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Certain combinations of acidic and basic drugs can cause significant changes in physicochemical properties through the formation of ionic liquids, eutectic mixtures, or deep eutectic solvents. In particular, combining indomethacin and lidocaine is known to result in apparent increases in both the partition coefficients (hydrophobicity) and aqueous solubilities (hydrophilicity). The physicochemical interactions between drugs change the water solubility of the drugs and affect the bio-availability of active pharmaceutical ingredients. Therefore, we need to clarify the mechanism of changes of water solubility of drugs through the physicochemical interactions. In the present study, we identified a thermodynamic factor that regulates the dissolution of a basic drug, in the presence of various acidic nonsteroidal anti-inflammatory drugs. The results demonstrated that enthalpy-entropy compensation plays a key role in the dissolution of drug mixtures and that relevant thermodynamic conditions should be considered.

The purpose of this study is to find that a small amount of 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) can produce a parachute effect on indomethacin (INM). From the examination of dissolution curves and concentration after several days, the supersaturation of INM was observed for the mixtures containing HP-β-CD at a molar ratio ≤ 0.5, and the sustained deployment of supersaturation was found not only in equimolar mixtures but also in mixtures with a shortage of HP-β-CD. In the solid state, it was compared the physical properties of INM/HP-β-CD mixtures using two different mixing methods and determined the stoichiometry of INM and HP-β-CD. Differential scanning calorimetry (DSC) revealed that the polymorphs of INM were converted by HP-β-CD into an amorphous state. Furthermore, X-ray powder diffraction (XRPD) and DSC–XRPD demonstrated that INM crystals from the INM/HP-β-CD mixture prepared from an EtOH solution were metastable. In conclusion, these phenomena may be considered the "spring" and "parachute" effects of mixtures with a shortage of HP-β-CD, as they depended on the presence of the metastable α-form of INM. The addition of 1/3 to 1/20 equivalents of HP-β-CD to INM enhanced INM solubility.

Schwannomas occurring in the gastrointestinal tract are rare, and among them, schwannomas of the large intestine are extremely rare. In this paper, we report a case of a macroscopically atypical schwannoma of the transverse colon. The case is a female aged 67. Stool occult blood test was positive, and colonoscopy revealed a protruded lesion resembling a type 1 carcinoma measuring 4 cm with a reddish and uneven surface on the transverse colon. The surface was smooth and lobulated in observation with indigo carmine spray, and granulation tissue was revealed by biopsies. CT of the abdomen showed an irregular mass, and clinical examinations could not rule out malignancy. Therefore, partial transverse colectomy with peripheral lymph node dissection was performed. Histologically, proliferation of spindle cells was observed originating from the muscularis propria, and most of the upper part of the lesion was replaced by granulation tissue. In immunohistochemical staining, S-100 protein and NSE were positive while KIT, CD34, desmin and smooth muscle actin were negative, and the tumor was therefore diagnosed to be a schwannoma. In addition, since the MIB-1 labeling index was low and virtually no mitosis was observed, it was diagnosed as benign tumor.

Background and Aims: Recently, it was reported that metabolic syndrome (MS) is related to the large \nintestinal neoplasm. Therefore, we studied the relationship between MS and the colonic neoplasm using \nour original scoring system, i.e., the Gastrointestinal Metabolic Syndrome Score(GIMS). Patients and \nMethods: The participants were medical examinees who underwent total colonoscopy (CS) from \nJanuary to December 2006. Regarding body mass index, blood pressure, triglyceride, high density \nlipoprotein cholesterol and fasting blood sugar results in each case,we referred to the criteria of MS and \nscored them from 0-2 (0: normal range, 1: aberration minor, 2: aberration). We added up the values \nto calculate the GIMS. We defined neoplastic lesions as adenoma or adenocarcinoma. When we found \na neoplastic lesion in CS, we examined the case using the GIMS. Results: The average of GIMS in the \nneoplastic cases was significantly higher than that of the non-neoplastic cases(p＜0.05). Considering the \nhigher rate in the efficiency and in the therapeutic patients, we decided that the positive standard was two \nor more scores in GIMS. Conclusions: GIMS is easily calculated and can be used to support diagnosis \nof large intestinal neoplasm in the future.

Utility and safety of EMR for colorectal lesions and lesion-lifted condition as an indicator of the tumor invasion were investigated. We investigated 672 cases and 708 lesions treated between 1993 and 2006. We classified the lesion-lifted condition at the time of submucosal fluid injection, using four categories: "completely lifted/soft", "completely lifted/hard", "incompletely lifted", and "non-lifting". The pit patterns and lifted conditions were related to tumor pathology and the extent of tumor invasion, and often corresponded to particular macroscopic types of tumors. Early colorectal cancer was treated in 231 cases by EMR alone, while 29 cases received additional colectomy after EMR because of an unfavorable pathology. Complications after EMR included bleeding in 19 cases (2.8%) and abdominal pain in 3 (0.4%). There were no cases of perforation. Recurrence occurred in 5 cases (2.2%) (4 cases were cured by re-EMR; one case required surgical resection) out of 231 cancer cases.

