Human Saphenous Vein Histopathology 2 Years After Cyanoacrylate Closure Using the VenaSeal™ System.

There are few long-term histological studies of changes that occur after the treatment of chronic venous disease with cyanoacrylate. In the present study, a histological examination was performed in a 71-year-old man 2 years after he was treated with a VenaSeal™ system. After 2 years, most endothelial cells were destroyed; however, most of the media layer was viable. Moreover, we identified multinucleated giant cells distributed throughout the media layer but found no adventitial infiltration.

Comparison of Short-Term Outcomes Between Endovenous 1,940-nm Laser Ablation and Radiofrequency Ablation for Incompetent Saphenous Veins.

Background: Radiofrequency ablation (RFA) has shown faster recovery and lower pain scores compared to Endovenous laser ablation (EVLA) for treatment of varicose veins. However, a comparison of 1,940-nm EVLA and RFA has not been reported. This study compared short-term outcomes using 1,940-nm EVLA and RFA for varicose veins. Methods: Between April 2018 and June 2018, 43 patients (83 incompetent saphenous veins) were treated with 1,940-nm EVLA and 37 patients (64 incompetent saphenous veins) with RFA. Follow-up duplex was checked at 1 month and 3 months. Results: Baseline characteristics showed no significant differences between both groups except for age. Pain scores at 6 h, and at 1, 10, and 30 days after treatment showed no differences. Complications and time to return to normal activity showed no differences. The 100% closure rate was checked in both groups at 1 month and 3 months follow-up. Conclusion: Short-term outcomes showed no significant differences between 1,940-nm EVLA and RFA treatment.

Photocatalytic degradation of 1,4-dioxane using liquid phase plasma on visible light photocatalysts.

The compound 1,4-dioxane (DO) irritates the eyes, skin, and mucous membrane and is classified as a carcinogen. In this study, the decomposition of DO by photocatalytic reaction using liquid phase plasma (LPP) with photocatalyst was suggested. Plasma was directly discharged as an aqueous DO solution to enhance photocatalytic decomposition activity. To increase the decomposition efficiency of DO by plasma, bismuth ferrite (BFO) prepared by a sol-gel method was introduced as a visible-light photocatalyst. In the application of LPP and BFO photocatalyst, the decomposition of DO by photocatalytic reaction was evaluated. BFO showed UV-vis diffusion reflectance spectroscopy results of absorption of UV and visible light over 600 nm, with a bandgap of approximately 2.2 eV. BFO showed visible light photochemical reaction characteristics to decompose particulate matter (PM) in the irradiation of 6 W visible light LED lamps. It seems that the narrow bandgap of BFO led to the photocatalytic activity in the visible light. In the decomposition reaction of DO with a photocatalyst and LPP, BFO showed better decomposition efficiency than TiO2. BFO can cause photocatalytic reactions in both UV and visible light in the case of LPP irradiation, which emits strong ultraviolet and visible light.

Correlation Between the Immediate Remnant Stump Length and Vein Diameter After Cyanoacrylate Closure Using the VenaSeal System During Treatment of an Incompetent Great Saphenous Vein.

OBJECTIVES: Cyanoacrylate glue is injected for incompetent great saphenous vein (GSV) treatment 5 cm distal to the saphenofemoral junction (SFJ). Although a few reports have investigated the postprocedural remnant stump length, none have focused on the factors affecting glue extension length and the consequent remnant stump length. METHODS: Seventy-nine patients undergoing cyanoacrylate closure using the VenaSeal system at our clinic between August 2018 and November 2018 were investigated. The GSV diameter was measured just before treatment in the supine position 3 cm distal to the SFJ. Cyanoacrylate glue was injected 5 cm distal to the SFJ. RESULTS: The mean glue extension length was 1.13 ± 1.12 cm. The GSV diameter and glue extension length exhibited a significant inversely proportional relationship (P < .001). More specifically, patients with a GSV diameter ≥0.7 cm had a longer remnant stump length than those with a smaller GSV diameter (P < .001). CONCLUSIONS: An increased GSV diameter is likely associated with a decreased glue extension length and, consequently, a longer remnant stump.

Role of stem cell mobilization in the treatment of ischemic diseases.

