected to laparotomy and Pomeroy uterine tube ligation, group S (n=3) subjected to hysteroscopic application of saline solution in tube isthmus and group AD(n=6), that was subjected to hysteroscopic application of 0.5 ml of n-2-butil-cyanoacrylate in tube isthmus. They were mated with fertile males for ninety days. The non pregnant sheep, at the 90th day, were subjected to laparotomy with uterus and tubes uterine resection. The fragments of uterine tubes were fixated in 10% formalin and processes for histology evaluated, and slices dyes for H.E. Data were evaluated by Wilcoxon and Mann-Whitney and Fisher's exact test. RESULTS: All sheep from groups L and AD did not get pregnant (0%) in contrast with sheep from group S (100%); the adhesive remained integral in the uterine tube lumen. The percentual of adherences (66.6%) and fibrosis responses (100%) was significantly higher in the group L than group AD (0%) (p<0.01). The diameter of the caudal tube in group AD (2652.15 +/- 45.76 mm) was significantly wider than that of the group L (1868.27 +/- 56.11* microm) (p < 0.05). CONCLUSION: The hysteroscopic insertion of cyanoacrylate in the uterine tube lumen of sheep was effective to obstruct the uterine tube and to promote the sterilization.

Effects of Platelet-Rich Fibrin on Palatal Wound Healing After Free Gingival Graft Harvesting: A Comparative Randomized Controlled Clinical Trial.

This study was conducted to evaluate the effects of platelet-rich fibrin (PRF) on palatal wound healing after free gingival graft (FGG) harvesting. A total of 125 patients were randomized after FGG: PRF with butyl-cyanoacrylate (BC) adhesive (PRF group; n = 42), BC adhesive alone (BC group; n = 42), and sterile wet gauze compression (WG group; n = 41). Bleeding, pain, epithelialization, feeding habits, and sensation scores were recorded for different time points. Statistically significant differences were found for all parameters in favor of the PRF group (P = .0001). PRF may provide significant benefits for wound healing parameters and patients' postoperative course after palatal graft harvesting.

Involvement of bleomycin hydrolase and poly(ADP-ribose) polymerase-1 in Ubc9-mediated resistance to chemotherapy agents.

Ubiquitin-conjugating protein 9 (Ubc9), the sole enzyme for sumoylation, plays critical roles in many physiological functions, such as DNA damage repair and genome integrity. Its overexpression led to poor prognosis and drug resistance in tumor chemotherapy. However, the underlying mechanism by which Ubc9 promotes tumor progress and influences the susceptibility to antitumor agents remains elusive. In this study, we used nine antitumor agents with distinct actions to explore Ubc9-mediated resistance in human breast carcinoma MCF-7 cells. Increase of susceptibility, respectively, to boningmycin, hydroxycamptothecine, cis-dichlorodiamineplatinum, 5-fluorouracil, vepeside and gemcitabine, but not for doxorubicin, vincristine and norcantharidin, was observed after the knockdown of Ubc9 protein level with RNA interference. Reduction of bleomycin hydrolase and poly(ADP-ribose) polymerase-1 levels after knockdown of Ubc9 suggests their contribution to Ubc9-mediated drug resistance. This is the first report on the sensitivity to hydroxycamptothecine, cis-dichlorodiamineplatinum and gemcitabine that increased after knockdown of bleomycin hydrolase at protein level. In conclusion, Ubc9 plays different roles of action in antitumor agents in chemotherapy. The process requires bleomycin hydrolase and poly(ADP-ribose) polymerase-1. The results are beneficial to deeply understanding of Ubc9 functions and for precise prediction of chemotherapy outcomes in tumors.