Comparison of 2-Ethyl-Cyanoacrylate and 2-Butyl-Cyanoacrylate for Use on the Calvaria of CD1 Mice

Short-chain cyanoacrylates (SCCA), such as ethyl-2-cyanoacrylate (KrazyGlue, Aron Alpha, Columbus, OH) are commonly used as commercial fast-acting glues. Although once used in clinical medicine as skin adhesives, these products caused tissue toxicity and thus their use in live tissue was discontinued. SCCA were replaced by longer-chain versions (LCCA), such as butyl-cyanoacrylate (Vetbond, 3M, St Paul, Minnesota), which were found to be less toxic than the short-chain formulations. Some researchers prefer to use SCCA due to the belief that they create a stronger bond than do the longer-chain counterparts. In survival surgeries, we compared the bone thickness, bone necrosis, fibrosis, inflammation, and bone regeneration in the calvaria of control (naïve), surgery-only, SCCA-treated, and LCCA-treated mice (n = 20 per group). At 1 and 14 d after surgery, all mice except those treated with SCCA showed statistically similar bone measurements to those of the naive control group. The SCCA group had significantly less bone regeneration than did all other groups. These results suggest that the application of SCCA causes bone damage resulting in the loss of bone regeneration. This finding may assist investigators in choosing a tissue glue for their studies and may support the IACUC in advocating the use of pharmaceutical-grade tissue glues.Abbreviations: LCCA, long-chain cyanoacrylates; SCCA, short-chain cyanoacrylatesCyanoacrylates have been used as tissue adhesives since their synthesis in 1949.⁶ Synthetic cyanoacrylate adhesives belong in the family of liquid monomers formed by alkyl esters of 2-cyanoacrylic acid. The basic formula of the cyanoacrylate adhesive (alkyl-2-cyanoacrylate) has been manipulated to form different cyanoacrylate adhesives with different properties.²⁹ Several 2-cyanoacrylate esters have been synthesized by changing the length of the alkyl chain attached.⁴² The first cyanoacrylates were short-chained, poorly manufactured, and toxic to animals at pharmacologic doses.²⁴ Short-chain cyanoacrylates (SCCA), such as methyl-2-cyanoacrylate and ethyl-2-cyanoacrylate (KrazyGlue [Aron Alpha, Columbus, OH]), continue to be used as fast-acting adhesives.⁵ Although appropriated as tissue glues soon after their discovery, these early SCCA caused tissue toxicity and thus were discontinued in the clinical arena.⁴ Research showed that changing the type of alcohol in the compound to one with a longer molecular chain reduced tissue toxicity. Over time, nontoxic, longer-chain cyanoacrylates (LCCA), such as butyl-cyanoacrylate (Vetbond [3M, St Paul, Minnesota]) and octylcyanoacrylate, were manufactured, leading to their use once again in clinical medicine³³ (Figure 1).Open in a separate windowFigure 1.Trade names for different types of cyanoacrylates.Many researchers contend that SCCA is superior to LCCA in regard to the strength and tenacity of the bond when used to create cranial windows and as an application prior to an overlay of acrylic for cranial implants. However, SCCA is not pharmaceutical-grade, as mandated by the USDA in Policy 3² and the Guide for the Care and Use of Laboratory Animals,²² and therefore can only be used after specific review and approval by an institution''s IACUC. The determination for substitution is generally based on scientific necessity or compound availability.In this study, the effects of applying an SCCA product to mice calvaria were compared with those of an LCCA glue. Specifically, we evaluated bone regeneration, osteocyte numbers, inflammation, and bone remodeling at 2 time points after application. We hypothesized that mice calvaria treated with the SCCA product would show signs of toxicity, compared with skulls treated with the LCCA glue.     