Stem cell mobilization plays important roles in the treatment of severe ischemic diseases, including myocardial infarction, limb ischemia, ischemic stroke, and acute kidney injury. Stem cell mobilization refers to the egress of heterogeneous stem cells residing in the bone marrow into the peripheral blood. In the clinic, granulocyte colony-stimulating factor (G-CSF) is the drug most commonly used to induce stem cell mobilization. Plerixafor, a direct antagonist of CXCR4, is also frequently used alone or in combination with G-CSF to mobilize stem cells. The molecular mechanisms by which G-CSF induces stem cell mobilization are well characterized. Briefly, G-CSF activates neutrophils in the bone marrow, which then release proteolytic enzymes, such as neutrophil elastase, cathepsin G, and matrix metalloproteinase 9, which cleave a variety of molecules responsible for stem cell retention in the bone marrow, including CXCL12, VCAM-1, and SCF. Subsequently, stem cells are released from the bone marrow into the peripheral blood. The released stem cells can be collected and used in autologous or allogeneic transplantation. To identify better conditions for stem cell mobilization in the treatment of acute and chronic ischemic diseases, several preclinical and clinical studies have been conducted over the past decade on various mobilizing agents. In this paper, we are going to review methods that induce mobilization of stem cells from the bone marrow and introduce the application of stem cell mobilization to therapy of ischemic diseases.

Clinical Features and Management of "Phlebitis-like Abnormal Reaction" After Cyanoacrylate Closure for the Treatment of Incompetent Saphenous Veins.

BACKGROUND: Cyanoacrylate closure for the treatment of incompetent saphenous veins does not cause thermal damage and demonstrates satisfactory outcomes with rapid recovery. However, the characteristics of phlebitis-like abnormal reaction (PLAR), the most common adverse event after cyanoacrylate closure, have not been clarified. Moreover, it differs from typical phlebitis after thermal ablation. The objective of our study is to investigate the clinical features of PLAR after cyanoacrylate closure and to report its management. METHODS: A total of 160 patients with 271 incompetent saphenous veins (great saphenous veins, 201; small saphenous veins, 70) underwent cyanoacrylate closure with the VenaSeal™ system. We defined PLAR as any unusual skin condition that develops suddenly, such as erythema, itching, swelling, and pain/tenderness, over the treated veins several days after cyanoacrylate closure. Oral antihistamines and intravenous dexamethasone were administered to manage PLAR. RESULTS: Of the 271 treated veins, 69 experienced PLAR (25.4%). The mean time of occurrence was 13.6 ± 4.6 days after treatment. The rate of occurrence of erythema, itching, swelling, and pain/tenderness were 92.2%, 91.2%, 66.2%, and 48.5%, respectively. The occurrence of PLAR was significantly higher for great saphenous veins than for small saphenous veins (P < 0.001). Occurrences were more frequent in cases with a suprafascial great saphenous vein of length >10 cm than in cases with a subfascial great saphenous vein (P = 0.001). The proportion of patients who reported swelling decreased by more than half after the administration of oral antihistamine. The pain score on the 10th day also decreased significantly after the administration of antihistamine (P = 0.006). CONCLUSIONS: PLAR must be distinguished from classic phlebitis. We believe that PLAR is a type IV hypersensitivity reaction due to a foreign body, and in our experience, antihistamines or steroids are effective for the prevention and management of PLAR.

Initial outcomes of endovenous laser ablation with 1940 nm diode laser in the treatment of incompetent saphenous veins.

OBJECTIVES: To investigate the initial outcomes of 1940 nm diode laser in the treatment of incompetent saphenous veins. METHODS: This was a prospective observational study. We treated 89 patients with 160 incompetent saphenous veins using a 1940 nm diode laser and bare fiber. The laser's power was set to 4.5 W with a mean linear endovenous energy density of 50.4 J/cm. RESULTS: The one-month closure rate was 100%. The post-procedural pain score at 6 h, 1 day, 10 days, and 1 month was 0.85 ± 1.04, 0.65 ± 1.01, 0.82 ± 1.25, and 0.47 ± 0.82, respectively. Complications encountered included paresthesia (3.8%) and thrombophlebitis (4.4%), whereas no cases of endovenous heat-induced thrombosis were observed. CONCLUSION: The 1940 nm laser and bare fiber at 50.4 J/cm showed satisfactory initial outcomes with less pain and fewer complications, in the treatment of incompetent saphenous veins.

Initial Outcomes of Cyanoacrylate Closure, VenaSeal System, for the Treatment of the Incompetent Great and Small Saphenous Veins.

PURPOSE: Cyanoacrylate closure of the saphenous vein with the VenaSeal system is a new technique just approved on December 2016 in Korea. Therefore, there are seldom reports about postprocedural outcomes of VenaSeal system in Asian countries. We report the initial outcomes of VenaSeal system for the treatment of great saphenous veins (GSVs) and small saphenous veins (SSVs) as a first report in Korea. METHODS: Thirty-four patients with incompetent saphenous veins (47 GSVs and 16 SSVs) were treated at a single session. Concomitant phlebectomy was performed in 15 (44.1%) of 34 patients. All procedures were started with local anesthesia with music therapy and switched to intravenous sedation if patient requested. Patients revisited the clinic on 10 days, 1 month, and 3 months after surgery. Postprocedural evaluations including numerical pain rating score, revised Venous Clinical Severity Scores (rVCSS), and Aberdeen Varicose Vein Questionnaires were checked. Duplex ultrasound was performed on 10 days, 1 month, and 3 months. RESULTS: All treated veins (47 GSVs and 16 SSVs; 100%) had complete closure by duplex ultrasound during the follow-up period. Mean numerical pain rating scale of 6 hours after procedure was 2.7. The rVCSS was improved during the follow-up period. Phlebitis-like "abnormal skin reaction" in the treatment area was occurred in 8 (23.5%) of 34 patients and recovered fully in 2 weeks. CONCLUSIONS: Cyanoacrylate closure, VenaSeal system, is safe and effective for the treatment of incompetent saphenous veins.