A 74-year-old Japanese man was admitted to our hospital due to repeated episodes of upper gastrointestinal\n(GI) bleeding, anemia and melena, which he had suffered for the preceding two years. We\nperformed several panendoscopic and angiographic examinations, but could not discover the cause of his\nanemia. In addition, we performed jejunectomy because arteriovenous malformation (AVM) was\nsuspected to exist in the jejunum. However, we found no evidence of AVM in the resected portion of\nthe jejunum. During an endoscopic GI study on his seventh admission, we found hemorrhaging gastric\nangiodysplasia (AGD) in the upper body of the stomach. Moreover, we found another small AGD in\nthe lower body of the stomach. We treated these lesions endoscopically using a combination of\nhemoclip, endoscopic band ligation and argon plasma coagulation.\nWhen diagnosing patients presenting with the symptoms described herein, the physician should\nconsider small AGDs and check the GI tract accordingly, to prevent unnecessary resections. In the\npresent subject, there has been no further bleeding and no other lesions have been detected in his upper\nGI on endoscopic examination during a 12-month follow up.

The complications with therapeutic colonoscopy reported to date have been associated with the monopolar snare, and the frequency of complications related to use of the bipolar snare is uncertain. This study aimed too investigate the incidence of bleeding and perforation associated with the bipolar snare and to identify the risk factors for bleeding. Between October 2001 and December 2008, all patients with colorectal polyps treated using the bipolar snare were enrolled in this retrospective study. Clinical data were assembled from an electronic database. The incidence of bleeding and perforation was investigated, and the risk factors for bleeding also were determined using multivariate analysis. This study collected 4,719 patients with 10,513 lesions. Perforation occurred for eight patients (0.17%) and bleeding in 66 patients (1.4%). Age younger than 60 years was a significant risk factor for bleeding (P

1100 Incidence of Advanced Neoplasia in Asymptomatic Patients With Diminutive Adenomatous Polyps Detected and Untreated At Initial Screening Colonoscopy Yosuke Otake, Yasuo Kakugawa, Takahisa Matsuda, Chihiro Tsunoda, Yutaka Saito, Yukio Muramatsu, Noriyuki Moriyama Endoscopy division, National Cancer Center Hospital, Tsukiji, Japan; Screening Technology and Development Division, National Cancer Center, Tsukiji, Japan Background and Aim: Effectiveness of colonoscopic removal of adenomatous polyps for prevention of colorectal cancer has been reported and various intervals suggested between colonoscopies after removal of such adenomatous polyps. It is still unclear, however, whether removal of even diminutive adenomatous polyps is necessary. We investigated the incidence of advanced neoplasia in an asymptomatic group in which diminutive adenomatous polyps were detected, but not removed at initial screening colonoscopy and then compared such incidence to the incidence for an asymptomatic group in which no adenomatous polyps were detected at initial screening colonoscopy. Method: We recommend repeat colonoscopy within five years for asymptomatic patients in whom diminutive adenomatous polyps 5mm are detected, but not removed at initial screening colonoscopy as well as for asymptomatic patients without any adenomatous polyps. As for patients in whom larger adenomatous polyps 5mm or cancers are detected, we recommend appropriate therapy. We retrospectively investigated the cumulative incidence of index lesions (ILs) following initial screening colonoscopy in two groups of patients: those without any adenomatous polyps (Group A); and those with adenomatous polyps 5mm (Group B). ILs following initial screening colonoscopy were defined as adenomas 10mm, high-grade dysplasias and cancers. Results: We studied a total of 2,270 asymptomatic patients (1,713 in Group A and 557 in Group B) with a total of 806 diminutive adenomatous polyps detected at initial screening colonoscopy in Group B (1.45 polyps per patient). Median intervals were 59 months and 53 months and cumulative incidences of ILs were 1.0% and 2.2% in Groups A and B, respectively. Cumulative incidence of ILs in Group B was significantly higher compared to Group A (p 0.034) although all 12 detected ILs (two adenomas 10mm, six high-grade dysplasias, three intramucosal cancers and one submucosal cancer with slight invasion) in Group B were successfully treated by endoscopic resection. There were no advanced cancers detected in Group B, but two advanced cancers were detected at follow-up colonoscopies in Group A (not significant). Conclusion: Patients with diminutive adenomatous polyps that were not removed had a significantly higher risk of advanced neoplasia in comparison to patients without any such adenomatous polyps, but invasive cancers requiring surgery or chemotherapy were not detected by followup colonoscopy. It seems unnecessary to remove diminutive adenomatous polyps detected during initial screening colonoscopy of asymptomatic patients, therefore, provided such patients undergo recommended follow-up colonoscopy.