Surgical outcome of synchronous second primary cancer in patients with gastric cancer

PURPOSE: In order to improve the likelihood of curative and safe gastric surgery, this study investigated the clinical features and surgical outcomes of gastric cancer with a synchronous cancer. PATIENTS AND METHODS: The clinicopathological data of 10,090 gastric cancer patients at Samsung Medical Center from September 1994 to December 2006 were retrospectively analyzed. Of them, 90 patients with gastric cancer and a synchronous second primary cancer underwent simultaneous surgery for gastric cancer and second primary cancer. The clinicopathological characteristics of the patients, surgical outcome, and prognosis were examined. RESULTS: The most common synchronous second primary cancer was colorectal cancer (37 patients), followed by hepatocellular carcinoma (13 patients), renal cell carcinoma (11 patients), and pancreatic carcinoma (5 patients). The incidence of a second primary cancer in the gastric cancer patients was higher than the incidence in the general population. Stage I gastric cancer patients had more synchronous cancers than stage II patients (59 vs. 31). Postoperative complications were encountered in 7 patients. Four patients underwent reoperation. Two patients died from hepatic failure and leakage of esophagojejunal anastomosis. The 5-year survival rate of stage I and II gastric cancer was 61% and 39%, respectively. CONCLUSION: Since gastric cancer patients with a synchronous second primary cancer are not rare, the possibility of synchronous cancers in gastric cancer patients should be considered. The prognosis of early stage gastric cancer patients with a synchronous second primary cancer was influenced more by the presence of the second primary cancer than by the gastric cancer itself.     

Multi-disciplinary treatment of a rare pelvic cavity ependymoma

Ependymomas usually develop from neuroectodermal organs. Here, we present an ependymoma arising from the pelvic cavity. A 27-year-old Korean female was admitted to the hospital with a sensation of abdominal fullness. Imaging studies revealed a huge heterogeneous nodular mass in the pelvis and lower abdomen. Laparotomy showed that two large masses with multiple nodules were located between the uterus and rectum and uterus and bladder, respectively. Histologically, the tumor was characterized by compact columnar neoplastic cells divided by fibrovascular septae. The neoplastic cells formed true ependymal rosettes and perivascular pseudorosettes. Immunohistochemical staining showed a strong positive reaction for glial fibrillary acidic protein (GFAP) and vimentin and a partial positive reaction for S100 and EMA. The tumor was thus diagnosed as an ependymoma arising from the pelvic cavity. The patient was treated with a debulking operation and chemotherapy based upon the in vitro chemosensitivity test results. The patient was free of cancer for 4 years following surgery. This is a rare case of extraneural ependymoma for which an in vitro chemosensitivity test was critical in determining the multidisciplinary approach for treatment.     

Standards for Instrument Migration When Implementing Paper Patient-Reported Outcome Instruments Electronically: Recommendations from a Qualitative Synthesis of Cognitive Interview and Usability Studies

Objectives

To synthesize the findings of cognitive interview and usability studies performed to assess the measurement equivalence of patient-reported outcome (PRO) instruments migrated from paper to electronic formats (ePRO), and make recommendations regarding future migration validation requirements and ePRO design best practice.

Prolongation of the period between biopsy and EMR can influence the nonlifting sign in endoscopically resectable colorectal cancers

BACKGROUND: The nonlifting sign is widely used for evaluating the invasion depth of colorectal tumors, and it is commonly accepted that EMR is contraindicated for colorectal tumors with a nonlifting sign because of the probability of massive submucosal invasion. OBJECTIVE: To identify the clinicopathologic factors that affect the nonlifting sign in submucosal invasive colorectal carcinoma (SICC). DESIGN: Details regarding a history of biopsy, postbiopsy days, tumor location, tumor configuration, tumor size, depth of submucosal invasion, histologic type, adenomatous remnants, and angiolymphatic invasion were studied in relation to the nonlifting sign. SETTING: National Cancer Center, Korea. PATIENTS: The study involved 76 patients with SICC treated by endoscopic or surgical resection, in whom the tumor was examined for the nonlifting sign from 2001 to 2006. RESULTS: The nonlifting sign was observed in 15 cases (19.7%). A deep submucosal invasion, a history of biopsy, and the absence of adenomatous remnants were identified as factors affecting the nonlifting sign in univariate and multivariate analyses (P < .05). An increase in the number of postbiopsy days was associated with the nonlifting sign in endoscopically resectable SICC, and all 11 sm1 cancer cases with fewer than 21 postbiopsy days showed lifting. CONCLUSIONS: A history of biopsy and the absence of adenomatous remnants, in addition to deep submucosal invasion, were found to influence the nonlifting sign in SICC. It may be best that mechanical stimulation such as forceps biopsies are minimized before EMR, and EMR should be tried as soon as possible if biopsy was performed.