Generation, characterization and preclinical studies of a human anti-L1CAM monoclonal antibody that cross-reacts with rodent L1CAM.

L1 cell adhesion molecule (L1CAM) is aberrantly expressed in malignant tumors and plays important roles in tumor progression. Thus, L1CAM could serve as a therapeutic target and anti-L1CAM antibodies may have potential as anticancer agents. However, L1CAM is expressed in neural cells and the druggability of anti-L1AM antibody must be validated at the earliest stages of preclinical study. Here, we generated a human monoclonal antibody that is cross-reactive with mouse L1CAM and evaluated its pharmacokinetic properties and anti-tumor efficacy in rodent models. First, we selected an antibody (Ab4) that binds human and mouse L1CAM from the human naïve Fab library using phage display, then increased its affinity 45-fold through mutation of 3 residues in the complementarity-determining regions (CDRs) to generate Ab4M. Next, the affinity of Ab4M was increased 1.8-fold by yeast display of single-chain variable fragment containing randomly mutated light chain CDR3 to generate Ab417. The affinities (KD) of Ab417 for human and mouse L1CAM were 0.24 nM and 79.16 pM, respectively. Ab417 specifically bound the Ig5 domain of L1CAM and did not exhibit off-target activity, but bound to the peripheral nerves embedded in normal human tissues as expected in immunohistochemical analysis. In a pharmacokinetics study, the mean half-life of Ab417 was 114.49 h when a single dose (10 mg/kg) was intravenously injected into SD rats. Ab417 significantly inhibited tumor growth in a human cholangiocarcinoma xenograft nude mouse model and did not induce any adverse effect in in vivo studies. Thus, Ab417 may have potential as an anticancer agent.

RNA recognition by a human antibody against brain cytoplasmic 200 RNA.

Diverse functional RNAs participate in a wide range of cellular processes. The RNA structure is critical for function, either on its own or as a complex form with proteins and other ligands. Therefore, analysis of the RNA conformation in cells is essential for understanding their functional mechanisms. However, no appropriate methods have been established as yet. Here, we developed an efficient strategy for panning and affinity maturation of anti-RNA human monoclonal antibodies from a naïve antigen binding fragment (Fab) combinatorial phage library. Brain cytoplasmic 200 (BC200) RNA, which is also highly expressed in some tumors, was used as an RNA antigen. We identified MabBC200-A3 as the optimal binding antibody. Mutagenesis and SELEX experiments showed that the antibody recognized a domain of BC200 in a structure- and sequence-dependent manner. Various breast cancer cell lines were further examined for BC200 RNA expression using conventional hybridization and immunoanalysis with MabBC200-A3 to see whether the antibody specifically recognizes BC200 RNA among the total purified RNAs. The amounts of antibody-recognizable BC200 RNA were consistent with hybridization signals among the cell lines. Furthermore, the antibody was able to discriminate BC200 RNA from other RNAs, supporting the utility of this antibody as a specific RNA structure-recognizing probe. Intriguingly, however, when permeabilized cells were subjected to immunoanalysis instead of purified total RNA, the amount of antibody-recognizable RNA was not correlated with the cellular level of BC200 RNA, indicating that BC200 RNA exists as two distinct forms (antibody-recognizable and nonrecognizable) in breast cancer cells and that their distribution depends on the cell type. Our results clearly demonstrate that anti-RNA antibodies provide an effective novel tool for detecting and analyzing RNA conformation.

Surgical targeting of recurrent thyroid cancer using a novel mixture of 99m-technetium macroaggregated albumin and indocyanine green.

BACKGROUND: Precise targeting has played a pivotal role in the success of surgery for recurrent differentiated thyroid cancers (DTCs). To improve on current targeting methods, we developed a novel technique using (99m)Tc-macroaggregated human serum albumin and indocyanine green (TIGMA), with which surgeons effectively target lesions in real time by radiofluorescence dual guidance. METHODS: Seven patients with 10 recurrent DTC lesions were retrospectively enrolled in the study. Prior to the operation, we injected TIGMA into the target lesion under the guidance of ultrasonography. Resection was concurrently monitored using a gamma probe and a specially designed near infrared fluorescence camera. Outcomes were evaluated using imaging, surgical, and pathological records. RESULTS: In all enrolled cases, both injection of TIGMA and radiofluorescence dual guidance were well tolerated and easy to implement. The technical success rates were 100%, confirmed by final pathological examination, postoperative ultrasonography, and I-131 scan clearance. Complications such as temporary postoperative neck pain (n = 2) were minimal. CONCLUSIONS: TIGMA using radiofluorescence dual guidance facilitated the precise targeting of recurrent lesions. The entire procedure was feasible, safe, and successful. This method would help enhance surgical outcomes for recurrent DTCs.

