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.

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.

Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

AIM: To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. METHODS: From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. RESULTS: A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). CONCLUSION: A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment.

Hepatitis B virus reactivation in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization therapy.

AIM: The effect of transcatheter arterial chemoembolization (TACE) therapy on hepatitis B virus (HBV) reactivation in hepatocellular carcinoma (HCC) patients with prior resolved hepatitis B is not fully understood. METHODS: From January 2006 to December 2010, 43 hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core antigen (HBc) positive patients with newly diagnosed unresectable HCC were enrolled in the study. All underwent TACE therapy. RESULTS: Four patients (9.3%) developed HBV reactivation with mild/moderate hepatitis. The median number of TACE cycles received was 3.5 (range 3-4 cycles). The median time interval between the occurrence of HBV reactivation and the completion of TACE therapy was 3 months (range 1-5 months) and their median HBV DNA level was 1.58 × 10(4) IU/mL (range, 1.65 × 10(3) -6.42 × 10(4) IU/mL). After the introduction of lamivudine at the occurrence of HBV reactivation, all had resolution of hepatitis. An exploratory analysis indicated that significant predictors of HBV reactivation included increased serum total bilirubin coexisting with cirrhosis and the total number of cycles of TACE received. CONCLUSION: The administration of TACE therapy may increase the risk of HBV reactivation in HBsAg-negative/anti-HBc-positive patients diagnosed with unresectable HCC. Further studies are warranted to explore the optimal management of HBV reactivation in patients with prior resolved hepatitis B.

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.

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.

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.

Life-threatening pseudoaneurysm of the facial artery after dental extraction: successful treatment with emergent endovascular embolization.

Vascular complications after third molar extraction are very rare but may cause a life-threatening situation. The case presented is that of a 25-year-old male who appeared at our emergency department with severe dyspnea and increasing swelling of the left submandibular area 3 days after dental extraction. CT angiography and digital subtraction angiography demonstrated a pseudoaneurysm of the facial artery. Subsequent emergent endovascular embolization with n-Butyl-2-Cyanoacrylate was performed and the patient had a rapid satisfactory resolution.

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.

The use of cyanoacrylates for wound closure in head and neck surgery.

The purpose of this study was to compare the mean duration and complication rates of cyanoacrylate application in head and neck incision closures to those performed with conventional sutures. Eighty patients who underwent head and neck surgical operations (20 thyroidectomies, 13 submandibular gland resections, 9 parotidectomies, 6 neck dissections in conjunction with other surgical procedures, 1 lateral rhinotomy, 1 thyroglossal cyst resection and 30 open neck biopsies) were included in the study. The incisions were closed either with interrupted suture technique (32 patients) or cyanoacrylate (48 patients). The duration of skin closure time was compared between the two groups with nonparametric Mann-Whitney U test and a P value <0.05 was considered as statistically significant. The patients were followed up for complications at 2 weeks, 1 and 3 months after surgery. The two treatment groups were similar with respect to age, gender, and wound lengths (P = 0.27, 0.22 and 0.99, respectively). The mean wound length was 7.21 + 3.15 cm in the cyanoacrylate group and 7.22 + 2.99 cm in the suture group within a range of 5-15 cm. The mean closure time was 33.69 + 9.77 s in the cyanoacrylate group and 504.38 + 169.27 s in the suture group (P < 0.001). The patients in the cyanoacrylate group were satisfied with their scar appearances. No complication was observed in both the groups. Cyanoacrylates provide an easy and convenient application resulting in a faster wound closure as compared to the interrupted suture technique.

Long-term outcomes of acute gastric variceal bleeding in 48 patients following treatment with cyanoacrylate.

OBJECTIVES: (1) Study the effectiveness of intravariceal injection of n-butyl-2-cyanoacrylate to treat acute gastric variceal (GV) bleeding and (2) study the impact of the type of GV and hepatic function on endoscopic hemostasis and mortality outcomes. METHODS: Fourty-eight patients with acute GV bleeding underwent intravariceal injection of n-butyl-2-cyanoacrylate and were followed until death or study conclusion (12-52 months). RESULTS: Primary hemostasis (no re-bleeding within 48 h) was accomplished in 42 patients (87.5%). Appearance of the bleeding site at the time of initial endoscopy, grade of cirrhosis and location of GV were not significant predictors of immediate hemostasis. Early re-bleeding (48 h to 6 weeks) occurred in 20.5% of patients and late re-bleeding (beyond 6 weeks) in 20.5% of patients. While the Child-Pugh score was predictive of re-bleeding and mortality, the type of GV and stigmata at initial endoscopy were not significant predictors of re-bleeding and mortality. Over a mean follow-up of 18 months, mortality rates were 43.9% and bleeding was the commonest cause of death. CONCLUSION: Endoscopic injection of n-butyl-2-cyanoacrylate is effective and safe for treating bleeding GV. Patients with poor hepatic function are at higher risk of re-bleeding and death after acute gastric variceal bleed.