Prognostic Value of Preoperative Serum Levels of Five Tumor Markers (Carcinoembryonic Antigen, CA19-9, Alpha-fetoprotein, CA72-4, and CA125) in Gastric Cancer.

BACKGROUND/AIMS: There is no known specific tumor marker for gastric cancer, although several tumor markers have been used. The aim of this study was to investigate the prognostic significance of preoperative carcinoembryonic antigen (CEA), CA 19-9, alpha-fetoprotein (AFP), CA 72-4, and CA 125 levels in patients with gastric cancer. METHODOLOGY: Medical records of 1,253 patients who were diagnosed with gastric adenocarcinoma were retrospectively reviewed. The clinicopathologic characteristics and disease-free survival rate of the patients were compared between positive and negative CEA, CA 19-9, AFP, CA 72-4, and CA 125 groups of patients. Additionally, the prognostic significance of each tumor marker was assessed by multivariate analysis. RESULTS: CEA, CA19-9, and CA72-4 were more frequently positive in patients with lymphatic and venous invasion, serosal involvement, and lymph node metastasis. The 5-year overall survival and disease free survival rates were significantly associated with elevated serum levels of CEA, CA 19-9, and CA 72-4. The depth of invasion and CA 19-9 were independent prognostic factors. Patients with elevated serum levels of CA 19-9 showed a 3.35-fold higher risk of death than patients with low levels of the marker. CONCLUSIONS: CA 19-9 has prognostic significance in gastric cancer, and a high preoperative serum level of CA 19-9 can be useful for estimating worse prognosis and a higher recurrence of gastric cancer.

Primary mesenteric carcinoid tumor.

Primary mesenteric carcinoid tumor is very rare, although secondary mesenteric involvement is common, reported as 40% to 80%. And distant metastasis rate reported as 80% to 90%, when the size is larger than 2 cm. We present a case of very rare primary mesenteric carcinoid tumor showing benign character though large size. The patient visited St. Vincent's Hospital, The Catholic University of Korea with increasing palpable abdominal mass. At laparotomy, a well encapsulated mass arising from the mesentery near the ligament of Treitz was found without any adjacent organ invasion or distant metastasis. The mass was measured as 8.2 × 7.3 cm and histopathologically benign character. At 11 months of follow up, the patient was recurrence free.

Laparoscopic splenectomy: 3 ports are enough.

With advanced technologies and accumulating experience, a new consensus concerning the least invasive laparoscopic splenectomy should be addressed. We retrospectively analyzed 41 consecutive patients who underwent laparoscopic splenectomy from 1994 to 2007. We divided our patients into 3 groups according to the number of trocars used: group 1 (n=11, 5 trocars), group 2 (n=21, 4 trocars), and group 3 (n=9, 3 trocars). In each group, postural change was made for the operation: supine for group 1, semilateral for group 2, and true lateral for group 3. Except for the shorter operation time for group 3 compared with group 1 and group 2 (P<0.001), there were no differences in perioperative parameters. Considering the least invasive nature of laparoscopic operations, 3-port splenectomy seems to be very promising in this context. Additionally, proper modification of patient's posture is an essential part of the least invasive ever 3-port laparoscopic splenectomy.

Selection of an affinity-matured antibody against a defined epitope by phage display of an immune antibody library.

In a previous study, we generated a murine hepatitis B virus (HBV)-neutralizing monoclonal antibody (mAb), KR127, that binds to an epitope (amino acids 37-45, NSNNPDWDF) of the preS1 antigen. Furthermore, an epitope tag, S1 (NANNPDWDF), was developed for protein tagging. The aim of the present study was to develop a high-affinity antibody to the same preS1 epitope. Mice were immunized with the N-terminal domain of human thrombopoietin fused to the S1 tag (nTPO-S1), and a phage-displayed chimeric Fab library was constructed and screened by panning against nTPO-S1. A high-affinity antibody (3-34) was selected that binds to the preS1 antigen. The IgG molecules of 3-34 showed approximately nine-fold higher affinity (K(D) 1.2 nM) for preS1 compared with KR127 (K(D) 10.4 nM), competed with KR127 for binding to the epitope, and bound to HBV particles. This study provides a simple and efficient way to develop a high-affinity antibody to a defined epitope by phage display of an immune antibody library.