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.

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.

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 percent 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 percent) in contrast with sheep from group S (100 percent); the adhesive remained integral in the uterine tube lumen. The percentual of adherences (66.6 percent) and fibrosis responses (100 percent) was significantly higher in the group L than group AD (0 percent) (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* μm) (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.

OBJETIVO: Avaliar a fertilidade e aspectos macroscópicos, microscópicos e morfométricos da esterilização histeroscópica de tubas uterinas de ovelhas com o adesivo de n-butil-2-cianoacrilato. MÉTODOS: 12 ovelhas adultas, com uma prenhez anterior, foram distribuídas como segue: o grupo L (n=3) submetidas à laparotomia e laqueadura tipo Pomeroy, grupo S (n=3) submetidas à aplicação histeroscópica de solução salina no istmo tubário e grupo AD (n=6), com aplicação histeroscópica de 0,5 ml de cianoacrilato. As ovelhas foram acasaladas com machos de comprovada fertilidade por noventa dias. As ovelhas não prenhes aos 90 dias, foram submetidas à laparotomia com ressecção do útero e tubas uterinas, que foram fixadas em formalina 10 por centos e os cortes histológicos corados em hematoxilina/eosina. Os resultados foram avaliados pelo teste de Wilcoxon e teste exato de Fisher. RESULTADOS: Todas as ovelhas dos grupos L e AD não ficaram prenhes (0 por cento) ao contrário das ovelhas do grupo S (100 por cento); o adesivo permaneceu íntegro no lúmen tubário. O percentual de aderências (66.6 por cento) e de fibrose (100 por cento) foi significativamente maior no grupo L do que no grupo AD (0 por cento) (p<0,01). O diâmetro da porção caudal no grupo AD (2652,15 ± 45,76 μm) foi significativamente maior do que grupo L (1868,27 ± 56.11 mm) (p<0,05). CONCLUSÃO: A inserção histeroscópica do cianoacrilato no lúmen tubário de ovelhas foi eficaz para obstruir a tuba uterina e promover a esterilização.

Pre-operative localization and embolization for jejunal arteriovenous malformation with massive haemorrhage.

Arteriovenous malformation of the gastrointestinal tract is relatively rare in adults. The most accurate diagnosis is by angiography and pre-operative localization has been reported, including by coil embolization, catheter or guidewire replacement, and intraoperative staining techniques. We report the case of a 20-year-old man with acute and massive small intestinal haemorrhage due to jejunal ateriovenous malformation, which was embolized immediately with N-butyl-2-cyanoacrylate. The technique is rapid and safe under fluoroscopy control and the method can help surgeons with mini-laparotomy or laparoscopic surgery because of the clear localization and stable condition of the patient.

The efficacy of N-2-butyl cyanoacrylate in the fixation of nasal septum to the anterior nasal spine in rabbits: experimental study.

In nasal septal surgery, fixing the caudal portion of the nasal septum to the anterior nasal spine is difficult with the present techniques. N-2-butyl cyanoacrylate is a form of cyanoacrylate which is bioabsorbable and biocompatible. The feasibility and efficacy of the compound, which is easy to apply to the tissues, for the above purpose is investigated in this experimental study. Fourteen New Zealand rabbits were included in the study. The nasal septum was exposed with the open approach (transcolumellar). In the study group (n=10), the septum was detached from the nasal floor and attached to a point 3 mm lateral to the nasal spine on the right side, using 2-butyl cyanoacrylate. In control group (n=4) it was deviated 3 mm to the right side and left for spontaneous healing without using any fixation method. Beginning on the third postoperative week, one animal was sacrificed under general anesthesia, every week in the study group and every third week in the control group, and the septum was analysed. Foreign body reaction, histotoxicity, and the structure of the regenerative tissue in the junction of bone and cartilage were analysed with histopathology. The success of stabilization in the study group, where the septum was attached with N-2-butyl cyanoacrylate, was significantly superior to the control group where no fixation method was used (P<0.05). Histopathologically, there were no differences between the two groups with respect to foreign body reaction, histotoxicity, and the tissue that formed between the bone and cartilage (P>0.05). This study demonstrated that N-2-Butyl cyanoacrylate was successful in the fixation of the caudal edge of the nasal septum to the anterior nasal spine. No serious infections, foreign body reaction, necrosis or histotoxicity were observed.